Evidencepage 2 of 9 · 5070 sources
Bibliography, page 2
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI E-utilities esearch over PubMed and GEO DataSets, run 2026-09-22 by Q98 through a wrapper that refuses any response with an empty querytranslationOncofusion knowledge-graph project (Q98-elongator-smyd3) · NCBI E-utilities 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q96EB1 (ELP4_HUMAN) - Elongator complex protein 4 (hELP4) (PAX6 neighbor gene protein)UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseRefSeq NM_019040.4 - Homo sapiens elongator acetyltransferase complex subunit 4 (ELP4), mRNANCBI RefSeq · NCBI Nucleotide 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.datasetDepMap CRISPR (Chronos) gene-effect scan of 11 KMT2A-rearranged versus 43 other leukaemia lines (this project's own scan)Broad Institute DepMap; joined locally from analyses/depmap-kmt2a-selective-scan-full · analyses/depmap-kmt2a-selective-scan-full 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q8TE02 (ELP5_HUMAN) - reviewed human record, length 300 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q0PNE2 (ELP6_HUMAN) - reviewed human record, length 266 aaUniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryClinicalTrials.gov API v2 query for intervention 'eltanexor'ClinicalTrials.gov · ClinicalTrials.gov 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 42071259Targeting the nuclear export receptor exportin-1 in acute myeloid leukaemia: From biology to clinical translation.Liu Y, Yun X, Ding W, et al. · Clinical and Translational Medicine 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41514668Characterizing KMT2A Rearrangement in Acute Myeloid Leukemia: A Comprehensive Genomic Study.Batayneh O, Moein M, Naji NS, et al. · Cancers (Basel) 2026used by Enasidenib - an approved mutant-IDH2 inhibitor sitting next to the one methylome co-mutation that IS enriched in KMT2A-rearranged AML, and never tested there, IDH and TET2 mutations are mutually exclusive in AML - so 'IDH2 enriched, TET2 depleted' in one cohort is ONE observation, not two, IDH1 - the same oncometabolite, the same assay, and NO enrichment in KMT2A-rearranged AML (6.7% vs 7.6%, p = 0.53): the control that makes the IDH2 result interpretable, IDH2 - the hypermethylating co-mutation that IS enriched in KMT2A-rearranged AML (16.0% vs 10.4%), at p = 0.0004 and not the p < 0.0001 the abstract claims, If the fusion's address requires unmethylated CpG, a hypermethylating co-mutation should be selected AGAINST - and IDH2 is selected FOR, which means the address is not the limiting resource, Is the CpG address a contested resource? On current evidence, no - and the beat that went looking says so, Ivosidenib - the approved IDH1 inhibitor, recorded here so that nobody reaches for it: IDH1 is the paralogue that is NOT enriched in KMT2A-rearranged AML, No IDH inhibitor has ever been reported in KMT2A-rearranged leukaemia: 4 literature records, all reviews, and 1 registry record, an adult master protocol - and the first version of this query returned a false zero, Put mutant IDH2 into SEM and ask three questions at once: does the unmethylated-CpG pool shrink, does the fusion move, and does its competitor move, TET2 is NOT a CXXC protein - its CXXC domain is a separate gene, and it is DEPLETED in KMT2A-rearranged AML rather than enriched, The methylome co-mutation table, recomputed: IDH2 up at p = 0.0004 and not p < 0.0001, IDH1 and DNMT3A flat, and the abstract disagrees with its own Table 2
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.trial_registryA Master Protocol for Biomarker-Based Treatment of AML (The Beat AML Trial)Beat AML, LLC · ClinicalTrials.gov 2026used by Enasidenib - an approved mutant-IDH2 inhibitor sitting next to the one methylome co-mutation that IS enriched in KMT2A-rearranged AML, and never tested there, Ivosidenib - the approved IDH1 inhibitor, recorded here so that nobody reaches for it: IDH1 is the paralogue that is NOT enriched in KMT2A-rearranged AML, No IDH inhibitor has ever been reported in KMT2A-rearranged leukaemia: 4 literature records, all reviews, and 1 registry record, an adult master protocol - and the first version of this query returned a false zero
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseChEMBL molecule record CHEMBL3989908 (ENASIDENIB)ChEMBL, EMBL-EBI · ChEMBL database 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseGTEx v8 median gene expression (TPM) across 54 tissues, gtexportal.org API v2· GTEx Consortium / Broad Institute 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, db=pubmed, run 2026-09-20 with querytranslation inspectedNCBI Entrez Programming Utilities · NCBI E-utilities 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q03111 (ENL_HUMAN) - subcellular location comment with no evidence array, fetched 2026-09-20UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysisanalyses/every-h2ak119ub-number-in-the-corpus/run.py and results.json, this repository; corpus read from git HEAD 2026-09-23; convention values from the committed results of q125-the-h2ak119ub-arm-of-the-pcgf1-knockout and q130-does-the-eviction-gradient-exist-in-h3k79me2Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseFull-text retrieval test across eleven beat papers: Europe PMC core record for PMCID, then fullTextXML, then efetch db=pmc, testing for a body elementOncofusion knowledge graph, Q21 index-fusion-models beat · Europe PMC / NCBI eutils 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed esearch, query: (KMT2A[tiab] OR MLL[tiab]) AND ("fusion partner"[tiab] OR "translocation partner"[tiab] OR "fusion partners"[tiab] OR "translocation partners"[tiab]) AND (prognosis[tiab] OR prognostic[tiab] OR outcome[tiab] OR outcomes[tiab] OR survival[tiab])National Center for Biotechnology Information · PubMed (NCBI E-utilities esearch) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch, db=pubmed: eight subnuclear-compartment queries with query translations inspected, run 2026-09-20Not applicable - database query · NCBI E-utilities 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch and efetch queries for USP2, USP8, MAML2, MAML3, SEPT3/SEPTIN3, SNX9 and menin intersections with MLL/KMT2A, run 2026-09-19National Center for Biotechnology Information (NCBI), PubMed · PubMed (NCBI E-utilities) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch and efetch, queries as stated, with querytranslation inspected and every returned title readNational Library of Medicine · PubMed 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.databaseEurope PMC REST, four-route readability test run 2026-09-19Europe PMC · Europe PMC 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisQ22 phospho-contacts enumeration: kinase-substrate relations on KMT2A and its fusions, with retained/lost calls, bounded rejections and bounded unreadables· Oncofusion knowledge graph (internal enumeration) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseOncofusion knowledge graph, interface-psip1-ibd-kmt2a: LEDGF IBD-KMT2A interface entry, read 2026-09-19· Oncofusion knowledge graph (internal) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q09472 (EP300_HUMAN), Histone acetyltransferase p300· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for EP300 and p300 against KMT2A, MLL and MLL-fusion terms, run for this beat· NCBI PubMed, queried 2026-09-19 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseUniProtKB Q96L91 (EP400_HUMAN), E1A-binding protein p400, 3159 aa· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q96L91 (EP400_HUMAN), SUBCELLULAR LOCATION comment with its full evidence array and TISSUE SPECIFICITY, fetched live 2026-09-21UniProt Consortium · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseIntAct REST findInteractions/Q9Y2J2 (288 indexed interactions), filtered to Q03164/O00255/O75475/Q9UHB7/Q8TEK3/P51825/Q03111/P42568/P55199/P55197 with ac, experimentalRole, detectionMethod, hostOrganism and publicationPubmedIdentifier read per row; retrieved 2026-09-22· IntAct molecular interaction database (EMBL-EBI) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetanalyses/depmap-kmt2a-selective-scan-full/results.json - 17,728 protein-coding genes, 11 Cellosaurus-annotated KMT2A-rearranged versus 43 other leukaemia lines, computed 2026-09-19· DepMap (Broad Institute), via this repository's scan 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC:19876 (EPC1, 'enhancer of polycomb 1') and UniProtKB Q9H2F5 (EPC1_HUMAN)· HGNC / UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q15375 - Ephrin type-A receptor 7 (Homo sapiens), reviewedUniProt Consortium · UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetana-q117-the-published-named-locus-pattern-reproduces-for-meis1-and-jmjd1c-and-breaks-for-mef2c-and-myb (this graph)Iqbal Lab oncofusion knowledge graph, beat Q117 · this project 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P42566 (EPS15_HUMAN), epidermal growth factor receptor substrate 15UniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseInterPro entry-to-protein matches for UniProt P42566InterPro / EMBL-EBI · InterPro 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41265435Inhibition of heme biosynthesis triggers cuproptosis in acute myeloid leukemia.Lewis AC, Gruber E, Franich R, Armstrong J, Kelly MJ, Opazo CM, et al., Kats LM · Cell 2026used by Erythroid progenitor - the committed red-cell precursor, distinct from the bipotent MEP that two entries had to borrow, and the compartment that pays for any haem-pathway or fetal-globin intervention, The OXPHOS-dependent state — established in KMT2A-rearranged AML, and inverted in KMT2A-rearranged B-ALL where OXPHOS inhibition makes leukaemia-initiating cells appear
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P03372 (ESR1_HUMAN), Estrogen receptor· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P03372 (ESR1_HUMAN) SUBCELLULAR LOCATION comment, fetched 2026-09-21· UniProt Consortium 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseENCSR000AHD - CTCF ChIP-seq in MCF-7; optimal IDR thresholded peaks ENCFF942TCG (GRCh38), default_analysis preferred_defaultRichard Myers, HudsonAlpha · ENCODE Portal 2026used by Estradiol does not redistribute SUV39H1 - because the replicates do not agree well enough to see it: over 56,171 CTCF anchors the ACROSS-condition Spearman (0.358) is HIGHER than the within-condition replicate correlations (0.326 for -E2, 0.207 for +E2), and the same 147 bp anchor reads 51.8, 69.1, 90.8 and 96.3 in the four samples, In MCF-7 the two signals point in opposite directions over the same 90 kb: H3K9me3 sits at the 15.8th and 10.3rd percentile of 56,171 same-cell CTCF anchors across the KMT2A gene body (0.82x and 0.65x the random-tile mean) while SUV39H1 sits at the 81.7th-86.8th in all four of its tracks - and the 147 bp anchor carries ZERO H3K9me3 in the minus-estradiol track, The MCF-7 arm, and the clause that saved it: SUV39H1 at the exon-11 anchor reaches the 96.3rd percentile of 56,171 same-cell-type CTCF anchors in one replicate - but all six non-anchor KMT2A intervals are elevated too (medians 73-87), so the pre-registered FIRES clause does not fire, the verdict is NEITHER, and four replicates of one antibody in one cell line span 51.8 to 96.3 at the same 147 bp, Two more independent cell types put the KMT2A exon-11 CTCF summit within 12 bp of the coordinate this graph carries: MCF-7 at chr11:118,488,689 (5 bp away) and SK-N-SH at chr11:118,488,682 (12 bp), both score-1000 optimal-IDR peaks - and in the same tracks the anchor ranks only 72.95th of 56,171 MCF-7 anchors, so it is an unambiguous anchor and an ordinary one
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P41212 (ETV6_HUMAN): reviewed sequence, length and positional feature annotationsUniProt Consortium · UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseAlphaFold Protein Structure Database entry for P41212 (model AF-P41212-F1)Jumper J, Varadi M, et al.; EMBL-EBI/DeepMind · AlphaFold DB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseInterPro member-database domain matches for UniProt P41212 (Pfam, PROSITE, SMART, CDD, CATH-Gene3D, SUPERFAMILY)InterPro Consortium; EMBL-EBI · InterPro 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseSIFTS UniProt residue-level mappings for PDB entries 2DAO, 1JI7, 1LKY, 5L0P (construct ranges read back from the PDBe mappings API)PDBe / SIFTS; EMBL-EBI · PDBe SIFTS 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysisLiterature recall of the Oncofusion knowledge graph against five stated PubMed queries, and the laboratories it never cites· Oncofusion knowledge graph (internal analysis) 2026used by Every age-restricted target nominated by the model is pan-essential or invisible, IGF2BP3 — an RNA-binding protein required for MLL-Af4 leukaemogenesis in mice that CRISPR barely touches in human lines, The 3.7% was mostly the query: DOT1L recall is 19.6% once you ask about leukaemia, We have read a tenth of the recent field, and the gap found a real interactor
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisLineage confound in myeloid transcription-factor dependencies: splitting the KMT2A-rearranged arm (Oncofusion KG analysis)· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysisIs the lineage-consistency ranking a ranking of effect size or of narrowness? (Oncofusion KG analysis)· Oncofusion knowledge graph (internal analysis) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisPower of the DepMap panel to detect a MEN1-scale dependency in rearranged arms (Oncofusion KG analysis)· Oncofusion knowledge graph (internal analysis) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisDoes the MEN1 co-dependency signal survive lineage adjustment? (Oncofusion KG analysis)· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus: search for KMT2A-MLLT1 and individual accession records CVCL_1866, CVCL_8227, CVCL_8485, CVCL_3991, CVCL_6865, CVCL_3937, CVCL_W777Bairoch A, et al.; Cellosaurus · Cellosaurus (SIB) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus cell line records fetched by accession· Cellosaurus (SIB) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetana-kmt2a-exon-to-domain-map (this graph) - Ensembl ENST00000534358 CDS exon boundaries intersected with UniProt Q03164· this project; Ensembl REST; UniProt REST 2026used by Every MS-evidenced KMT2A modification site, flagged retained or lost against the breakpoint - and the retained portion is NOT enriched for acetylation once you use the right null, Which KMT2A exon carries which interface: exon 1 is the menin-binding motif, exons 5-6 are the CXXC zinc finger (computed, not recalled)
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetanalyses/q165-the-retained-acetylation-site/retained-enrichment-null.py· this project 2026used by Every MS-evidenced KMT2A modification site, flagged retained or lost against the breakpoint - and the retained portion is NOT enriched for acetylation once you use the right null, KMT2A K1130 acetylation - the clock-controlled, SIRT1-erased site that every KMT2A fusion retains, 17 residues from the CXXC and 208 from the breakpoint, KMT2A K1130 ubiquitination - the same retained lysine as the clock acetylation site, carrying a chemically exclusive second mark that no KMT2A paper has ever mentioned, KMT2A K1133 acetylation - the better-evidenced half of the pair, and the one that appears in the CBP/p300 acetylome itself, KMT2A K636 acetylation - the forgotten member of the Choudhary quartet, retained, and outside the SIRT1-interaction region, Ranked against four fusion families, the KMT2A acetylation site is the only candidate with no evidence on the fusion at all - and the strongest argument for it is one nobody has made, Resolve acetyl-K1130/K1133 occupancy on the fusion versus wild-type KMT2A in the same cell - the one experiment that makes a shared-sequence site interpretable, The K1130/K1133 numbering is HUMAN, stated in the paper's own words, and the immunising peptide proves it a second time without relying on that sentence, What was searched for a structure and what came back empty: the KMT2A interface layer enumerated by accession pair, with the graph's own unmapped interfaces listed
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseused by Every MS-evidenced KMT2A modification site, flagged retained or lost against the breakpoint - and the retained portion is NOT enriched for acetylation once you use the right null, KMT2A K1235 acetylation - inside the SIRT1-interaction region, retained, and the one member of the Choudhary quartet the source paper named and then never assayed, KMT2A K1364 SUMO - the one modification site inside the breakpoint cluster, retained in some patients' fusion proteins and lost in others, KMT2A K2528 SUMO2 - the single best-supported modification site on the whole protein, in the N320 fragment, and LOST in every fusion, The partner, not the site, is what could make a retained KMT2A modification fusion-specific - the AML1-ETO mechanism asked of KMT2A::AFF1
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysischeck-dangling-data-refs.py output re-analysed by author-cycle provenance and by fuzzy match against the live id set· Oncofusion knowledge graph (internal) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB REST search API, gene_exact queries with fields=accession,id,gene_primary,gene_synonym,protein_name,length, run 2026-09-20UniProt Consortium · UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch and esummary, db=pubmed, run 2026-09-20NCBI · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q01844 (EWS_HUMAN): reviewed sequence, length and positional feature annotationsUniProt Consortium · UniProtKB/Swiss-Prot 2026used by EWSR1 — domain architecture and residue coordinates, EWSR1::ZNF384 - the same EWSR1 exon 7 fragment that drives Ewing sarcoma, fused instead to a zinc-finger protein, in B-ALL, EWSR1::ZNF384 versus EWSR1::FLI1 - the same EWSR1 exon-7 module on two different DNA-binding proteins, and nobody has compared them
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseInterPro/Pfam/CATH-Gene3D/SUPERFAMILY domain matches for UniProt Q01844InterPro Consortium; EMBL-EBI · InterPro 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseEnsembl transcript ENST00000397938 (EWSR1): exon structure and coding-sequence coordinates, used to convert exon breakpoints into residue numbersEnsembl; EMBL-EBI · Ensembl REST API 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseAlphaFold Protein Structure Database entry for Q01844 (model AF-Q01844-F1)Jumper J, Varadi M, et al.; EMBL-EBI/DeepMind · AlphaFold DB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UQ84 (EXO1_HUMAN) - Exonuclease 1, Homo sapiensUniProt Consortium · UniProt Knowledgebase 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI E-utilities esearch over PubMed, db=pubmed, retmode=json, querytranslation read back for every queryNational Center for Biotechnology Information · NCBI Entrez Programming Utilities 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseENCODE Portal experiment search, type=Experiment, assay_title=TF ChIP-seq, status=released, target.label=EXO1ENCODE Project Consortium · ENCODE Portal 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q13015 (AF1Q_HUMAN) Protein AF1q, Homo sapiens, 90 aaUniProt Consortium · UniProtKB 2026used by Experiment: does AF1q self-associate, and does KMT2A::MLLT11 transform? The two measurements nobody has made on the 10th most common KMT2A fusion, KMT2A::MLLT11 (MLL-AF1q), t(1;11)(q21;q23) — 28 patients, and not one functional experiment, MLLT11 / AF1q — a 90-residue protein with no chromatin domain and no oligomerisation module, KMT2A partner in t(1;11)(q21;q23)
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 419802213D Chromosome Remodeling in B-cell Development and Acute Lymphoblastic LeukemiaGhebrechristos YE, Evensen NA, Cathelin RS, et al. · Blood cancer discovery 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q03164 (KMT2A_HUMAN) - canonical sequence, retrieved via the UniProt REST API and scanned for the HBM consensusUniProt Consortium; scan performed for this beat · UniProtKB 2026used by Experiment: put four residues back - the minimal add-back control the PHD3 result has never had, Ledger: every module the KMT2A half loses, with coordinates, how each was confirmed, and whether its loss has been shown to matter, Lost from the KMT2A half: both taspase1 cleavage sites (D2666 and D2718) - the fusion is never processed, Lost from the KMT2A half: PHD2 (aa 1479-1533), an E3 ubiquitin ligase that limits KMT2A's own activity, Lost from the KMT2A half: PHD3 and the bromodomain are one cassette, not two modules (aa 1566-1765), Lost from the KMT2A half: the four-residue HCF-binding motif (DHNY, aa 1799-1802), Lost from the KMT2A half: the FYRN-FYRC clamp (2018-2074 / 3666-3747) that holds wild-type KMT2A together, Lost from the KMT2A half: the SET domain (aa 3829-3945) - the lost module whose loss demonstrably does not matter, Lost from the KMT2A half: the transactivation domain (aa 2829-2883) and its CBP contact, Lost from the KMT2A half: the WIN motif and the whole WRAD interface (aa 3762-3767, Arg3765), The KMT2A N-terminal antibody reports wild-type plus fusion and the C-terminal antibody reports wild-type alone - which makes an N-versus-C difference a fusion-specific readout with no tag and no engineering, The menin that matters in an infant KMT2A-rearranged leukaemia is the menin on the fusion, and the N-minus-C antibody difference can measure it in any patient sample without a tag
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseNegative PubMed search conducted for this graph on 2026-09-19 via the PubMed E-utilities: HCFC1 AND MLL AND leukemia; HCF-1 AND MLL AND transformation AND Hox. Only PMID 15199122 (Yokoyama 2004) and PMID 27009953 (an EBV OriP study) were returned among MLL-relevant hitsQ-subtraction-kmt2a-counter · NCBI PubMed E-utilities 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, counted-absence query for XPO1 inhibition and H3K79Oncofusion Knowledge Graph project (Q61-export-axis) · NCBI E-utilities 2026used by Export or docking? A locus-resolved H3K79me2 ChIP under an XPO1 inhibitor separates the two CALM-AF10 models, and it has never been run, Three measurements the export axis needs and nobody has published: XPO1 occupancy in KMT2A-r, H3K79 under an XPO1 inhibitor, and CRM1 occupancy under a menin inhibitor
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42227701Ziftomenib with venetoclax and azacitidine in relapsed/refractory NPM1-mutated acute myeloid leukemiaWang ES, ... Issa GC · Blood 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.trial_registryClinicalTrials.gov investigator and site records for menin-inhibitor trials in KMT2A-rearranged acute leukaemia, retrieved via the ClinicalTrials.gov API v2US National Library of Medicine · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41438598Targeting dysregulated epigenetic and transcription factor networks in KMT2A-rearranged AML using iPSC models.Palau A; Thier J; Naughton A; Tae-Jun Kwon A; Cabrerizo Granados D; Hofmann S; Kaczkowski B; Zhong X; Lehmann S; Arner E; Lundin V; Lennartsson A · Blood Neoplasia 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC:33738 (EZHIP, 'EZH inhibitory protein') and UniProtKB Q86X51 (EZHIP_HUMAN)· HGNC / UniProt 2026used by EZHIP (CXorf67, CATACOMB) - a protein that jams PRC2 by pretending to be an H3K27M oncohistone, and the 3' payload of MBTD1's other fusion, MBTD1 is the effector-recruiting half of a leukaemia fusion and the addressing half of a sarcoma fusion while donating nearly all of itself to both - so the junction, not the parts, assigns the role
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 42238311CXorf67 in malignancies: Deciphering epigenetic landscapes and clinical implications for precision oncology.Yu X, Wu H, Lan Y, Chen W, Liu J · Genes Dis 2026used by EZHIP (CXorf67, CATACOMB) - a protein that jams PRC2 by pretending to be an H3K27M oncohistone, and the 3' payload of MBTD1's other fusion, Low-grade endometrial stromal sarcoma is a family of NuA4-acetyltransferase-to-Polycomb fusions, and that is why one of MBTD1's two fusions looks nothing like the other, MBTD1::EZHIP (MBTD1-CXorf67), t(X;17)(p11.2;q21.33) - MBTD1's other fusion, in which a NuA4 subunit delivers an H3K27M-mimicking PRC2 poison to low-grade endometrial stromal sarcoma
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasescripts/is-symbol-covered.py run over 2,340 node files (HGNC rows 45,083, retired/alias index 58,536) and NCBI esearch db=pubmed via scripts/pubmed_safe.py, both 2026-09-23. querytranslations read back from each response, e.g. "EZHIP"[Title/Abstract] AND "H3K27me3"[Title/Abstract]. Counts and id lists persisted to analyses/q123-the-architecture-from-other-parts-analogy/bounded-searches.json· oncofusion-knowledge-graph tooling and NCBI PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q0VG06· UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetopenFDA drug/event API query of FAERS for menin-inhibitor endocrine and bone-mineral adverse event termsUS Food and Drug Administration (data); analysis run for this graph, analyses/faers-menin-inhibitor-endocrine/run.py · openFDA FAERS, queried 2026-09-18 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry O15360· UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9BXW9 (FANCD2_HUMAN, Fanconi anemia group D2 protein)· UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9NPI8· UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry O15287· UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9NVI1· UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9NW38· UniProtKB/Swiss-Prot 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q6PCT2 (FXL19_HUMAN), F-box/LRR-repeat protein 19UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseCell Ontology search for pro-B and pre-pro-B terms via the EMBL-EBI Ontology Lookup Service OLS4 APIEMBL-EBI Ontology Lookup Service; Cell Ontology consortium · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCell Ontology (CL) term lookup via the EMBL-EBI Ontology Lookup Service OLS4 APIEMBL-EBI Ontology Lookup Service; Cell Ontology consortium · Database 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42213620The fetal specific gene LIN28B is essential for human fetal B-lymphopoiesis and initiation of KMT2A::AFF1 infant leukemia.Ling RE, Welsh AM, Hamer L, Jackson T, Neil E, Elliott N, et al. · Blood 2026used by Fetal-restricted permissive factors across fusion families - the class has exactly ONE fully worked member, and for ETV6::RUNX1 the fetal advantage is real but no factor is named, LIN28B - a one-row BioID prey of KMT2A that a 2026 Blood paper shows is REQUIRED for KMT2A::AFF1 to transform human fetal cells, LIN28B has THREE published signs in myeloid leukaemia - oncogene, tumour suppressor, and differentiation agent - and the design quality runs opposite to the direction the index-fusion story needs, LIN28B has two routes - blocking let-7, and binding mRNAs directly - and in KMT2A::AFF1 every published mechanism is the direct-mRNA one (let-7 IS measured in mouse MLL-fusion AML: in-session correction), LIN28B-dependent fetal B- and NK-lymphopoiesis - the NORMAL state the leukaemia requirement is parasitic on, and the reason the therapeutic window is narrow by construction, PROPOSED: measure let-7 and restore it in the human fetal-liver KMT2A::AFF1 model - an axis measured in mouse MLL-fusion AML but never in the index fusion, PROPOSED: run a second oncogene in LIN28B-null human fetal liver CD34+ cells - the control that decides whether the KMT2A::AFF1 transformation block is fusion-specific or just a broken progenitor, PROPOSED: swap the partner, hold everything else - KMT2A::MLLT3 versus KMT2A::AFF1 in LIN28B-null human fetal liver CD34+ cells, PUBLISHED, DONE: human fetal liver CD34+ cells fail to transform on KMT2A::AFF1 induction without LIN28B (Ling et al., Blood 2026) - a dedicated human index-fusion experiment, read from the abstract only, Reading the same-source counter-evidence: 77 notes adjudicated, and the defect is not the one the metric measures, Retained fetal programme — the infant-versus-adult stem cell difference, and the reason KMT2A::AFF1 needs no second mutation, Targeting LIN28B - the essential-function and wrong-sign risks are established by the SAME paper that makes it interesting, and the sign may reverse with lineage, The fetal state is PERMISSIVE for lymphoid KMT2A-fusion transformation and PROTECTIVE against myeloid - which is why LIN28B has opposite signs in the two literatures, Two groups invoke LIN28B to explain the SAME epidemiological fact in OPPOSITE directions - and neither claim is the one this graph has been repeating
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42643519Successful treatment of relapsed KMT2A-rearranged AML with central nervous system involvement using revumenib in combination with venetoclax and azacitidine: A case reportXu J, Chen Y, Zhang Y, Zhang F, Zhang Y, Sun J, Xu N · Therapeutic Advances in Hematology 2026used by Fever and headache thirty-two months after transplant: KMT2A::AFDN AML relapsing into the CNS, and a menin inhibitor that cleared the spinal fluid, Menin dependence of a non-elongation KMT2A fusion has never been demonstrated — the counted absence, and what the pivotal trial actually enrolled
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryFHD-286 as Monotherapy or Combination Therapy in Subjects With Advanced Hematologic MalignanciesClinicalTrials.gov, raw API v2 read 2026-09-20 · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryFHD-286 in Subjects With Metastatic Uveal MelanomaClinicalTrials.gov, raw API v2 read 2026-09-20 · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryFHD-286 With Low-Dose Weekly Decitabine/Venetoclax in Patients With Acute Myeloid LeukemiaClinicalTrials.gov, raw API v2 read 2026-09-20 · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus CVCL_2119 (MOLM-13): Sequence variation - Gene fusion KMT2A + MLLT3 (MLL-AF9); FLT3-ITD heterozygous· Cellosaurus (SIB) 2026used by First deposit to put both drug classes on the MEN1 channel in one experiment: VTP-50469 leaves ZERO of the 19 DMSO menin peaks at 15 canonical menin-MLL target loci, while EPZ5676 keeps 14, compound 10 keeps 14 and compound 11 keeps 8 - strength-matched permutation p = 0.0003, and the zero is unchanged at every flank from 0 to 100 kb, In the same deposit, the MENIN inhibitor removes DOT1L from all five DMSO DOT1L peaks at canonical target loci (p = 0.0432) while all three DOT1L inhibitors keep 5/5 - and the VTP DOT1L library still calls ACTB, GAPDH and EEF1A1, which is the internal positive control the MEN1 arm lacks
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseNegative PubMed search: (BioID OR TurboID OR "proximity labeling") AND (KMT2A OR MLL) AND leukemia; and a second query adding interactome and proteomics terms. Both returned 0 results. Conducted for this graph on 2026-09-18 via the NCBI PubMed E-utilitiesOncofusion Knowledge Graph project, using the NCBI PubMed E-utilities · Literature search 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q01543 (FLI1_HUMAN): reviewed sequence, length and positional feature annotationsUniProt Consortium · UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databasePDB 1FLI 'DNA-BINDING DOMAIN OF FLI-1', 5E8G 'Crystal structure of the DNA binding domain of human transcription factor FLI1' and 6VGD 'Crystal structure of the DNA binding domain (DBD) of human FLI1 and the complex of the DBD of human Runx2 with core binding factor beta (Cbfb), in complex with 16mer DNA' (all titles retrieved and verified at RCSB)RCSB Protein Data Bank (entry metadata retrieved and title verified) · RCSB PDB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseEnsembl transcript ENST00000527786 (FLI1): exon structure and coding-sequence coordinates, used to convert exon breakpoints into residue numbersEnsembl; EMBL-EBI · Ensembl REST API 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseAlphaFold Protein Structure Database entry for Q01543 (model AF-Q01543-F1)Jumper J, Varadi M, et al.; EMBL-EBI/DeepMind · AlphaFold DB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseRCSB PDB entries 1RJB, 4XUF, 6JQR and 7ZV9, each verified against the RCSB data API for title, experimental method and resolutionRCSB Protein Data Bank · RCSB PDB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P36888 (FLT3_HUMAN), receptor-type tyrosine-protein kinase FLT3, retrieved via the UniProt REST APIUniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasecBioPortal for Cancer Genomics, study all_stjude_2015 (Acute Lymphoblastic Leukemia, St Jude, Nat Genet 2015) — FLT3 mutation records retrieved via the public REST API on 2026-09-18cBioPortal for Cancer Genomics · Database 2026used by FLT3 in KMT2A-r leukemia — near-universal overexpression, but activating mutation in only ~3% of infants, KRAS as a co-mutation in KMT2A-r leukemia — the single most frequently co-mutated gene, and it still cannot start the disease, NF1 in KMT2A-r leukemia — one homozygous deletion, one missense, and the only loss-of-function co-lesion in the disease, NRAS as a co-mutation in KMT2A-r leukemia — the one co-lesion that is specifically enriched in t(4;11), PTPN11 in KMT2A-r leukemia — named in every gene list, supported by almost no cases, The near-silent genome of infant KMT2A-r ALL — 1.3 non-silent mutations, and why that is bad news as well as good
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42566532MBNL1 hijacks a structured single-stranded distal DNA element to sustain FLT3 expression in KMT2A-rearranged leukemias.Che M, Fields S, et al. · Science advances 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P36888 (FLT3_HUMAN) - subcellular location, fetched 2026-09-20UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41709524Physiologically Based Pharmacokinetic Virtual Twin Approach for Fludarabine Dosing in Pediatric Hematopoietic Stem Cell Transplantation.Mseddi M, Nath C, Ben Hassine K, Mlakar V, Gloor Y, Gonzales F, Uppugunduri CRS, Daali Y, et al. · CPT: Pharmacometrics & Systems Pharmacology 2026used by Fludarabine - the immunosuppressive half of modern conditioning, given as a phosphate prodrug, cleared by the kidney, and dosed by a body-surface-area rule that measurably fails in children, Infants are not small children - four maturing organ systems, three conditioning drugs, and a protocol that treats the first year of life as one category, The fludarabine prodrug chain - three molecules called by one name, and the one that is measured is neither the one given nor the one that works
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC complete set, protein-coding symbols and approved names, used to separate real gene symbols from the uppercase acronyms of a biology corpus· HUGO Gene Nomenclature Committee 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysiscounted-absence-index-recheck: four recorded absences re-run against a second index with positive controls· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 42131930Decoding WDR5-Mediated Interactions in Gliomas: Implications for Targeted TherapyJung E, Piperi C · Medicinal Research Reviews 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProt Q03164 (KMT2A_HUMAN), subcellular location comments for the full-length protein and for the MLL cleavage products N320 and C180· UniProt 2026used by Four hours of MS67 in MV4;11, two KMT2A antibodies: the cheapest test of whether WRAD reaches the fusion or only wild-type KMT2A, The clock/SIRT1-regulated MLL1 acetylation site maps to KMT2A K1130 and K1133 in human numbering, just N-terminal to the CXXC and 208 residues before the breakpoint cluster - so it is retained in every KMT2A fusion, The N-over-C oncoprotein score is not fusion-specific by construction, because taspase1 cleaves wild-type KMT2A into an N320 and a C180 fragment that need not occupy the same chromatin - so a fusion-negative cell has a real N/C signal
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q8TF68 (ZN384_HUMAN) feature table, retrieved live 2026-09-24 by q173· UniProt Consortium 2026used by Four sources give ZNF384 three different zinc-finger counts - 8, 6 and 'five to eight' - and the paralogue's feature table explains where the 6 comes from, Last-exon indels that truncate the ZNF384 C-terminus phenocopy the fusion - so the fusion partner may not be the necessary element, The ZNF384 family is not the inverse of KMT2A::AFF1 - it is the SAME grammar written in the opposite gene order, and three of the four claims in the inverse framing are false, ZNF384 - a C2H2 transcription factor that is the invariant 3' half of a whole B-ALL fusion subtype, including AKAP8::ZNF384
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9H334 (FOXP1_HUMAN), Forkhead box protein P1UniProt Consortium · UniProt 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC record HGNC:3823 (FOXP1) and Ensembl gene ENSG00000114861 on GRCh37 and GRCh38HUGO Gene Nomenclature Committee; Ensembl · genenames.org / Ensembl 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseEnsembl GRCh37 REST: lookup/id/ENSG00000114861?expand=1, per-transcript start coordinates and strandEnsembl · Ensembl GRCh37 archive 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9C0B1 (FTO_HUMAN), human FTO, 505 aa· UniProt Consortium 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseNCBI PubMed esearch, bounded-absence query (counted negative)· NCBI E-utilities 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB - Q8IY81 (SPB1_HUMAN), pre-rRNA 2'-O-ribose RNA methyltransferase FTSJ3· UniProt Knowledgebase 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed entry Q9Y231 (FUT9_HUMAN)UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC record HGNC:4020 (FUT9)HUGO Gene Nomenclature Committee · HGNC 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O60861 (GAS7_HUMAN) Growth arrest-specific protein 7, Homo sapiens, 476 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q99684 (GFI1_HUMAN) SUBCELLULAR LOCATION comment and note, fetched 2026-09-21UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 42418681USP22 is a novel vulnerability regulating MEIS1 protein abundance and gene transcription in KMT2Ar acute leukemiaBröchtel S, Schneider C, Müller M, Villinger C, Plenge T, Gupta MK, et al. (Cremer A, senior author) · Blood 2026used by Giving the reopening conditions an owner, and the first run changes two decisions (run), KAT2A / GCN5 - the SAGA catalytic subunit that reaches this disease through its complex rather than through its own symbol, and whose only chemical tool degrades its paralogue too, MEIS1 — rate-limiting for MLL leukemia stem cells, a surviving co-dependency, and embryonic-lethal when removed, The unnamed KMT2A-rearranged B-ALL line is SEM, and the deposition says KMT2A::AFF1 in a genotype field, USP22 — a KMT2A-rearranged dependency that works through MEIS1 protein stability, and is not an interactor of the fusion
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P00367 (DHE3_HUMAN), Glutamate dehydrogenase 1, mitochondrial — accession, primary gene name, length and subcellular-location comment retrieved 2026-09-24· UniProt Consortium, EMBL-EBI/SIB/PIR 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseNCBI PubMed esearch, bounded-absence query (counted negative)· NCBI E-utilities 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseNCBI eutils esummary db=pubmed (ids 31202577,31202576,28735753,28794467,37788669,34405474), elink dbfrom=pubmed db=pmc id=31202576, esearch db=pmc on the title phrase; and Europe PMC REST search resultType=core by DOI, PMC/31202576/fullTextXML, and BODY: phrase search - all executed 2026-09-22NCBI E-utilities and EMBL-EBI Europe PMC REST · NCBI / Europe PMC 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9NQX3 (GEPH_HUMAN) Gephyrin, Homo sapiens, 736 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q8TD30 (ALAT2_HUMAN), Alanine aminotransferase 2UniProt Consortium · UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI E-utilities esearch db=pubmed: KMT1A[tiab] = 22, KMT1A[tiab] AND KMT2A[tiab] = 0, KMT1A[tiab] AND MLL[tiab] = 0· NCBI PubMed 2026used by GSE139196: SUV39H1 ChIP-Seq in MCF-7 with and without 40 minutes of estradiol - a ligand-inducible SUV39H1 occupancy experiment, filed under the retired symbol KMT1A in its own sample titles, The GEO sweep that q110 named as free and did not run: SUV39H1 chromatin occupancy HAS been measured in two human cell types, six samples, hg38 bigWigs already deposited - so the writer half of the H3K9me3 absence is measured-not-analysed, not never-measured
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetGEO GSE210480 CTCF and H3K9me1 supplementary bigWigs compared by HTTP HEAD Content-Length and by exact per-base array equality over a 5 kb window, 2026-09-22; code and output at analyses/q108-gse210480-h3k9me3-kmt2a-bcr/followups.py and results_followups.json· NCBI Gene Expression Omnibus 2026used by GSE210480 carries FOUR CTCF bigWigs under EIGHT sample accessions, byte-identical, under different filenames - so counting GEO sample records doubled the replicate count and would have halved every standard error, RUN: the eight unreported H3K9me3 samples of GSE210480, read at the KMT2A CTCF element - H3K9me3 does not move where H3K9me1 moves 3.9-fold, and the me1/me2 positive controls passed, What is left after the missing arm was read: there is no H3K9me1, me2 or me3 measurement at the KMT2A breakpoint region in ANY haematopoietic cell, and the founding paper's own archive contains none because all 60 of its samples are epithelial
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysisGEO series GSE299100, sample titles and supplementary filenames enumerated via acc.cgi targ=gsm, fetched 2026-09-23; located by an NCBI GDS search over menin-inhibitor terms returning 112 seriesOncofusion knowledge graph, coordinator · GEO deposit survey, reproducible 2026used by GSE299100 supplies the vehicle-versus-vehicle pair that neither GSE260742 nor GSE127507 could - two independent control hairpins, both DMSO, same date, uniformly processed to hg38_rmdup.tdf, for MEN1, MLL1 and input - in MV4-11, which Cellosaurus confirms carries KMT2A::AFF1 though it presents as monocytic rather than the infant B-ALL this project studies. It also holds MEN1 and MLL1 ChIP under five different menin inhibitors in that line, and the six control files total 1.87 GB, In human KMT2A::AFF1 MV4;11 (monocytic, not B-lineage), the vehicle-versus-vehicle noise floor is 9.4% at the top 0.1% of menin/MLL1 sites and 0.1-2.6% in every other stratum - so cycle 102's borrowed 4-10% band is about right AT THE PEAKS and four to five times too generous everywhere else, and it was applied everywhere
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41399259Targeting IMPDH to inhibit SAMHD1 in KMT2A-rearranged leukaemia.Klootsema Y, Tsesmetzis N, Sharma S, ..., Herold N · Cell Cycle 2026used by Guanine nucleotide supply sustains the LEDGF/menin/MLL-fusion complex - the one place in this graph where metabolism sits UPSTREAM of the menin interface, IMPDH2 - the rate-limiting guanine-nucleotide enzyme whose inhibition lowers LEDGF and menin protein and dismantles the MLL-fusion complex itself, Is the metabolic phenotype a consequence of the fusion programme or an independent dependency? The answer is that BOTH directions are published, and one of them points the other way entirely, Repurposing approved IMPDH inhibitors (mycophenolate, mizoribine, ribavirin) in KMT2A-rearranged leukaemia - cheap, mechanistically attractive, and asking an immunosuppressant of a neutropenic infant, SAMHD1 - the dNTP hydrolase that is the real biomarker behind the IMPDH story, and the reason the KMT2A framing of that story does not hold, The experiment that separates lineage from ontogeny: one KMT2A fusion, two cell-of-origin contexts, three metabolic perturbations, and a limiting-dilution readout alongside the viability one, The myeloid/lymphoid metabolic split in KMT2A-rearranged leukaemia is set by CELL OF ORIGIN (fetal versus adult), not by lineage or by the fusion partner
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41711315IMPDH inhibition enhances cytarabine efficacy in SAMHD1-expressing leukaemia cells via guanine nucleotide depletion.Yague-Capilla M, Dirks C, Eiden C, ..., Rudd SG · Mol Oncol 2026used by Guanine nucleotide supply sustains the LEDGF/menin/MLL-fusion complex - the one place in this graph where metabolism sits UPSTREAM of the menin interface, IMPDH2 - the rate-limiting guanine-nucleotide enzyme whose inhibition lowers LEDGF and menin protein and dismantles the MLL-fusion complex itself, Repurposing approved IMPDH inhibitors (mycophenolate, mizoribine, ribavirin) in KMT2A-rearranged leukaemia - cheap, mechanistically attractive, and asking an immunosuppressant of a neutropenic infant, SAMHD1 - the dNTP hydrolase that is the real biomarker behind the IMPDH story, and the reason the KMT2A framing of that story does not hold
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41191529Guanine nucleotides drive ribosome biogenesis and glycolytic reprogramming in acute myeloid leukemia stem cells.Kawano G, Ikeda R, Ishihara D, ..., Kikushige Y · Blood 2026used by Guanine nucleotide supply sustains the LEDGF/menin/MLL-fusion complex - the one place in this graph where metabolism sits UPSTREAM of the menin interface, IMPDH2 - the rate-limiting guanine-nucleotide enzyme whose inhibition lowers LEDGF and menin protein and dismantles the MLL-fusion complex itself
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseWord-boundary sweep for H2A.Z, H2AZ1, H2AZ2, H2AFZ and H2AFV across nineteen full texts of the core KMT2A-rearranged chromatin literature, retrieved through the PMC HTML and Europe PMC fullTextXML routes and stripped tags-first, entities-second· PubMed Central / Europe PMC 2026used by H2A.Z - two genes of identical length, one KMT2A paper, and the measured quantity is a ratio nobody has repeated, H3.3 - the graph's most-named epigenetic object with no entry, 325 mentions, and not one measurement in a KMT2A-rearranged cell, Rule 80 measured: the abstract index missed the best KMT2A measurement for three marks out of seven, and confirmed the absence for the other four
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P16104 (H2AX_HUMAN), Histone H2AX, 143 aa, primary gene name H2AX, synonym H2AFX· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P0C0S5 (H2AZ_HUMAN), Histone H2A.Z, 128 aa· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC records for H3-3A (HGNC:4764) and H3-3B (HGNC:4765), and the UniProt record P84243 (H33_HUMAN, 136 aa), fetched live 2026-09-20 with gene_primary read back· HUGO Gene Nomenclature Committee / UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB - P68431 (H31_HUMAN), Histone H3.1, and IntAct PSICQUIC MITAB2.7 rows for Q03164, O00255, O75475 and Q9UHB7· UniProt Knowledgebase / EMBL-EBI IntAct 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42424456Degron-independent recruitment of KAT2A expands the target space of CRBN molecular glues.Ojeda S; Wang M; Baek K; Bourgeois W; Sommerschield A; Yue H; et al. · Science 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.preprintPMID 42523331Disrupting a Convergent Acetylation Circuit Collapses Leukemic Identity Across AML Subtypes.Deshpande A; Chiang CY; Perales M; Niranjan N; Sinha N; Finlay D; et al. · bioRxiv 2026used by H3K9ac - the mark KMT2A fusions pile up on their own targets, the one the AF9 reader actually binds, and the one a DOT1L inhibitor strips off first, KAT2A / GCN5 - the SAGA catalytic subunit that reaches this disease through its complex rather than through its own symbol, and whose only chemical tool degrades its paralogue too, KAT2B / PCAF - named in an existing entry's own id and never written, and the only acetyltransferase in this graph whose substrate is a fusion partner protein
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseused by H3K9me1 - the only H3K9 state whose level at the KMT2A breakpoint cluster region has ever been measured, and it is LOW there until KDM3B is removed, H3K9me2 - named sixty times in this graph with no entry of its own, the mark that defines the lamina-associated domains the fusion's targets sit beside, and the only H3K9 methylation state ever measured at a KMT2A fusion's own binding sites
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB Q9Y4C1 (KDM3A_HUMAN, 1,321 aa) FUNCTION comment; resolved by gene_exact:KDM3A AND organism_id:9606 AND reviewed:true returning one row with primary gene name KDM3A· UniProt Consortium 2026used by H3K9me1 - the only H3K9 state whose level at the KMT2A breakpoint cluster region has ever been measured, and it is LOW there until KDM3B is removed, H3K9me2 - named sixty times in this graph with no entry of its own, the mark that defines the lamina-associated domains the fusion's targets sit beside, and the only H3K9 methylation state ever measured at a KMT2A fusion's own binding sites
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseused by H3K9me1 - the only H3K9 state whose level at the KMT2A breakpoint cluster region has ever been measured, and it is LOW there until KDM3B is removed, KDM3B - the H3K9me1/2 demethylase that sits on the KMT2A breakpoint cluster region and keeps it from rearranging, and the only leukaemia gene in this graph whose direction of effect flips between the myeloid and the lymphoid literature
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseused by H3R2me2s - the symmetric mark on the SAME residue as H3R2me2a, which permits rather than enhances WRAD access, and whose 'enhancing' half this graph inherited from the paper that was later revised, H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system, PRMT7 - the enzyme whose class is still disputed, which represses a KMT2 enzyme by writing H4R3me2s, which is required for leukaemia stem cells in CML, and whose only H3R2 claim is the one this beat was dispatched to check
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI PubMed esearch, bounded-absence queries with querytranslation and warninglist recorded· NCBI E-utilities 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q99873 (ANM1_HUMAN) - protein arginine N-methyltransferase 1, FUNCTION comment block, read back 2026-09-22· UniProt 2026used by H4R3me2a - the activating arginine mark that a KMT2-family enzyme's OWN tandem PHD module reads, where the Kabuki-syndrome mutations sit, and which no KMT2A-fusion study has ever measured, PRMT1 — an MLL-fusion cofactor whose first-in-human inhibitor was terminated for lack of efficacy and toxicity
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseused by H4R3me2s - the repressive symmetric arginine mark that recruits DNMT3A, blocks a KMT2 enzyme's own PHD module, and is the ONLY arginine mark ever measured in a KMT2A-fusion system, PRMT5 - the type II arginine methyltransferase this graph has reached for sixteen times, whose mark on H3R2 RECRUITS WDR5 to chromatin
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryA Phase I Study of SNDX 5613 (Revumenib) as Post-Transplant Maintenance After Allogeneic Hematopoietic Cell Transplant in Patients With KMT2A-Rearranged or NPM1-Mutated Acute LeukemiaCity of Hope Medical Center · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseGene Ontology and Cell Ontology term records retrieved via the EBI Ontology Lookup Service (OLS4) APIGene Ontology Consortium; Cell Ontology; EMBL-EBI Ontology Lookup Service · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysiszhou-locus-set-join: this graph's gene entries joined onto Zhou supplemental Table 4, with symbol resolution gated on the project's symbol-collisions registry· Oncofusion knowledge graph (internal analysis) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysisLoad-ranking of unopposed claims in the Oncofusion knowledge graph· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus cell line HB11;19 (CVCL_8227)Bairoch A, et al.; Cellosaurus · Cellosaurus (SIB) 2026used by HB11;19 (CVCL_8227) keeps the YEATS domain and expresses both derivative transcripts - so it is the reciprocal-POSITIVE t(11;19) line, and there is no negative one, The reciprocal MLLT1::KMT2A transcript was reported in the paper that discovered KMT2A, and nobody has gone back to it in thirty-four years
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed counted-absence search for HCFC2 against KMT2A/MLL/menin, run 2026-09-20· PubMed (NCBI) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9Y5Z7 (HCFC2_HUMAN, Host cell factor 2)· UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q13547 (HDAC1_HUMAN), Histone deacetylase 1UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q92769 (HDAC2_HUMAN), Histone deacetylase 2UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O15379 (HDAC3_HUMAN), Histone deacetylase 3UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UQL6 (HDAC5_HUMAN), Histone deacetylase 5UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UQL6 (HDAC5_HUMAN) - SUBCELLULAR LOCATION comment block with evidence codes· UniProt Consortium 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41608562CK2-mediated HDAC5 shuttling regulates DNA end resection through Ku70 deacetylation.Liang X, Zhao J, Li S, Wei R, Yu H, Zhang Q, Fu Q, Qin G, Zhao Y, Liu J, Liu Z, Peng T, Meng J, Gou S, Yin T, Wu H, Wang B, Zhou Y · Theranostics 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.journal-articlePMID 41701111
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB REST search, gene_exact:HDAC7 AND organism_id:9606 AND reviewed:true, with fields accession,id,gene_primary,gene_synonym,protein_name,length; and UniProtKB records Q9UKV0 and Q8WUI4UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026used by HDAC7 - the eraser the index fusion silences, where the proposed therapy is to INDUCE the HDAC, and two 2024-2025 papers point in opposite directions, No HDAC-inhibitor result in this disease attributes to an HDAC enzyme - the only per-enzyme evidence is genetic, and it says the enzyme is not fusion-specific
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UKV0 (HDAC9_HUMAN), Histone deacetylase 9UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UKV0 (HDAC9_HUMAN) - SUBCELLULAR LOCATION comment block with evidence codes· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q7Z4V5 (HDGR2_HUMAN), Hepatoma-derived growth factor-related protein 2, synonyms HDGF2, HDGFRP2, HRP2, 671 aa· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P54198 (HIRA_HUMAN), Protein HIRA, 1017 aa· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P84243 (H33_HUMAN), Histone H3.3, 136 aa, gene names H3-3A; H3-3B· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human entry P04439 (HLAA_HUMAN)UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P04439 (HLAA_HUMAN) SUBCELLULAR LOCATION comment, fetched 2026-09-21· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human entry P01889 (HLAB_HUMAN)UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed entry P01911 (DRB1_HUMAN)UniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetUniProtKB Q16534 (HLF_HUMAN): sequence length, domain, zinc-finger, DNA-binding, repeat, motif and region features, and PDB cross-referencesUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P41235 (HNF4A_HUMAN), Hepatocyte nuclear factor 4-alphaUniProt Consortium · UniProt 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P22626 (ROA2_HUMAN), human HNRNPA2B1, 353 aa· UniProt Consortium 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysisanalyses/is-the-floor-a-property-of-the-mark/run.py and results.json, this repository, computed 2026-09-23 with zero downloads from binned tracks in C:/Temp/q135 and the FLAG DMSO stratifier in C:/Temp/q117; replicate identity and confound structure from analyses/what-the-deposit-says-its-channels-are and the Q135 beatOncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed database queries 'HOTAIRM1 AND leukemia' (23 records) and 'HOTAIRM1 AND leukemia AND MLL AND KMT2A' (0 records), executed 2026-09-18National Library of Medicine, PubMed · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseEnsembl REST API gene lookup, homo_sapiens, assembly GRCh38Ensembl / EMBL-EBI · Ensembl 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseEnsembl REST API gene lookup, homo_sapiens, assembly GRCh38 (release 114)Ensembl / EMBL-EBI · Ensembl 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB - O14980 (XPO1_HUMAN), Exportin-1UniProt Consortium · UniProtKB 2026used by How a lift operator became a postal address: the idea behind the XPO1 axis, in plain language, Two pools of one protein: the chromatin-bound XPO1 that matters here has never been separated biochemically from the soluble export machine, XPO1 / exportin-1 (CRM1) - the cell's main nuclear export receptor, and a chromatin-bound transcriptional scaffold, XPO1 mRNA goes UP when you inhibit the protein - the pharmacodynamic marker that made the paediatric trial interpretable, and what it cannot tell you
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseRCSB PDB entry 1PUF, polymer entity records 1-4; and UniProt REST records P09631, P40424, P31269, P40426RCSB Protein Data Bank; UniProt Consortium; queried by this project 2026-09-20 · Structural and sequence databases 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysisPartner-provenance audit: how much of this graph's mechanism comes from a fusion that is not KMT2A::AFF1· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseChIP-Atlas SUV39H1.5.tsv header: SRX7030945|MCF-7, SRX7030946|MCF-7, SRX7030947|MCF-7, SRX7030948|MCF-7· ChIP-Atlas / DBCLS 2026used by How the three occupancy archives spell zero: ENCODE 404, ReMap 401, ChIP-Atlas 404 - and ChIP-Atlas spells a one-character URL typo exactly the same way, so a whole sweep can come back cleanly and be entirely false, The GEO sweep that q110 named as free and did not run: SUV39H1 chromatin occupancy HAS been measured in two human cell types, six samples, hg38 bigWigs already deposited - so the writer half of the H3K9me3 absence is measured-not-analysed, not never-measured, Three archives, one answer: SUV39H1 has no ENCODE target record under any label (three routes, all empty), ChIP-Atlas's entire hg38 SUV39H1 holding IS the four GSE139196 MCF-7 samples re-indexed, and KMT2A is not among the 26 genes ChIP-Atlas calls SUV39H1 targets
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseEnsembl REST API gene lookup, homo_sapiens, assembly GRCh38 (HOXA-AS2, HOXA-AS3, HOXA3, HOXA5, HOXA6)Ensembl / EMBL-EBI · Ensembl 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed database queries 'HOXA-AS3' (37 records), 'HOXA-AS3 AND leukemia/myeloid' (0 records) and 'HOXA-AS2 AND leukemia' (8 records), executed 2026-09-18National Library of Medicine, PubMed · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P31260 (HXA10_HUMAN) - SUBCELLULAR LOCATION comment block with evidence codes· UniProt Consortium 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42505395Fusion Gene KMT2A::SEPTIN6 in Acute Myeloid Leukemia Cell Line KOPM-88Nagel S, Meyer C, Kaufmann M, Fähnrich S, Rand U, Pommerenke C, MacLeod RAF, Eberth S · Cells 15(14):1286 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseRCSB PDB entry 1PUF polymer-entity records and structure search against UniProt P31269 (zero results), retrieved via the RCSB data and search APIsRCSB Protein Data Bank; UniProt Consortium · Databases 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 42589252Effect of the Proteasome Inhibitor, Bortezomib, on Histone Modifications in Human Leukemic Cell Lines.Sattarifard H, Oyeyode M, Prajapati D, et al. · Int J Mol Sci 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P31269 (HXA9_HUMAN) - subcellular location with evidence codes, fetched 2026-09-20UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P35453, Homeobox protein Hox-D13 (HOXD13)UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetana-q37-the-kmt2a-exon-11-anchor-carries-a-cbx3-and-a-brca1-peak-that-idr-removesQ37-archive-sweep · this graph 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.analysismenin-dna-repair-occupancy: GO DNA repair and homologous recombination gene sets tested against Zhou supplemental Table 4 by permutation· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseNCBI GEO DataSets esearch and analyses/what-the-citation-index-cannot-see/run.py, both run 2026-09-23Q139 · NCBI GEO / Iqbal Lab oncofusion knowledge graph repository 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisanalyses/hunting-the-discarded-spike-in/run.py and results.json, this repository; PMID 31821784 esummary, PMC7227117 full text, and the sample records of GSE127506/127507/137813/137814 all fetched live from NCBI 2026-09-23 and cached alongside the script; SRA runinfo fetched per experimentOncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryClinicalTrials.gov registry query for CBFB-SMMHC / AI-10-49 interventional studies (API v2, query.term=CBFB-SMMHC and AI-10-49): no registered trial of any CBFbeta-SMMHC:RUNX1 interface inhibitor exists as of 2026-09-19.US National Library of Medicine · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O00425 (IF2B3_HUMAN), human IGF2BP3, 579 aa· UniProt Consortium 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41307127A small molecule inhibitor of RNA-binding protein IGF2BP3 shows anti-leukemic activityJaiswal AK, et al. · Haematologica 2026used by Hypothesis: IGF2BP2 and IGF2BP3 buffer each other in KMT2A::AFF1 leukaemia, so single-gene CRISPR under-reports both, I3IN-002 — the first small-molecule IGF2BP3 inhibitor with in vivo activity in an MLL-Af4 model, IGF2BP3 marks the fetal programme AND is required for B-ALL survival - the trap is not expression-for-requirement, it is requirement-for-state-maintenance, IGF2BP3 works in cytoplasmic RNA granules - the only compartment in this beat where a drug is already pointed, and nobody has looked at it in a leukaemia cell
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 41925057Successful Management of Lineage Switch Infant Leukemia With Revumenib and Hematopoietic Cell Transplantation.Granberg RE, Magee JA, Shenoy S, et al. · Pediatr Blood Cancer 2026used by Hypothesis: menin inhibition pushes cells toward the GMP-like state, and the GMP-like state is where menin inhibition works best — so a lineage switch on therapy should predict response, not failure, Lineage switch as a menin-inhibitor escape route — documented in a patient on revumenib, and invisible to every resistance-mutation screen
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryClinicalTrials.gov API v2 search across menin inhibitors, retrieved 2026-09-18US National Library of Medicine, ClinicalTrials.gov · ClinicalTrials.gov 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryTINI 2: Total Therapy for Infants With Acute Lymphoblastic Leukemia IIGruber TA (sponsor-investigator) · ClinicalTrials.gov 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch and Open Targets Platform DepMap query, run 2026-09-20; full counts and name lists in ana-set-nup214-menin-bounded-absence· NCBI PubMed / Open Targets 2026used by Hypothesis: SET::NUP214 activates HOXA partly through recruited wild-type MLL1, which would make a KMT2A-unrearranged leukaemia menin-inhibitor-sensitive, Menin has never been tested against SET::NUP214 - a bounded absence in three independent registers: literature, cell-line dependency data, and the founding paper's own blots, SET::NUP214 is the second KMT2A-free HOXA fusion, and it converges on the same two proteins CALM-AF10 uses: CRM1 and DOT1L - and so does NPM1c, which IS menin-dependent (corrected 2026-09-21), Three addresses, one output: what SET::NUP214 actually does to the menin-interface hypothesis, and why it is a weaker test than CALM-AF10
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42242459Inhibition of MLLT1 Limits Growth of KMT2A::AFF1 Leukemias Without Killing Healthy Hematopoietic Stem Cells.Rajhansa S, Crump NT, Khoo HM, Dopico-Fernandez A, Bozhilov Y, Brennan PE, Fedorov O, Adams C, Farnie G, Milne TA, Wilkinson AC · Experimental Hematology 2026used by Hypothesis: YEATS-pocket occupancy disables the reader module of all three SEC-family complexes in proportion to how much of the reader pool each holds — so the drug's footprint is set by an unmeasured partition, not by the fusion, Scored against the literature: the composition half of the YEATS-selectivity objection holds and the selectivity half is refuted — a scaffold-blind probe already has an in vivo window in the index fusion with no HSPC toxicity, SGC-iMLLT - the MLLT1/MLLT3 YEATS chemical probe, and the 2026 paper that put it into KMT2A::AFF1 in vivo with a healthy-HSPC comparison, The shared reader sits in a complex whose only well-defined normal job is parent-of-origin silencing — and the published safety package for YEATS inhibition is entirely haematopoietic, Two surfaces, two jobs: the AHD picks the scaffold and the YEATS pocket reads the histone — so a YEATS ligand cannot ask which of the three SEC-family complexes it is disabling
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysiscomputed 2026-09-23 from cBioPortal ccle_broad_2025 mutationType joined via DEPMAP_ID to DepMap Chronos (Open Targets GraphQL, dataVersion 26.06), with KMT2A-fusion status from Cellosaurus var:KMT2A AND dr:DepMap; method as in analyses/depmap-arid1b-truncating-stratum-redone/Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026used by I withheld these four numbers last cycle to keep an underpowered contrast out of a narrative, and they point the OTHER WAY: the four truncating-ARID1A leukaemia lines mean -0.0401 against a leukaemia wild-type of -0.0923, a naive +0.0523 where pan-cancer gives -0.2475. And NONE of the four carries a KMT2A fusion, so the intersection this whole thread needs is EMPTY, not merely small, Redone at 11x the power: at n=124 the truncating-ARID1A group IS materially lineage-concentrated (TVD permutation p = 0.00020, against p = 0.42 at n=11), so this time the lineage test had something real to remove - and the effect survives it at -0.2516. The missense null is tight, CI95 (-0.0242, +0.0473), excluding -0.10. And there are now 4 truncating-ARID1A leukaemia lines, one short of testable
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for ICE1 and KIAA0947 against KMT2A, MLL and leukaemia, run for this beat· NCBI PubMed, queried 2026-09-19 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9Y2F5 (ICE1_HUMAN), Little elongation complex subunit 1· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q659A1 (ICE2_HUMAN), Little elongation complex subunit 2· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for ICE2 and its aliases against KMT2A, MLL and leukaemia, run for this beat· NCBI PubMed, queried 2026-09-19 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetIndependent Fisher exact and Wilson-interval recomputation of the KMT2A-altered versus KMT2A-wild-type co-mutation table of PMID 41514668Oncofusion knowledge-graph project, Q81-methylome-axis · Recomputed 2026-09-21 from percentages read out of PMC12784994 Table 2; counts back-calculated as round(pct x n), accurate to about one case 2026used by IDH1 - the same oncometabolite, the same assay, and NO enrichment in KMT2A-rearranged AML (6.7% vs 7.6%, p = 0.53): the control that makes the IDH2 result interpretable, IDH2 - the hypermethylating co-mutation that IS enriched in KMT2A-rearranged AML (16.0% vs 10.4%), at p = 0.0004 and not the p < 0.0001 the abstract claims, The methylome co-mutation table, recomputed: IDH2 up at p = 0.0004 and not p < 0.0001, IDH1 and DNMT3A flat, and the abstract disagrees with its own Table 2
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O75874 (IDHC_HUMAN), Isocitrate dehydrogenase [NADP] cytoplasmicUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human entry P15260 (INGR1_HUMAN)UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42380666Lineage-restricted dependency on an oncofetal SNHG29-IGF2BP1 RNA axis in acute megakaryoblastic leukemiaWinkler R, et al. · Leukemia 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9NZI8 (IF2B1_HUMAN), human IGF2BP1, 577 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9Y6M1 (IF2B2_HUMAN), human IGF2BP2, 599 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O00425 (IF2B3_HUMAN) - subcellular location with evidence codes, fetched 2026-09-20UniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetQ147 pre-registration - FLOOR-B and the decision not to use IgG as the gateIqbal Lab oncofusion knowledge graph, beat Q147 · this project 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry O14920 (IKKB_HUMAN), Inhibitor of nuclear factor kappa-B kinase subunit betaUniProt Consortium · UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, db=pubmed, run 2026-09-20NCBI · PubMed 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, db=pubmed, run 2026-09-20NCBI · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9Y6K9 (NEMO_HUMAN), NF-kappa-B essential modulatorUniProt Consortium · UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, db=pubmed, run 2026-09-20NCBI · PubMed 2026used by IKK/NF-kB retains MLL on chromatin — BOTH the fusion and wild-type MLL, at two promoters, in mouse myeloid AML, and it is occupancy loss rather than protein loss, The NF-kB story in KMT2A-rearranged leukaemia is a myeloid story, and the lymphoid half is not a weaker version of it — it is a different subject
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41419607Targeting IL-1/IRAK1/4 signaling in acute myeloid leukemia stem cells following treatment and relapse.Ho TC, LaMere MW, ... Becker MW · Leukemia 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, db=pubmed, run 2026-09-20NCBI · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P26951 (IL3RA_HUMAN), Interleukin-3 receptor subunit alpha, 378 aa, single reviewed human record, primary gene name IL3RA· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetanalyses/depmap-kmt2a-selective-scan-full/results.json - 17,728 protein-coding genes, 11 Cellosaurus-annotated KMT2A-rearranged versus 43 other leukaemia lines, computed 2026-09-19· DepMap (Broad Institute), via this repository's scan 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P12268 (IMDH2_HUMAN), Inosine-5-prime-monophosphate dehydrogenase 2UniProt Consortium · UniProt 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseIntAct PSICQUIC, MITAB2.7 rows for Q03164, O00255, O75475, Q9UHB7 and P51825, filtered on the twelve read-queue accessions· EMBL-EBI IntAct 2026used by In all 24 read-queue rows inspected, the candidate is the BAIT and this project's protein is the prey - nobody has ever tagged KMT2A, AFF4, menin or PSIP1 and found any of them; plus seven bounded rejections, PES1 / pescadillo (O00541) - the missing PeBoW subunit of this graph's nucleolar block, pan-essential in 96.9% of DepMap lines, and the one myeloid experiment on it shows proliferation WITHOUT a differentiation block, RSBN1 / KDM9 (Q5VWQ0) - an H4K20me2/me3 demethylase in the AFF4 proximity record, and the only read-queue partner that is a chromatin enzyme at all, The interactome coverage figure is computed on 651 of the 1,015 IntAct rows available - 64% - and the gap is worst for menin and LEDGF, the two baits the menin-interface hypothesis rests on
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUCSC Genome Browser API, hg19 cpgIslandExt track - 30,344 islands, 27,537 on chr1-22 and chrX, fetched 2026-09-23· UCSC Genome Browser 2026used by In human RS4;11 (KMT2A::AFF1), menin occupancy at its own top 0.1% of 2 kb bins falls 14.9x to 2.0x over the track median and its share of total coverage falls to 0.200 - reproducing Q117's murine FLAG-MLLAF9 figures (15.9x to 3.0x, ratio 0.179) to within 1.3-fold on all five statistics, Q117's CpG-island falsifier reproduces in the human index fusion almost to the decimal - gained bins 5.66% on an island against a class-matched null of 4.23%, fold 1.34, Fisher p = 0.49, where Q117 got fold 1.35 and p = 0.53 - so the CXXC-redistribution model fails in human RS4;11 as it did in mouse
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseBounded PubMed absence for alternative lengthening of telomeres in KMT2A-rearranged and lymphoblastic leukaemia, run through scripts/pubmed_safe.py· PubMed (NCBI E-utilities), via this project's pubmed_safe wrapper 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysisanalyses/arid1a-kmt2a-cooccurrence-in-patients/run.py and results.json, this repository; cBioPortal studies aml_stjude_2024 and all_phase2_target_2018_pub, queried 2026-09-23; KMT2A entrez 4297 verified against /api/genes before useOncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetQ154 label permutation over the published GSE252378 oncoprotein-target call tableIqbal Lab oncofusion knowledge graph, beat Q154 · this project 2026used by In the deposit paper's own target-gene table, the AFF1-exclusive class is 64 genes against a permutation null of 2.3, and it survives call-rate matching, institution stratification, B-lineage restriction and patient collapse, IRX1's own three-sample pattern is p = 0.022 naively and 0.077-0.176 once patients, institution or lineage are held fixed - the class it belongs to is significant, IRX1 alone is not, KMT2A-N/C CUT&RUN on one untreated KMT2A::AFF1 blast from outside Texas Children's, scored at the six AFF1-exclusive gene bodies with a pre-declared margin column
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetQ154 pre-registration, written before computationIqbal Lab oncofusion knowledge graph, beat Q154 · this project 2026used by In the deposit paper's own target-gene table, the AFF1-exclusive class is 64 genes against a permutation null of 2.3, and it survives call-rate matching, institution stratification, B-lineage restriction and patient collapse, IRX1's own three-sample pattern is p = 0.022 naively and 0.077-0.176 once patients, institution or lineage are held fixed - the class it belongs to is significant, IRX1 alone is not
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 40898981Off-the-shelf dual CAR-iNKT cell immunotherapy eradicates medullary and leptomeningeal high-risk KMT2A-rearranged leukemia.Ren H, Elliott N, Lye B, Sharif Shohan MU, Cross JW, Field L, et al. · Blood 2026used by In this fusion family, MHC class I is not silenced - it is elevated and load-bearing, holding NK cells off the leukaemia stem cell, The CNS-adapted state — leukaemia-propagating cells reprogrammed by the central nervous system niche, and worse at restarting systemic disease afterwards, The NK cell - the effector arm of haploidentical transplant, the one this disease is documented to evade, and the cell CLEC12A was named on, Thomas Milne (MRC WIMM, Oxford) — MLL-AF4 target biology, enhancer architecture and PROM1/CD133
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisanalyses/what-this-corpus-actually-cites/add_abstracts.py and abstract-coverage.json, this repository, computed 2026-09-24 with abstracts fetched live from PubMed efetch in batches of 180Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisanalyses/what-deposits-this-corpus-actually-cites/run.py, results.json and deposit-index.json, this repository, computed 2026-09-24 against the committed node files with series records fetched live from the GEO accession endpointOncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisanalyses/what-this-corpus-actually-cites/run.py, results.json and citation-index.json, this repository, computed 2026-09-23 against the committed node files with titles fetched live from PubMed esummaryOncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026used by Indexing every PMID in every entry - CORRECTED to 4,000 distinct papers across 2,411 entries after the original regex was found to miss 73.7% of them by matching prose but not the schema's own citation field, an undercount that made this entry declare a gap the corpus refuted 14 times over, The citation index built to stop false gap claims made one: its regex matched prose but not the schema's own pmid field, missing 73.7% of the corpus's citations, and the single-cell gap it selected was refuted by a paper already cited in fourteen entries
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetNCBI GEO GSM8123359 (MLLAF9 Control - DMSO FLAG) annotated against UCSC mm10 refGene via api.genome.ucsc.edu, 2026-09-23· NCBI Gene Expression Omnibus / UCSC Genome Browser 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUCSC Genome Browser API, list/chromosomes for mm10 and mm39, fetched 2026-09-23· UCSC Genome Browser 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseIntAct REST findInteractor (mll_af9, mll_enl, mll_aff4_fusion, EBI-2620048, EBI-2620075) and findInteractions for each accession, with interactorXrefs, interactorPreferredIdentifier, interactionCount, experimentalRole, detectionMethod, hostOrganism and publicationPubmedIdentifier read per record; retrieved 2026-09-22· IntAct molecular interaction database (EMBL-EBI) 2026used by IntAct curates 47 interactions against engineered MLL fusion proteins, and every accession-keyed query in this project is blind to all of them - while its PSICQUIC mirror stops at 2024, MED19 - the Mediator subunit curated against an engineered MLL-AFF4 fusion protein, and the one REST uses to deliver G9a, The federated sweep this graph prescribes for the missing index-fusion interactor cannot be run: PSICQUIC free text returns ZERO for `mll_af9`, an entity that provably exists and returns 32 records under its accession - so every provider's zero in that sweep is uninterpretable
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseanalyses/core-complex-interactome-gap/run.py - gene_of() regex on the MITAB alias field, PSICQUIC search/query/<accession>?format=tab25 endpoint; and the returned MITAB rows for query/Q03164 and query/Q9UHB7 showing interaction EBI-4321349 with alias field psi-mi:mll_aff4_fusion(display_short)|psi-mi:EBI-2620048(display_long); read and executed 2026-09-22· This repository / IntAct PSICQUIC (EMBL-EBI) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseIntAct PSICQUIC search/query/Q9UHB7 and /P48426 (format=tab25, maxResults=4000), all pubmed identifiers extracted per row, compared against IntAct REST findInteractions for the same accessions; run 2026-09-22· IntAct molecular interaction database (EMBL-EBI) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch record counts for 41 candidate interactor queries against KMT2A, MLL and MLL-fusion terms, run for interactome round 4· NCBI PubMed, queried 2026-09-19 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch comparison of alias-inflated and corrected queries for NELFE and EAF2, run for interactome round 4· NCBI PubMed, queried 2026-09-19 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch record counts for 42 candidate queries across FACT, NSL, MSL, the COMPASS remainder and Mediator, run for interactome round 5· NCBI PubMed, queried 2026-09-19 2026used by Interactome round 5: 42 queries, 13 entries written, 9 candidates rejected with counts, and four alias failures of four different kinds, Lineage-split dependency for the round 5 panel: 23 genes, 2 myeloid-identity artefacts caught, and 3 survivors of which one has no literature at all, NSL complex - the MOF assembly that five NUP98 fusions bind alongside MLL1, and that competes with MLL/COMPASS for WDR5
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q7Z3B3 (KANL1_HUMAN), KAT8 regulatory NSL complex subunit 1· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB search gene_exact:MED1 AND organism_id:9606 AND reviewed:true - returns Q15648 (MED1) and O95243 (MBD4, which lists MED1 as a synonym)· UniProt Knowledgebase, reviewed (Swiss-Prot), queried 2026-09-19 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryInterfant-21 International Collaborative Treatment Protocol for Infants Under One Year With KMT2A-rearranged Acute Lymphoblastic Leukemia or Mixed Phenotype Acute LeukemiaPrincess Maxima Center for Pediatric Oncology · ClinicalTrials.gov 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryA Phase 2 Study of Blinatumomab in Combination With Chemotherapy for Infants With Newly Diagnosed Acute Lymphoblastic Leukemia With Randomization of KMT2A-Rearranged Patients to Addition of VenetoclaxNational Cancer Institute (NCI) · ClinicalTrials.gov 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetana-q147-irx1-fusion-occupancy-is-confined-to-kmt2a-aff1 and absence-q149-... (this graph)Iqbal Lab oncofusion knowledge graph, beat Q152 · this project 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetQ154 IRX1/IRX2 cross-instrument occupancy table (gene body, promoter by fragment midpoints, promoter by bigWig)Iqbal Lab oncofusion knowledge graph, beat Q154 · this project 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetq151 null for the q147 occupancy rule at promoter scale, over 19,404 refGene promoters x 27 samplesIqbal Lab oncofusion knowledge graph, beat Q151 · this project 2026used by IRX2 is not fusion-occupied at promoter scale in GSE252378: 0 of 27 samples, against a null of 2.73, The 2.03-fold over-representation of shared windows among fusion-occupied promoters is generic promoter activity, not a fusion preference - and if it is not, the rule is finding something different from what it claims, The occupancy rule this project has used since q145 calls a tenth of ALL promoters occupied, and no entry using it records that
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetq151 threshold sensitivity sweep and near-miss decomposition, GSE252378Iqbal Lab oncofusion knowledge graph, beat Q151 · this project 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseIRX2-DT IRX2 divergent transcript [Homo sapiens (human)], Gene ID 153571NCBI Gene · NCBI Gene 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUCSC Genome Browser hg38 refGene track, chr5:2,745,000-2,760,000UCSC Genome Browser, api.genome.ucsc.edu · UCSC Genome Browser 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q969H0, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026used by Is menin an SCF-FBXW7 substrate? A one-week immunoblot and a free desk scan that settle Arm A, MEN1-FBXW7 is four alleles of ONE BRET assay, all typed 'mutation with no effect' - declined, and it is the most insidious class, Three of menin's nine declined partners are E3 ligase substrate receptors - either menin turnover is ubiquitin-controlled, or substrate receptors are this beat's artefact signature
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch counts for KMT2A/MAML2/menin intersection queries, run 2026-09-19National Center for Biotechnology Information (NCBI), PubMed · PubMed (NCBI E-utilities) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUCSC Genome Browser REST API, hg38 ncbiRefSeqSelect track, NM_005934.4 (MLLT1) and NM_004529.4 (MLLT3)· UCSC Genome Browser 2026used by Is the YEATS asymmetry just intron geometry? Computed from hg38: the direction is explained, the magnitude is not, and both genes fail the same prediction, The 2x2 paralogue swap: separate 'is the reader there' from 'which backbone is it on', in one background with matched expression, The transfer rule: which MLL-AF9 results can be carried into t(11;19) and t(4;11), and which are statements about a protein missing a reading module, The YEATS asymmetry is breakage geography, not selection: the reader's fate is decided by where topoisomerase II cuts, before any leukaemia exists
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P13612 (ITA4_HUMAN)· UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseChEMBL molecule record CHEMBL3989958 (IVOSIDENIB)ChEMBL, EMBL-EBI · ChEMBL database 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42431943Distinct roles of the JADE and BRPF scaffolding subunits of the acetyltransferase HBO1 complex.Gaurav N, Ebert LK, Lachance C, Selvam K, Chen RW, et al. · Nat Commun 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human entry P23458 (JAK1_HUMAN)UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P23458 (JAK1_HUMAN), SUBCELLULAR LOCATION comment with its evidence array read back field by field, fetched live 2026-09-21UniProt Consortium · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q86VZ6 (JAZF1_HUMAN): reviewed record, length, gene names and subcellular-location commentUniProt Consortium · UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC record for JAZF1 (HGNC:28917)HUGO Gene Nomenclature Committee · HGNC REST 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q15652 (JHD2C_HUMAN, 2,540 aa) FUNCTION and SUBUNIT comments; resolved by gene_exact:JMJD1C and gene_exact:KDM3C both returning the same single reviewed human row, with the primary gene name and length read back· UniProt Consortium 2026used by JDI-12 - published as a JMJD1C inhibitor that preferentially kills KMT2A-rearranged leukaemia and spares cord blood, then used as 'KDM3i' to CREATE KMT2A rearrangements in cord-blood progenitors, by two papers that do not cite each other, JMJD1C / KDM3C - named in three entries of this graph as one of the only loci that loses fusion occupancy under a menin inhibitor, ranked 23rd of 17,728 for KMT2A-selective dependency in this project's own scan, with the strongest published shRNA effect in SEM - and no entry until now
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryClinicalTrials.gov registry records for NCT05453903, NCT06852222, NCT03013998 and NCT07223814, retrieved via the ClinicalTrials.gov API v2 intervention search on bleximenib / JNJ-75276617Janssen Research & Development, LLC; Beat AML, LLC; Stichting Hemato-Oncologie voor Volwassenen Nederland (HOVON) · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryA Phase I/Ib Study of JNJ-75276617 in Combination With Conventional Chemotherapy for Pediatric and Young Adult Participants With Relapsed/Refractory Acute Leukemias Harboring KMT2A, NPM1, or Nucleoporin Gene AlterationsJanssen Research & Development, LLC · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P17535 (JUND_HUMAN), Transcription factor JunDUniProt Consortium · UniProtKB/Swiss-Prot 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for the NSL complex subunits against KMT2A, MLL and leukaemia, run for interactome round 5· NCBI PubMed, queried 2026-09-19 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41680331Integrative transcriptomics and electrophysiological profiling of hiPSC-derived neurons identifies novel druggable pathways in Koolen-de Vries Syndrome.Verboven AHA, Puvogel S, Latour BL, Kolsters N, Lewerissa EI, Mijdam R, Dyke E, Duineveld D, Zoodsma M, Claassen WJJ, Oudakker A, Schoenmaker C, Koolen DA, de Vries BBA, 't Hoen PAC, Linda K, Nadif Kasri N · Mol Psychiatry 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for the NSL complex subunits against KMT2A, MLL and leukaemia, run for interactome round 5· NCBI PubMed, queried 2026-09-19 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9H9L4 (KANL2_HUMAN), KAT8 regulatory NSL complex subunit 2· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q92830 (KAT2A_HUMAN), Histone acetyltransferase KAT2AUniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q92831 (KAT2B_HUMAN), Histone acetyltransferase KAT2BUniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q92831 (KAT2B_HUMAN) - SUBCELLULAR LOCATION comment block with evidence codes· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q92993 (KAT5_HUMAN), Histone acetyltransferase KAT5UniProt Consortium · UniProtKB, retrieved 2026-09-20 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42575441ATR-dependent phosphorylation of the histone acetyltransferase HBO1 suppresses chromatin binding and promotes replication stress responses.Zong C, Zhang J, Zhang Z, Cai Y, Wang Y, Fang Y, Zheng G, Li Q, Wang L, Shen J · J Biol Chem 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9H7Z6 (KAT8_HUMAN) - subcellular location with evidence codes, fetched 2026-09-20UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42560720Whack-a-menin: zifto's preclinical activity and mutant MEN1Bernt KM · Blood 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O60341 (KDM1A_HUMAN), Lysine-specific histone demethylase 1A· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record count for (MLL OR KMT2A) AND (KDM1A OR LSD1 OR AOF2 OR BHC110), run for this beat· NCBI PubMed, queried 2026-09-19 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9Y2K7 (KDM2A_HUMAN), Lysine-specific demethylase 2A / CXXC-type zinc finger protein 8 / FBXL11UniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.dataset
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetNCBI GEO GSE260742 locus table over UCSC mm10 refGene windows, analyses/q117-gained-fusion-occupancy/locus-table.json· NCBI Gene Expression Omnibus 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O94953 (KDM4B_HUMAN), Lysine-specific demethylase 4BUniProt Consortium · UniProt 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus entry CVCL_0095 (SEM)Bairoch A; SIB Swiss Institute of Bioinformatics · Cellosaurus 2026used by KDM4C (JMJD2C/GASC1) — recruited by the retained KMT2A N-terminus, drugged in a KMT2A::AFF1 line, and invisible to CRISPR, One experiment that decides whether KDM4C is a target or the KDM4 family is: paralogue rescue of SD70 sensitivity in SEM, SEM (CVCL_0095) — the workhorse, from a five-year-old, and microsatellite unstable
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasegnomAD v4 loss-of-function constraint for KDM4C (ENSG00000107077) via the gnomAD GraphQL APIGenome Aggregation Database, Broad Institute · gnomAD 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9H3R0 (KDM4C_HUMAN), lysine-specific demethylase 4CUniProt Consortium · UniProt 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P29375 (KDM5A_HUMAN) - Lysine-specific demethylase 5A, Homo sapiensUniProt Consortium · UniProt Knowledgebase 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseENCODE Portal experiment search, type=Experiment, assay_title=TF ChIP-seq, status=released, target.label=KDM5AENCODE Project Consortium · ENCODE Portal 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI E-utilities esearch over PubMed, db=pubmed, querytranslation read back for every queryNational Center for Biotechnology Information · NCBI Entrez Programming Utilities 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed searches for KDM6A/UTX in MLL1 and KMT2A-fusion complexes, conducted for this graph on 2026-09-18; no primary study retrievedOncofusion Knowledge Graph project, using the NCBI PubMed E-utilities · Literature search 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human record O15054 (KDM6B) - gene_primary, protein name and length, fetched 2026-09-20UniProt Consortium; query run by this project · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q07666 (KHDR1_HUMAN), human KHDRBS1, 443 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q5VWX1 (KHDR2_HUMAN), human KHDRBS2, 349 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O75525 (KHDR3_HUMAN), human KHDRBS3, 346 aa· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 42349662Mixed phenotype acute leukemia: Lineage assignment, immunophenotypic classification and genetic insights.Leventaki V, Wang SA · Hum Pathol 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P10721 (KIT_HUMAN), Mast/stem cell growth factor receptor Kit, SCFR, EC 2.7.10.1, CD antigen CD117, 976 aa, single reviewed human record, primary gene name KIT· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P21583 (SCF_HUMAN) - Kit ligand· UniProtKB 2026used by KITLG (stem cell factor) - the niche ligand of KIT, zero mentions anywhere in this graph, and its own symbol collides with the SCF ubiquitin ligase this corpus talks about constantly, Niche proteins enumerated and NOT written in this tranche, and four symbol traps measured while doing it - three of them new to the registry
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseDepMap CRISPR (Chronos) gene effect and gnomAD constraint, retrieved via the Open Targets Platform GraphQL API and the gnomAD GraphQL APIBroad Institute DepMap; gnomAD; Open Targets · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databasePDBe SIFTS best_structures mapping for UniProt Q03164· EMBL-EBI PDBe API 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseHuman Protein Atlas - KMT2A (ENSG00000118058), machine-readable gene recordHuman Protein Atlas consortium · proteinatlas.org 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetPRIDE Archive PXD006201 - Characterisation of protein ubiquitination using UbiSite technology· PRIDE Archive, EMBL-EBI 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseIntAct molecular interaction database, REST findInteractions on Q03164 (KMT2A), 376 records retrieved 2026-09-23 by Q129· IntAct (EMBL-EBI) 2026used by KMT2A-ABT1 is one spoke-expanded BioPlex 3.0 AP-MS row in HEK293T in which ABT1 is the bait and KMT2A the prey, and ABT1's nucleolus is ECO:0000250 only - declined, KMT2A-ANOS1 is one spoke-expanded BioPlex 3.0 AP-MS row with ANOS1 - a secreted, cell-membrane axon-guidance protein - as the bait and KMT2A as the prey in HEK293T - declined, KMT2A-FGFBP1 is spoke-expanded BioPlex 3.0 AP-MS recovered in BOTH HEK293T and HCT116 - it passes BioPlex's own replication criterion and the partner is a secreted extracellular protein - declined, KMT2A-KRR1 is one spoke-expanded BioPlex 3.0 AP-MS row in HEK293T with KRR1 as bait and KMT2A as prey, sitting in a seven-member ribosomal block at the floor score - declined, KMT2A-OASL is one spoke-expanded BioPlex 3.0 AP-MS row with OASL as bait and KMT2A as prey; OASL is the only partner in the beat natively expressed in blood leukocytes, and its nucleolar annotation is uncoded - declined, with the compartment argument unavailable, KMT2A-PRKRA is one spoke-expanded BioPlex 3.0 AP-MS row with PRKRA (PACT) as bait and KMT2A as prey; PRKRA's only UniProt compartments are cytoplasm and perinuclear region, both uncoded - declined, KMT2A-TMCO1 is a single DSSO crosslink in one detergent fraction of isolated U2OS nuclei with no bait on either side; TMCO1 is an ER-membrane calcium channel and the source paper attributes 4% of its links to nucleus-ER contamination - declined, The ABT1/KRR1/UTP3 nucleolar triple: pre-registered, then adjudicated - it is not three proteins on two baits but a seven-member ribosomal block in one screen plus one hit in a neighbourhood that shows no nucleolar enrichment, and two of the four pre-registered discriminators were void exactly as the pre-registration predicted, The missing reagent: a KMT2A-fusion or wild-type-KMT2A proximity bait in a KMT2A-rearranged leukaemia line - IntAct has curated no KMT2A-bait interaction experiment since April 2015 and no PSIP1-bait since October 2012, The REST-wide direction audit Q104 asked for: scaffold-as-bait rows DO exist in the 36% of the record PSICQUIC hides - KMT2A is a bait in 96 of 376 rows across 18 publications and PSIP1 in 11 of 114 across 4, but the most recent is 2015 and 2012, and none of the thirteen never-discussed partners comes from one
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9ULW3 (ABT1): primary gene name, sequence length, subcellular location and function, retrieved 2026-09-23· UniProt Consortium 2026used by KMT2A-ABT1 is one spoke-expanded BioPlex 3.0 AP-MS row in HEK293T in which ABT1 is the bait and KMT2A the prey, and ABT1's nucleolus is ECO:0000250 only - declined, The ABT1/KRR1/UTP3 nucleolar triple: pre-registered, then adjudicated - it is not three proteins on two baits but a seven-member ribosomal block in one screen plus one hit in a neighbourhood that shows no nucleolar enrichment, and two of the four pre-registered discriminators were void exactly as the pre-registration predicted
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P23352 (ANOS1): primary gene name, sequence length, subcellular location and function, retrieved 2026-09-23· UniProt Consortium 2026used by KMT2A-ANOS1 is one spoke-expanded BioPlex 3.0 AP-MS row with ANOS1 - a secreted, cell-membrane axon-guidance protein - as the bait and KMT2A as the prey in HEK293T - declined, KMT2A-KRR1 is one spoke-expanded BioPlex 3.0 AP-MS row in HEK293T with KRR1 as bait and KMT2A as prey, sitting in a seven-member ribosomal block at the floor score - declined
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry O15516 (CLOCK_HUMAN), subcellular location and tissue specificity, retrieved 2026-09-24· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.dataset
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P82970, subcellular location, length and tissue specificity, retrieved 2026-09-24· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q53GT1, subcellular location, length and tissue specificity, retrieved 2026-09-24· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseNCBI GEO DataSets search, 2026-09-24NCBI Gene Expression Omnibus · NCBI GEO 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCancer Stat Facts: Leukemia - Acute Myeloid Leukemia (AML)National Cancer Institute Surveillance, Epidemiology, and End Results Program · SEER 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCancer Stat Facts: Leukemia - Acute Lymphocytic Leukemia (ALL)National Cancer Institute Surveillance, Epidemiology, and End Results Program · SEER 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41126738Age-specific mutation profiles and their prognostic implications in pediatric KMT2A-rearranged acute myeloid leukemiaShoji K, et al. · Haematologica 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for DSIF and NELF subunits and aliases against KMT2A and MLL, run for this beat· NCBI PubMed, queried 2026-09-19 2026used by KMT2A-rearranged cells need the factors retained through elongation MORE and the factors ejected at pause release LESS — a six-gene asymmetry nobody has reported, NELF — the brake that has to come off for elongation, absent from the KMT2A literature, and less required in KMT2A-rearranged lines than in any other leukaemia
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseIntAct molecular interaction database, REST findInteractions free-text query on 30021884, all 4,856 rows paginated and role-counted 2026-09-23 by Q129· IntAct (EMBL-EBI) 2026used by KMT2A-TMCO1 is a single DSSO crosslink in one detergent fraction of isolated U2OS nuclei with no bait on either side; TMCO1 is an ER-membrane calcium channel and the source paper attributes 4% of its links to nucleus-ER contamination - declined, PSIP1-GDF5 is a single DSSO crosslink in isolated U2OS nuclei with no bait on either side; GDF5 is a secreted cartilage growth factor, and the source paper itself attributes 30% of its cross-compartment links to contamination during nuclei isolation - declined
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41681872Impact of Fusion Partners and Transplantation Benefit in Intensively Treated KMT2A-Rearranged Acute Myeloid Leukemia.Shen H, Chen J, et al. · Cancers (Basel) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P42566 (EPS15_HUMAN) Epidermal growth factor receptor substrate 15, Homo sapiens, 896 aaUniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI E-utilities esearch over PubMed, query (MLL[Title/Abstract] OR KMT2A[Title/Abstract]) AND (gephyrin[Title/Abstract] OR GPHN[Title/Abstract]), run 2026-09-19, 3 records, all three titles readUS National Library of Medicine, PubMed · PubMed (E-utilities) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q8IZL2 (MAML2_HUMAN) and InterPro Pfam domain boundaries for MAML2UniProt Consortium; InterPro (EMBL-EBI) · UniProtKB / InterPro 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paperPMID 41834483Secondary T-Lymphoblastic Lymphoma With KMT2A::MAML2 Rearrangement Following Myeloid Sarcoma and RUNX1::RUNX1T1-Positive Acute Myeloid Leukemia.Li T, Wang A, Wu P, Sun H, Zhang L, Chen M, Zhao X, Wang H · Pediatric Blood & Cancer 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseNCBI E-utilities esearch over PubMed, query (MLL[Title/Abstract] OR KMT2A[Title/Abstract]) AND MYO1F[Title/Abstract], run 2026-09-19, 2 records, both titles readUS National Library of Medicine, PubMed · PubMed (E-utilities) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9NVA2 (SEP11_HUMAN) Septin-11, Homo sapiens, 429 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q15019 (SEPT2_HUMAN) Septin-2 / NEDD5, Homo sapiens, 361 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q99719 (SEPT5_HUMAN) Septin-5 / CDCrel-1, Homo sapiens, 369 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q14141 (SEPT6_HUMAN) Septin-6, Homo sapiens, 434 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UHD8 (SEPT9_HUMAN) Septin-9 / MLL septin-like fusion protein MSF-A, Homo sapiens, 586 aaUniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch counts for KMT2A/USP2/menin intersection queries, run 2026-09-19National Center for Biotechnology Information (NCBI), PubMed · PubMed (NCBI E-utilities) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P40818 (UBP8_HUMAN), Ubiquitin carboxyl-terminal hydrolase 8, with domain boundariesUniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetused by KMT2A's proximity promiscuity is BAIT-CLASS-SPECIFIC: it is recovered at twice its size-and-abundance prediction by RNA-binding-protein baits in a leukaemia cell and at exactly its prediction by transcription-factor baits in a kidney cell, Prey recovery in the two BioID depositions tracks SIZE and not abundance - and the interactome tail was being scored on the wrong side of the pair, because every one of the 22 partners is the BAIT and every core protein is the PREY
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human records Q9UMN6 (KMT2B), O14686 (KMT2D), Q8NEZ4 (KMT2C), Q8IZD2 (KMT2E), Q03164 (KMT2A), O15047 (SETD1A), Q9UPS6 (SETD1B) - gene_primary, length and canonical sequence, fetched 2026-09-20UniProt Consortium; queries and alignment by this project · Database 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41032751Fetal context conveys heritable protection against MLL-rearranged AML that depends on MLL3.Mendoza-Castrejon J, Yang W, Denby E, et al. · Blood 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human record Q8NEZ4 (KMT2C) - gene_primary, length and canonical sequence, fetched 2026-09-20UniProt Consortium; query run by this project · Database 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB Q8NEZ4 (KMT2C_HUMAN) SUBCELLULAR LOCATION comment, fetched 2026-09-21· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human records O14686 (KMT2D) and Q9UMN6 (KMT2B) - gene_primary, gene synonyms, protein names and length, fetched 2026-09-20UniProt Consortium; queries run by this project · Database 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB O14686 (KMT2D_HUMAN) SUBCELLULAR LOCATION comment, fetched 2026-09-21· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42409830
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB reviewed human record Q8IZD2 (KMT2E) - gene_primary, protein name and length, fetched 2026-09-20UniProt Consortium; query run by this project · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus record CVCL_7972 (KOPB-26)· Cellosaurus (SIB) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus cell line KOPN-8 (CVCL_1866)Bairoch A, et al.; Cellosaurus · Cellosaurus (SIB) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 41849234Discovery and preclinical activity of the menin-KMT2A inhibitor ziftomenib in acute leukemia models.Miao H, Wu T, Purohit T, Chen D, et al. · Blood 2026used by KOPN-8 (CVCL_1866): the field's default KMT2A::MLLT1 line, and its fusion protein has no YEATS domain, Menin dependence of KMT2A::MLLT1: real, repeatedly demonstrated, and always as one lane of a partner panel, Revumenib (SNDX-5613, Revuforj) — first approved menin–KMT2A interface inhibitor, Ziftomenib (KO-539, Komzifti) — once-daily menin inhibitor approved in NPM1-mutant AML
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 41711432Menin inhibitors display differential in vitro sensitivity in KMT2A-rearranged infant acute lymphoblastic leukemia.Dymock SCC, Oommen J, Malinge S, Cheung LC, Kotecha RS · Leuk Lymphoma 2026used by Kotecha group, Perth: the infant KMT2A-rearranged laboratory this graph had cited once, Papers we know exist, know matter, and cannot read, The state under menin inhibition — differentiation in AML, rapid death in ALL, and a GMP-like exit in the cells that switch lineage instead, Treating the five menin inhibitors as one drug, when a 2026 title says they are not
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42085603Combining menin and MEK inhibition to target poor prognosis KMT2A-rearranged RAS pathway-mutant acute myeloid leukemia.Scheidegger N, Schneider C, Alexe G, et al. · Blood Advances 2026used by KRAS - the commonest co-mutation in a disease that has almost none, and it is usually in a minority of the cells, No second driver means no second target - the quiet genome forecloses the combination logic that works in every other leukaemia, Track the sub-1% cooperating-lesion clones through menin inhibition, because nobody has measured what the drug selects for, Treating a subclonal lesion is selection pressure applied to the clone you did not aim at
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.newsKura Oncology pipeline page (ziftomenib programme and Kyowa Kirin collaboration)Kura Oncology, Inc. · kuraoncology.com 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseused by LAMP5 (BAD-LAMP) - a direct MLL-fusion target gene, a proposed immunotherapy antigen, and a brain protein, LAMP5 was proposed as an immunotherapy target for MLL-rearranged leukaemia without a normal-tissue filter; two atlases independently put it above 290 in the basal ganglia, and it is not partner-specific either, LAMP5-directed therapy for KMT2A-rearranged leukaemia would meet the basal ganglia, in a disease treated in infants and routinely treated into the CNS
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseused by LAMP5 (BAD-LAMP) - a direct MLL-fusion target gene, a proposed immunotherapy antigen, and a brain protein, LAMP5 was proposed as an immunotherapy target for MLL-rearranged leukaemia without a normal-tissue filter; two atlases independently put it above 290 in the basal ganglia, and it is not partner-specific either
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q86U70 (LDB1_HUMAN), LIM domain-binding protein 1, feature table and sequenceUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseEnsembl REST API lookup, LDB1 (ENSG00000198728), canonical transcript ENST00000673968 with exon and translation coordinatesEnsembl (EMBL-EBI) · Ensembl REST 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UJU2 (LEF1_HUMAN), Lymphoid enhancer-binding factor 1 — accession, primary gene name, length and subcellular-location comment retrieved 2026-09-24· UniProt Consortium, EMBL-EBI/SIB/PIR 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed search for LEO1 in the context of KMT2A/MLL-fusion leukemia, conducted for this graph on 2026-09-18; no primary subunit-level study retrievedOncofusion Knowledge Graph project, using the NCBI PubMed E-utilities · Literature search 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB Q8WVC0 (LEO1_HUMAN) feature table and PDB cross-references; RCSB entries 6TED, 7OPC and 8A3Y verified via the RCSB data APIUniProt Consortium; RCSB Protein Data Bank · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseused by let-7 microRNA family (12 HGNC loci) - the effector LIN28B blocks. CORRECTED IN-SESSION: the headline 'zero papers in KMT2A leukaemia' was a NAME-LIST ARTEFACT; searching MLL instead of KMT2A returns three, one of them directly on point, PROPOSED: measure let-7 and restore it in the human fetal-liver KMT2A::AFF1 model - an axis measured in mouse MLL-fusion AML but never in the index fusion
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseused by LIN28B - a one-row BioID prey of KMT2A that a 2026 Blood paper shows is REQUIRED for KMT2A::AFF1 to transform human fetal cells, LIN28B localization - a nucleolar pool that sequesters pri-let-7, a predominantly cytoplasmic steady state with cell-cycle-dependent nuclear entry, and NO measurement in any haematopoietic cell
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.reviewPMID 42362807Plasticity under pressure: biology and detection of lineage switch in acute leukemia.Kovach AE, ..., Davis KL · Leukemia 2026used by Lineage drift - the partial state between B-ALL and AML, and the fact that nobody has published the ORDER in which markers change, Lineage switch as antigen escape from CD19-directed therapy in KMT2A-rearranged leukemia, Which marker moves first? A re-analysis of flow files that already exist, to put an order on lineage switch
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.databaseUniProtKB P29375 (KDM5A_HUMAN): FT REGION 1623..1690 /note='Interaction with LMO2' /evidence='ECO:0000269|PubMed:9129143'; SQ 1690 AAUniProt Consortium; flat file fetched by this project 2026-09-20 · Database record 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysisKMT2A 14-3-3 motif scan: does the retained fragment carry a phosphorylation-gated handle?· Oncofusion knowledge graph (internal analysis) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseused by Low-grade endometrial stromal sarcoma is a family of NuA4-acetyltransferase-to-Polycomb fusions, and that is why one of MBTD1's two fusions looks nothing like the other, ZMYND11::MBTD1 AML is menin-inhibitor sensitive despite having no KMT2A rearrangement, because the translocation deletes ZMYND11's MYND domain and with it a physical brake on wild-type KMT2A, ZMYND11::MBTD1 is the KMT2A-fusion architecture assembled from different parts - and the part it throws away is a direct physical brake on KMT2A itself
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUniProtKB - Q9NX58 (LYAR_HUMAN), Cell growth-regulating nucleolar protein· UniProt Knowledgebase 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseNCBI PubMed esearch, bounded-absence query (counted negative)· NCBI E-utilities 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCell Ontology term CL:0000936 early lymphoid progenitor, retrieved via the EMBL-EBI Ontology Lookup Service OLS4 APIEMBL-EBI Ontology Lookup Service; Cell Ontology consortium · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q8IZL2 (MAML2_HUMAN), Mastermind-like protein 2, with InterPro/Pfam domain boundariesUniProt Consortium; InterPro (EMBL-EBI) · UniProtKB / InterPro 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch counts for MAML2 symbol, alias and partner queries, run 2026-09-19National Center for Biotechnology Information (NCBI), PubMed · PubMed (NCBI E-utilities) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed E-utilities esearch, db=pubmed, run 2026-09-20NCBI · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q99558 (M3K14_HUMAN), Mitogen-activated protein kinase kinase kinase 14UniProt Consortium · UniProt 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q99558 (M3K14_HUMAN) SUBCELLULAR LOCATION and TISSUE SPECIFICITY comments, fetched 2026-09-21UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O95819 (M4K4_HUMAN) gene synonyms, SUBCELLULAR LOCATION and length, fetched 2026-09-21UniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q13164 (MK07_HUMAN), human MAPK7, 816 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P31153 (METK2_HUMAN), S-adenosylmethionine synthase isoform type-2UniProt Consortium · UniProt 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetAge-restricted vulnerability panel: PLK1, AURKA, MAT2A and FFAR2 dependency in KMT2A-rearranged leukaemia linesOncofusion knowledge graph internal analysis · Oncofusion knowledge graph (internal analysis, ana-age-restricted-vulnerability-panel) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9UIS9 (MBD1_HUMAN), Methyl-CpG-binding domain protein 1 / CXXC-type zinc finger protein 3UniProt Consortium · UniProtKB 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42322117Aberrant splicing of MBD1 reshapes the epigenome to drive convergent myeloerythroid defects in MDS.Chen HTT, Joshi P, et al. · Blood 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.databaseDepMap KMT2A-selective dependency scan over 17,728 genes: analyses/depmap-kmt2a-selective-scan-full/results.json, generated 2026-09-19.· DepMap via this repository 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q05BQ5 (MBTD1_HUMAN); HGNC:19866 (mbt domain containing 1); Ensembl ENSG00000011258· UniProt / HGNC / Ensembl 2026used by MBTD1 - the H4K20me1/me2 reader inside NuA4/TIP60, the quiescence brake on adult haematopoietic stem cells, and the 3' partner of ZMYND11::MBTD1 whose methyl-lysine cage the fusion carries and does not use, MBTD1 is the effector-recruiting half of a leukaemia fusion and the addressing half of a sarcoma fusion while donating nearly all of itself to both - so the junction, not the parts, assigns the role, MBTD1::EZHIP (MBTD1-CXorf67), t(X;17)(p11.2;q21.33) - MBTD1's other fusion, in which a NuA4 subunit delivers an H3K27M-mimicking PRC2 poison to low-grade endometrial stromal sarcoma, ZMYND11::MBTD1, t(10;17)(p15;q21) - a chromatin reader welded to the NuA4/TIP60 acetyltransferase, maintaining Hoxa/Meis1/Myb/Myc/Sox4 in AML: the KMT2A-fusion architecture built from different parts
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseused by MBTD1 is the effector-recruiting half of a leukaemia fusion and the addressing half of a sarcoma fusion while donating nearly all of itself to both - so the junction, not the parts, assigns the role, MBTD1::EZHIP (MBTD1-CXorf67), t(X;17)(p11.2;q21.33) - MBTD1's other fusion, in which a NuA4 subunit delivers an H3K27M-mimicking PRC2 poison to low-grade endometrial stromal sarcoma
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC:33738 (EZHIP, 'EZH inhibitory protein') and UniProtKB Q86X51 (EZHIP_HUMAN)· HGNC / UniProt 2026used by MBTD1::EZHIP (MBTD1-CXorf67), t(X;17)(p11.2;q21.33) - MBTD1's other fusion, in which a NuA4 subunit delivers an H3K27M-mimicking PRC2 poison to low-grade endometrial stromal sarcoma, The coverage checker the standing brief mandates overwrites its own HGNC index mid-loop, so every symbol after the first no-match is answered wrongly - and the wrong answer is 'treat any answer as unsafe'
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42237892The myeloid cell leukaemia-1 inhibitor MIK665 is a potent therapy in preclinical models of paediatric acute myeloid leukaemia.Connerty P, Colgan JN, El-Najjar F, ..., Lock RB · Br J Haematol 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42120360MCL1 inhibition to enhance the efficacy of MYB targeting in pediatric acute myeloid leukemia.Tsakaneli A, Che N, Virely C, ..., Williams O · Cell Death Dis 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q07820 (MCL1_HUMAN), Induced myeloid leukemia cell differentiation protein Mcl-1UniProt Consortium · UniProt 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9HAF1 (EAF6_HUMAN): reviewed record, length, gene names and subcellular-location commentsUniProt Consortium · UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC record for MEAF6 (HGNC:25674)HUGO Gene Nomenclature Committee · HGNC REST 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB canonical sequences Q03164 (KMT2A, 3969 aa) and Q9UMN6 (KMT2B, 2715 aa), fetched 2026-09-20UniProt Consortium; sequences fetched and aligned by this project · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysisanalyses/the-eviction-clause-was-reachable-all-along/run.py and results.json plus the input extension, this repository; bins from C:/Temp/q117, C:/Temp/q124 and C:/Temp/q125, computed 2026-09-23 with zero downloads; FLAG series is GSM8123407-412, mislabelled in GEO as H2AK119ub rep1Oncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026used by Measured against a technical floor of 4-10% from two independent input pairs, PCGF1 loss lowers baseline fusion occupancy at the top-FLAG sites by 16.3% and changes the DOT1L inhibitor's effect on that occupancy by 22.8% - while leaving the menin inhibitor's effect unchanged at 1.3%. In the knockout SGC0946 displaces more fusion than VTP-50469 does, which is the opposite of the control, PCGF1 loss flattens the fusion's genomic distribution - the knockout-over-control share ratio rises monotonically from 0.810 at the highest-signal decile to 1.136 at the lowest while both input pairs stay flat - and the drug does something spatially different: VTP-50469 evicts almost only at the top 0.1% (0.7554 against 0.9937 at the decile below). The drug acts at the peaks, the genotype acts in the bulk, Salvaged from a session-limit death: the DMSO-versus-DMSO selection control cannot be run cleanly on GSE260742, because every same-condition vehicle pair is confounded - two differ about three-fold in aggregate signal and the only admissible same-mark pair crosses processing states (filt.bam.tdf versus tdf). Its automated verdict of MANUFACTURED is NOT supported, and the control remains UNRUN rather than passed or failed, Six files titled H2AK119ub rep1 are FLAG ChIPs, so prediction 5's eviction clause - declared UNREACHABLE by Q124 - was computable from bins already on disk. It is now scored and it CONFIRMS: VTP-50469 removes the same share of fusion occupancy in the PCGF1 knockout as in the control, 0.7655 against 0.7554, a 1.3% difference against 22.8% genotype variation on a control drug, The first measurement of any histone mark outside the top 0.1% of fusion sites: by ratio the drug's mark response is confined to the peaks as pre-registered, while in ABSOLUTE share the movement at the decile below is 5 to 33 times larger - though that is partly guaranteed by the stratum being 100x bigger. H3K79me2 falls at the peaks (0.8065) and is not measurably changed at D1, and H3K4me3 and H3K79me2 both break the floor at the lowest decile, Three unnamed things at once: the DOT1L-PRC1.1 deposition names the fusion, the cell types and both inhibitors with concentrations
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisanalyses/is-any-pi-axis-actually-thin/run.py and results.json, this repository, computed 2026-09-23 over the committed node files; motivated by the Q137 analogy beat's correction of the cycle-113 beat selectionOncofusion knowledge graph, coordinator · internal analysis, reproducible from the repository 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for the Mediator subunits MED1, MED12, MED14, MED23 and MED24 against KMT2A, MLL and leukaemia, run for interactome round 5· NCBI PubMed, queried 2026-09-19 2026used by MED12 - a named menin-associated protein that restrains menin's transcriptional output, and the anchor of the CDK8 module a KMT2A-r AML paper co-targets, MED23 — rank 16 of 17,728, survives the lineage split with the B-lineage half stronger, and is not absent from the leukaemia literature after all
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q93074 (MED12_HUMAN), Mediator of RNA polymerase II transcription subunit 12· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseIntAct REST findInteractions: interactor EBI-2620048, interaction EBI-4321349 / IMEx IM-16559-13, experimentalRoleA=bait, hostOrganism=Homo sapiens HeLa, retrieved 2026-09-22· IntAct molecular interaction database (EMBL-EBI) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB A0JLT2 (MED19_HUMAN): features, comments and evidence codes; HGNC:29600 via rest.genenames.org; Ensembl ENSG00000156603 coordinates; retrieved 2026-09-22· UniProt Consortium / HGNC / Ensembl 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetanalyses/depmap-kmt2a-selective-scan-full/results.json - 17,728 protein-coding genes, 11 Cellosaurus-annotated KMT2A-rearranged versus 43 other leukaemia lines, computed 2026-09-19· DepMap (Broad Institute), via this repository's scan 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetanalyses/mediator-module-split/result.json - membership from EBI Complex Portal human table CPX-3227 / CPX-3232 / CPX-3263· This repository / EBI Complex Portal 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9ULK4 (MED23_HUMAN), Mediator of RNA polymerase II transcription subunit 23· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q9ULK4 (MED23)· UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseChEMBL database version 34: target_search for MED26 / Mediator complex subunit 26 returned no target entity; comparator targets CHEMBL3232684, CHEMBL3132741, CHEMBL4295801 and CHEMBL4295761 queried by target_search and get_bioactivityEMBL-EBI ChEMBL · ChEMBL 2026used by MED26 — a common-essential Mediator subunit with a solved 87-residue domain and no ChEMBL target entity at all, VTP-50469 - the preclinical menin-KMT2A interface inhibitor that almost every chromatin experiment in this field actually used, and which had no entry of its own in this graph, ZFP64 — rank 4 on selectivity, and there is not even a ChEMBL entry for it
- speculative confidence 1 of 5: Our own inference or analogy. Not shown to be true.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O95402 (MED26_HUMAN) - SUBCELLULAR LOCATION comment block with evidence codes· UniProt Consortium 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisCore Mediator against its CDK8 kinase module, subunit by subunit, with pan-essentiality and expression controls· Oncofusion knowledge graph (internal analysis) 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysisExpression control for the paralogue splits and the ALAS1/ALAS2 comparison, against Human Protein Atlas cell-line RNA· Oncofusion knowledge graph (internal analysis) 2026used by Mediator's KMT2A signal is in its pan-essential core, CDK8 is expressed and not required at all, and MED13L is rank 9 while its paralogue MED13 is rank 13,569, The paralogue split survives the expression control and the ALAS2 control does not: ING4 is transcribed MORE than ING5 and is not required at all
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseRCSB PDB structure search against UniProt accession Q06413 (zero results) and UniProtKB Q06413 cross-references, both retrieved via their REST APIsRCSB Protein Data Bank; UniProt Consortium · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q06413 (MEF2C_HUMAN) and InterPro/Pfam domain assignments, retrieved via the UniProt and InterPro REST APIsUniProt Consortium; InterPro · Databases 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O00470 (MEIS1_HUMAN), retrieved via the UniProt REST APIUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseRCSB PDB entries 4XRS and 5EGO, verified against the RCSB data API for title, experimental method and resolutionRCSB Protein Data Bank · RCSB PDB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O00470 (MEIS1_HUMAN) - subcellular location with evidence codes, fetched 2026-09-20UniProt Consortium · UniProtKB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42441717Meis1 isoform diversity orchestrates neural progenitor differentiation by regulating ATOH1 degradation at distinct subcellular compartments.Owa T, Adachi T, Shiraishi R, Ichijo K, Ji K, Mizuno M, Suyama K, Nishitani K, Hasegawa I, Sone M, Kawauchi D, Nishioka T · PLoS Biol 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseREVUFORJ (revumenib) and KOMZIFTI (ziftomenib) US prescribing information, retrieved via the openFDA drug label APIUS Food and Drug Administration · openFDA 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry O00255 (MEN1_HUMAN), SUBCELLULAR LOCATION comment and feature tableUniProt Consortium · UniProtKB 2026used by MEN1 / menin — the adaptor the fusion cannot work without, Menin residue numbers: the resistance literature (G331R) and the crystal structures (residue 326) disagree by exactly five, Menin's two nuclear localisation signals, 479-497 and 588-608: mapped in 1998, verified residue-for-residue today, annotated by UniProt nowhere - NLS-1 in no structure at all, NLS-2 resolved in one, The menin-gamma-H2A.X motif, menin Val371-Gln400: necessary, sufficient as a peptide, and the nine residues at its centre have never been seen in any of the 69 menin structures, The residue-type numbering check passed a site that is in the wrong place, The ten reported menin-inhibitor escape substitutions are each one nucleotide change from the MEN1 sequence - which the sources could not have shown otherwise - so the useful outputs are a 25-variant validation panel and a burden threshold, not the headline, Three of menin's nine declined partners are E3 ligase substrate receptors - either menin turnover is ubiquitin-controlled, or substrate receptors are this beat's artefact signature, UniProt's menin 214-390 FANCD2 region is not a surface: it spans three spatial lobes and 29.9% of menin's solvent-accessible area, so its twenty-residue overlap with the gamma-H2A.X motif is what chance gives you
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42103719CRISPR base editor screening identifies spectrum of MEN1 mutations impacting menin inhibitors in clinical trialsBourgeois W, ..., Armstrong SA · Nature Communications 2026used by MEN1 drug-interface mutations — the first proof that a chromatin drug can drive Darwinian escape in patients, Model: resistance-mutation prediction - cannot be trained. There are six patient-observed labels in the world, and a base-editor screen already does the job better, Switching menin inhibitors: four substitutions defeat all of them, three defeat only some, and the map now exists, The ten reported menin-inhibitor escape substitutions are each one nucleotide change from the MEN1 sequence - which the sources could not have shown otherwise - so the useful outputs are a 25-variant validation panel and a burden threshold, not the headline
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P31749, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P15056, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q15762, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P00533, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q8N2W9, subcellular location, length and tissue specificity, retrieved 2026-09-24· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P60484, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q13485, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry O43791, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry Q86WB0, subcellular location and tissue specificity, retrieved 2026-09-23· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O00255 (MEN1_HUMAN) fetched live from rest.uniprot.org on 2026-09-24 by Q192; each of the fourteen positions indexed into the returned sequence string and the residue printed and compared against the published mutation nomenclature; 14 of 14 matched· UniProt Consortium / this repository 2026used by Menin binds RPA2 directly, the contact maps to RPA2 aa 43-171 across its low-affinity ssDNA site, and three MEN1 patient missense mutations abolish it - a 2003 finding that this graph had never cited despite menin being its central node, RPA2 (RPA32) - the middle subunit of replication protein A, whose disordered N-terminus is the phospho-switch of the replication-stress response and whose 43-171 region binds menin
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P15927 feature table (DNA binding, OB, residues 74-148), fetched live 2026-09-24; and Fan J, Pavletich NP, 'Structure and conformational change of a replication protein A heterotrimer bound to ssDNA', Genes Dev 2012;26(20):2337-47, PMID 23070815, DOI 10.1101/gad.194787.112· UniProt Consortium; Genes & Development 2026used by Menin binds RPA2 directly, the contact maps to RPA2 aa 43-171 across its low-affinity ssDNA site, and three MEN1 patient missense mutations abolish it - a 2003 finding that this graph had never cited despite menin being its central node, RPA2 (RPA32) - the middle subunit of replication protein A, whose disordered N-terminus is the phospho-switch of the replication-stress response and whose 43-171 region binds menin, RPA2 is the only compartment-compatible candidate of the six and the corpus already has a KMT2A resection thread it would fit — but it is an abundant ssDNA-binding subunit on 6 spectra in a benzonase-treated lysate with no RPA1 or RPA3 co-recovered — declined, thread flagged, Where RPA actually is: nucleoplasmic and diffuse until there is single-stranded DNA, then punctate prereplication foci at the G1/S border, damage-induced foci with RAD51, and a PML-body pool - and the subunits differ in how well any of this is measured
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.datasetOncofusion knowledge graph entry ana-reanalysis-of-ml2-mll1n-chip-for-gained-peaks-under-vtp-50469, evidence E3· Iqbal Lab oncofusion knowledge graph 2026used by Menin inhibition removes the fusion from its strongest sites without relocating it to a new programme, and PRC1.1 fills in only where the eviction is complete - so the drug's chromatin action is subtraction plus local substitution, not redistribution, The falsifier that decides the beat, run: 65.6% of the fusion's own top sites overlap a CpG island and 1 of the 52 sites it formally 'gains' under a menin inhibitor does - 1.35-fold over a class-matched null, Fisher p = 0.53 - so the gained set does not carry the signature of CXXC-driven binding and the redistribution model is refuted on its own predicted substrate
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseIntAct REST findInteractions/25962847 (Cheng et al. 2015), 12 records, figure-legend annotated, fetched 2026-09-21· EMBL-EBI IntAct 2026used by Menin is a corepressor of the LXR sterol sensors - one paper supplies three of this graph's twelve missing partners, and the function has never been written down here, NR1H2 / LXR-beta - the paralogue arm of the menin-LXR contact, present in both species and absent from the paper's conclusion, NR1H3 / LXR-alpha - the best-observed of the three MEN1 sterol partners, with both directions curated in two species, and menin as its corepressor, SREBF1 / SREBP-1 - the weakest of the three MEN1 sterol partners, because it is simultaneously the pathway's readout
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseIntAct REST record EBI-1801742 for the MEN1-PSIP1 pair, fetched 2026-09-21· EMBL-EBI IntAct 2026used by Menin is the best-observed of the six core proteins and the only one whose interval separates from the rest - the interface the programme is built on is the one the record actually supports, PSIP1-FOXK2: a single TAP row from the same TF atlas as the RBPJ decline - kept as a lead rather than declined, because FOXK2 is a chromatin-recruiting forkhead expressed in lymphoid cells and LEDGF is a chromatin-recruiting tether, PSIP1-RBPJ - DECLINED. A 214-purification transcription-factor TAP atlas that this beat's own atlas heuristic failed to flag, and the Notch connection is the reason to say so out loud, PSIP1-SDC1 - DECLINED as an interaction, kept for the splicing thread: nuclear syndecan-1 co-IP in a mesothelioma line recovers LEDGF among an RNA-splicing-enriched network, RBBP8 / CtIP - the only unwritten core-complex partner with a DIRECT-interaction record, and the graph already held its mechanism without holding the protein, What a curated interaction row actually claims: spoke expansion, and the ladder from 'was in the same tube' to 'touches'
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseanalyses/q36-menin-residue-axis/run.py - lobe assignment and ligand footprints on PDB 3U84, 7UJ4, 8VA6, 9WKU, 8IG0 and 4GQ6, run 2026-09-22· RCSB PDB, computed 2026used by Menin stimulates homology-directed repair through Chk1 and the region required is 1-228: a 2010 paper that is cited in no entry of this graph and in no reference list of the 2026 paper that reports the same conclusion, The menin-inhibitor class splits at Val371: three of four clinical compounds contact the first residue of the gamma-H2A.X motif and bleximenib does not, so DNA-repair effects should separate from KMT2A-displacement effects within the class
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.analysiszhou-group-function-scan: GO:BP enrichment of each menin/H2AK119ub group against Zhou's own called set as custom background, g:Profiler g:SCS corrected· Oncofusion knowledge graph (internal analysis) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysiszhou-group-function-scan results: bivalent group GO:BP terms and corrected p-values· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetanalyses/q34-menin-surface-geometry/run.py - menin surface geometry over all 69 O00255 PDB depositsQ34-menin-surface-map · Oncofusion Knowledge Graph 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetanalyses/q34-menin-surface-geometry/run.py - menin surface geometry over all 69 O00255 PDB depositsQ34-menin-surface-map · Oncofusion Knowledge Graph 2026used by Menin's nucleosome grip (8GPN): a three-patch surface at menin 353-362, 428-442 and 556-587 that holds H3, H4 and H2B - and touches H2A at exactly one residue, The SvID, menin 360-445: a truncation boundary the field reads as a domain, whose functional residues D418 and W436 are 10-20 A from every menin drug - but whose first ten residues ARE the drug pocket
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.computation_on_public_coordinatesObserved-residue survey of all 69 menin (UniProt O00255) PDB deposits, with a residue-identity guard against non-corresponding deposited numberingking, Oncofusion knowledge graph, cycle 64 · analyses/menin-nls-structural-coverage/run.py 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q9HCE5 (MET14_HUMAN), human METTL14, 456 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q86U44 (MTA70_HUMAN), human METTL3, 580 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC REST API record for MIR196B and Ensembl REST API gene lookups (MIR196B, HOXA9, HOXA10), assembly GRCh38HUGO Gene Nomenclature Committee; Ensembl / EMBL-EBI · HGNC / Ensembl 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseHGNC REST API records for MIR9-1, MIR9-2, MIR9-3 and Ensembl REST API gene lookups (MIR9-1/2/3, MEF2C), assembly GRCh38HUGO Gene Nomenclature Committee; Ensembl / EMBL-EBI · HGNC / Ensembl 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed database queries 'miR-9 AND MLL AND leukemia' (4 records) and 'miR-9 AND KMT2A AND rearranged AND leukemia' (0 records), executed 2026-09-18National Library of Medicine, PubMed · PubMed 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paperPMID 41692013Bortezomib and vorinostat in combination with mitoxantrone, dexamethasone, and pegasparaginase during induction and reinduction for infants with acute lymphoblastic leukaemia: a multicentre single-arm phase 1/2 study.Gruber TA, Jeha S, Deyell RJ, Lewis V, Chang BH, Lowe EJ, et al. · Lancet Haematol 2026used by Mitoxantrone - the Interfant-06 protocol says it is less cardiotoxic than daunorubicin, and the largest survivor cohort ever assembled says it is about seventeen times worse per milligram, Native E. coli asparaginase - the second-largest in-vitro resistance signal in infant ALL, and a different product from the pegylated one four doses later, Pegaspargase - the same enzyme wearing a polymer, dosed in units that are not the other product's units, and now dosed to a level in every group except infants, Romidepsin - the HDAC inhibitor with the best preclinical case in KMT2A-rearranged INFANT ALL specifically, and a mechanism that is not about histones at all, Vorinostat (SAHA) - the only HDAC inhibitor given to newly diagnosed infants with ALL, in a 50-patient trial whose endpoint was tolerability and which reported four treatment-related deaths, all infectious
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 41063702Acute leukemia of ambiguous lineage: the known and the uncertainSherban A, Wolach O · Haematologica 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P42568 (AF9_HUMAN), SUBCELLULAR LOCATION comment and feature tableUniProt Consortium · UniProtKB 2026used by MLLT3 / AF9 — a famous fusion partner that is not a dependency, and a hub domain that is, The KMT2A::MLLT3 chimeric protein: what survives the join on each side, in residue numbers - and the four AF9 modules that do not, Where KMT2A::MLLT3 sits in the nucleus: two papers, both overexpression, both from before 2005 - and the fusion carries no AF9 import signal
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P55198 (AF17_HUMAN) Protein AF-17, Homo sapiens, 1093 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P08473 (NEP_HUMAN), Neprilysin, EC 3.4.24.11, common acute lymphocytic leukemia antigen, 750 aa, single reviewed human record, primary gene name MME· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42303978Detection of MEN1 resistance mutations in cell-free DNA from acute leukemia patients treated with menin inhibitorsShukla N, et al. · Blood Cancer Journal 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCellosaurus cell line records CVCL_0064 (MV4-11), CVCL_0006 (THP-1), CVCL_1609 (NOMO-1), CVCL_2191 (SHI-1), CVCL_2119 (MOLM-13) and CVCL_7916 (MOLM-14), retrieved via the Cellosaurus APIBairoch A; SIB Swiss Institute of Bioinformatics · Cellosaurus 2026used by Monocyte — the graph's most-discussed undefined cell identity, and the confound sitting under its own DepMap haem signal, The monocytic confound is worse than recorded: two of the six rearranged lines are one patient, and the four-line control group contains a HOXA-driven fusion and two NPM1c/myelomonocytic lines
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.datasetQ154 gene-body class membership, margins and threshold sweepIqbal Lab oncofusion knowledge graph, beat Q154 · this project 2026used by Most gene-body 'AFF1-exclusive' calls in GSE252378 are a fold-change threshold cutting an oncoprotein-level gradient - and IRX1 is the one member where the non-AFF1 samples are genuinely at background, Six gene bodies are AFF1-exclusive and recurrent at gene scale; the authors' own pipeline confirms one of them, refutes three and has never measured two - and IRX1 is the one it confirms
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.reviewPMID 42489798Incorporating Immunotherapies into the Evolving Standard of Care for Pediatric B-Cell Precursor Acute Lymphoblastic Leukemia.Lissat A, Brivio E, Stutterheim J, et al. · Paediatr Drugs 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseDepMap CRISPR gene-effect (Chronos) for MRE11, served by the Open Targets Platform GraphQL APIBroad Institute DepMap / Open Targets Platform · Open Targets Platform 26.06 (meta.dataVersion year 26 month 06), fetched 2026-09-22 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q96DH6 (MSI2H_HUMAN), human MSI2, 328 aa· UniProt Consortium 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q68DK7 (MSL1_HUMAN), Male-specific lethal 1 homolog· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for MSL1 and the MSL complex against KMT2A, MLL and leukaemia, run for interactome round 5· NCBI PubMed, queried 2026-09-19 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databaseused by MTA2 / MTA1L1 (O94776) - the NuRD scaffold that clamps HDAC1, recruited in T lymphocytes by BCL11B, and absent together with MTA1 and MTA3 from every column of the pan-MLL-fusion interactome, No experiment has ever ASKED whether MTA2, MBD3, GATAD2A or SIN3A binds a KMT2A fusion - four of them were nonetheless in the lysate of a seven-fusion pulldown, and the class of that absence is measured-not-reported, not never-measured
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P11586 (C1TC_HUMAN), C-1-tetrahydrofolate synthase, cytoplasmicUniProt Consortium · UniProt 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P13995 (MTDC_HUMAN), Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrialUniProt Consortium · UniProt 2026
- weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseCell Ontology term lookup via the EMBL-EBI Ontology Lookup Service OLS4 APIEMBL-EBI Ontology Lookup Service; Cell Ontology consortium · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P10242 (MYB_HUMAN), Transcriptional activator Myb· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42014858HDAC8 inhibition targets STAT3-MYC axis and synergizes with Venetoclax in KMT2A-rearranged acute myeloid leukemiaZhang L, ..., Kuo YH · Leukemia 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.trial_registryA Phase I Study Investigating the Combination of the Menin Inhibitor Ziftomenib With Venetoclax and Gemtuzumab in Pediatric Patients With Acute Myeloid LeukemiaM.D. Anderson Cancer Center · ClinicalTrials.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P35749 (MYH11_HUMAN): reviewed sequence, length and positional feature annotationsUniProt Consortium · UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databasePDB 9FU2 'Smooth Muscle Myosin II in complex with MT-228' (title retrieved and verified at RCSB; released 2025)RCSB Protein Data Bank (entry metadata retrieved and title verified) · RCSB PDB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseAlphaFold Protein Structure Database entry for P35749 (model AF-P35749-F1)Jumper J, Varadi M, et al.; EMBL-EBI/DeepMind · AlphaFold DB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databasePDB 9FU2 'Smooth Muscle Myosin II in complex with MT-228': observed-residue ranges from the RCSB polymer entity instance record for chain ARCSB Protein Data Bank (entry and instance metadata retrieved and read back) · RCSB PDB 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseInterPro member-database domain matches for UniProt P35749 (Pfam, PROSITE, SMART, CDD, CATH-Gene3D, SUPERFAMILY)InterPro Consortium; EMBL-EBI · InterPro 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB entry P35579 (MYH9_HUMAN, Myosin-9)· UniProtKB/Swiss-Prot 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB O00160 (MYO1F_HUMAN) Unconventional myosin-If, Homo sapiens, 1098 aaUniProt Consortium · UniProtKB 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paperPMID 42085640Toxicity from asparaginase during acute lymphoblastic leukemia induction: a report from the Children's Oncology Group.Orgel E, Maese LD, Devidas M, Militano O, Rau RE, Angiolillo AL, et al. · Blood Adv 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseDepMap CRISPR gene-effect (Chronos) for NBN, served by the Open Targets Platform GraphQL APIBroad Institute DepMap / Open Targets Platform · Open Targets Platform 26.06 (meta.dataVersion year 26 month 06), fetched 2026-09-22 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseTARGET — Therapeutically Applicable Research to Generate Effective Treatments (NCI Center for Cancer Genomics programme page)National Cancer Institute, Center for Cancer Genomics / Office of Cancer Genomics · cancer.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseGDC Projects API query for program.name = TARGET, returning project_id, name, summary.case_count and summary.file_count for all TARGET projectsNCI Genomic Data Commons · api.gdc.cancer.gov 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databaseUsing TARGET Data (NCI Center for Cancer Genomics)National Cancer Institute, Center for Cancer Genomics · cancer.gov 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.datasetNCBI PubMed E-utilities esearch with querytranslation inspected, and UniProtKB reviewed human record Q14686 (NCOA6); queries run 2026-09-20 by this projectNCBI PubMed; UniProt Consortium; queries run by this project · Database 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.trial_registryA Phase 1/2 Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of SNDX-5613 in Patients With Colorectal Cancer and Other Solid Tumors· ClinicalTrials.gov 2026used by NCT05631574 (COVALENT-102): the third solid-tumour menin-inhibitor trial, missing from this graph because its drug is called BMF-219 - terminated after 13 patients for a strategic reason, explicitly NOT for efficacy or safety, No menin inhibitor has ever enrolled a KMT2A-rearranged solid tumour, and the one solid-tumour menin trial that read out was terminated for lack of efficacy, The predictable clinical error this beat exists to prevent: a menin inhibitor given for a KMT2A-rearranged sarcoma because of the gene name
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.analysisAldehyde versus replication: co-dependency test of the Fanconi ubiquitin-transfer module across 54 leukaemia lines· Oncofusion knowledge graph (internal analysis) 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB records Q9H3P2 (NELFA), Q8WX92 (NELFB), Q8IXH7 (NELFCD) and P18615 (NELFE)· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026used by NELF — the brake that has to come off for elongation, absent from the KMT2A literature, and less required in KMT2A-rearranged lines than in any other leukaemia, NELFE (RDBP) — the RNA-binding subunit of the pausing brake, and the alias that inflated a record count fifty-fold before it was caught
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB Q8WX92 (NELFB_HUMAN), Negative elongation factor B· UniProt Knowledgebase, reviewed (Swiss-Prot) 2026
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.databasePubMed E-utilities esearch record counts for NELFE and its aliases against KMT2A and MLL, with and without the two-letter alias RD, run for this beat· NCBI PubMed, queried 2026-09-19 2026
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paperPMID 42440143The clinical relevance of RAS pathway gene mutations in childhood B-cell acute lymphoblastic leukemia.Chen X, Gao L, Zhang Y, et al. · Annals of Hematology 2026used by NF1 - the only tumour-suppressor loss in this disease, and it is a deletion, so a mutation panel cannot see it, NRAS - the other RAS, the one whose 0.3% clone came back, and a UniProt record that lists HRAS1 as its own synonym, PTPN11/SHP2 - non-recurrent in infant KMT2A-rearranged ALL, well drugged everywhere else, and the one leukaemia trial that carried a SHP2 inhibitor was withdrawn, The RAS-mutant subclone is where the leukaemia goes, not what it is - a dissemination modifier that a marrow aspirate systematically under-counts
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.databaseUniProtKB P21359 (NF1_HUMAN), SUBCELLULAR LOCATION comments, NLS feature and TISSUE SPECIFICITY, fetched live 2026-09-21UniProt Consortium · Databases 2026
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database
- established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
- strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.databasePubMed counted-absence search for NFKB2 aliases against KMT2A/MLL, run 2026-09-20· PubMed (NCBI) 2026