BUD13 - a RES-complex splicing factor 1.66 Mb from KMT2A on 11q23.3, whose one chromatin paper puts it in the soluble fraction

This is real experimental data — atoms placed by crystallography or cryo-EM, deposited by the people who did the experiment.

• BUD13 is broadly essential across 1,208 DepMap lines (-0.682) with essentially no KMT2A selectivity (-0.048), so an intervention against it is loss of a core splicing machine in every tissue - the worst kind of essential-function liability in an infant.
• BUD13 is one of three RES subunits and one of more than fifty proteins in the activated spliceosome, so any pharmacological effect would be spliceosome inhibition rather than BUD13 inhibition, and spliceosome-directed agents have a well-known therapeutic index problem.
• If BUD13's relevance ran through the MINOR spliceosome, the closest disease precedent is ZRSR2 loss in myelodysplastic syndrome - a lesion associated with a clonal myeloid disorder rather than a therapeutic opportunity, so perturbing the same machine could as easily promote a second malignancy as treat one.
• The entire case for BUD13's relevance here is a single MI-score 0.27 proximity row in a cell line with no KMT2A rearrangement. If that row is a compartment artefact, there is nothing else, and the entry should be read as a bounded candidate rather than as a partner.

1. Is BUD13 on chromatin in a leukaemia cell? The single fractionation result that exists puts it in the soluble pool in HEK 293, and splicing is largely co-transcriptional, so the answer may be cell-type and transcription-rate dependent - and it decides whether the epigenetic not-applicable call survives.
2. Do U12-type intron-containing genes appear disproportionately in the KMT2A::AFF1 target set? BUD13 handles that intron class, ZRSR2 loss causes U12 retention in myeloid disease, and the intersection has never been computed - it needs no wet work.
3. Where in the nucleus is BUD13? It is placed in eleven spliceosome structures and in no microscopy: no speckle, nucleolar or condensate assignment was found, which for a spliceosomal protein is a gap this graph's speckle vocabulary could close with one co-stain.
4. The RES complex is BUD13, RBMX2 and SNIP1, and neither RBMX2 nor SNIP1 has an entry here. Does either appear in the same K562 proximity deposition, and does the complex as a unit sit nearer the KMT2A scaffold than BUD13 alone?
5. Is BUD13 expression correlated with KMT2A-rearrangement status only through copy number? The two genes are 1.66 Mb apart on 11q23.3, so any expression association has a structural confound that has never been controlled for.

1. E1established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

   UniProt Q9BRD0 is the single reviewed human BUD13 record at 619 aa (70,521 Da), a CWC26-family nuclear protein of the activated B/catalytic step-1 spliceosome and of the minor spliceosome that splices U12-type introns, almost entirely disordered with one coiled coil at 433-520, carrying no chromatin writer/eraser/reader module, with a Nucleus location comment supported by three ECO:0000269 experimental sources; BUD13 lies at chr11:116,748,170-116,773,039 on GRCh38, 1,663,417 bp from KMT2A's start at chr11:118,436,456.

   UniProtKB Q9BRD0 (BUD13_HUMAN) features, comments, PDB cross-references and subcellular-location evidence codes; HGNC:28199 via rest.genenames.org; Ensembl ENSG00000137656 and ENSG00000118058 GRCh38 coordinates via rest.ensembl.org; retrieved 2026-09-22 · UniProt Consortium / HGNC / Ensembl 2026
   ▸What this evidence cannot show

   Retrieved 2026-09-22. Two isoforms are annotated (Q9BRD0-1, Q9BRD0-2) and 619 aa is the canonical; RefSeq lists NP_116114.1 and NP_001153208.1 and their lengths were not checked, so every coordinate quoted is on the UniProt canonical frame. UniProt's minor-spliceosome membership cites PubMed 33509932, a 2.9-Angstrom cryo-EM structure of the activated human minor spliceosome whose ABSTRACT does not name BUD13 - so that membership is an entry in the structure's subunit table rather than a headline result of the cited paper, which is recorded here rather than presented as the paper's finding. The 1.66 Mb gap is arithmetic on two Ensembl records and is a statement about genome position only.

   ▸Evidence that argues against this (1)

   • UniProt's coded experimental annotations frequently point at a paper that is not about the annotated fact, which is demonstrable in this very record: the minor-spliceosome comment cites a cryo-EM structure paper whose abstract names SCNM1, RBM48-ARMC7, PPIL2 and CRIPT as the newly identified proteins and does not name BUD13 at all. Bai R et al. 2021
2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

   The single publication behind BUD13's presence in the interactome read queue is the 50-RBP BioID2 proximity map in K562 cells (IMEx IM-30059), in which no KMT2A-complex component, no super elongation complex component and no fusion protein is used as a bait, and KMT2A, MEN1, PSIP1, AFF1, AFF4, ELL, MLLT1, CDK9, CCNT1 and DOT1L appear only as prey.

   Systematic identification of post-transcriptional regulatory modules. · Khoroshkin M, Buyan A, Dodel M, et al. (22 authors; senior author Goodarzi H) · Nat Commun 2024
   PMID 39251607DOI
   ▸What this evidence cannot show

   One publication, one cell line, an overexpression BioID2 map, and the curated IMEx rows are the authors' filtered bona fide set rather than raw hit lists. K562 is BCR::ABL1 chronic myeloid leukaemia with no KMT2A rearrangement, so the KMT2A labelled is wild type and the menin labelled is in a cell with no menin-inhibitor-relevant fusion. This paper is already cited in 12 entries here including a dedicated analysis of the deposition, so its platform-level facts are restated deliberately rather than re-derived; the new content is the per-bait BUD13 reading.

   ▸Evidence that argues against this (1)

   • Proximity recovery is dominated by subcellular compartment occupancy rather than by binding, so recovery of nuclear proteins by a nuclear RNA-processing bait is the expected result of shared residency - and this graph's own audit of the same deposition found KMT2A recovered by 25 of the 50 baits, which makes KMT2A's appearance in any one bait's neighbourhood close to uninformative. Go CD et al. 2021
3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

   IntAct REST serves exactly two binary BUD13 rows against this graph's core scaffold - KMT2A and MEN1 - and both carry the SAME interaction accession EBI-56895223, differing only in binaryInteractionId, so they are one spoke-expanded n-ary proximity experiment rather than two observations; both are MI:1314 proximity-dependent biotin identification typed MI:2364 proximity at MI-score 0.27, in host organism Homo sapiens K562 myeloid leukemia cell, with BUD13 the bait.

   IntAct REST findInteractions/Q9BRD0 (673 indexed interactions), filtered to Q03164/O00255/O75475/Q9UHB7/Q8TEK3/P51825/Q03111/P42568/P55199/P55197 with ac, binaryInteractionId, experimentalRole, detectionMethod and hostOrganism read per row; retrieved 2026-09-22 · IntAct molecular interaction database (EMBL-EBI) 2026
   ▸What this evidence cannot show

   Retrieved 2026-09-22. MI-score 0.27 is the lowest band IntAct assigns. The spoke expansion was identified because the same accession EBI-56895223 also returns a BUD13-BUD13 self pair, which is how the n-ary structure was diagnosed rather than assumed. The queue's n_baits of 2 is therefore not two independent observations, and the reading 'KMT2A and MEN1 in one experiment' is a statement about one bait's labelled neighbourhood, not about a shared complex.

   ▸Evidence that argues against this (1)

   • Recovering KMT2A and MEN1 together in one proximity experiment is the least surprising possible pair, because menin and KMT2A are constitutive partners at a well-characterised interface - so their co-appearance in a bait's neighbourhood adds no evidence beyond the appearance of either one, and reading it as two prey is double-counting a single complex. Yokoyama A et al. 2005
4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   In multiple-cell-compartment affinity purification with mass spectrometry, BUD13 - together with other RNA-binding proteins and spliceosomal and ribosomal subunits - associates with Kin17 in the SOLUBLE fraction, while the Kin17-METTL22 interaction was confirmed in both the soluble and the chromatin fractions; so in the one assay that could distinguish chromatin from soluble, BUD13 came out soluble.

   Methylation of the DNA/RNA-binding protein Kin17 by METTL22 affects its association with chromatin. · Cloutier P, Lavallee-Adam M, Faubert D, et al. (5 authors; senior author Coulombe B) · J Proteomics 2014
   PMID 24140279DOI
   ▸What this evidence cannot show

   This paper is about Kin17 and METTL22, not about BUD13; BUD13 appears as one of many co-purifying RNA-binding proteins, so the soluble-fraction assignment is a by-product of somebody else's experiment. The cells are HEK 293, not haematopoietic. A biochemical fractionation is a crude separation and a protein can be genuinely chromatin-associated and still partition largely soluble, especially a splicing factor released by nuclease treatment. Read as abstract and title. This is the ONLY paper that places BUD13 in a chromatin experiment at all, so the absence rests on a single indirect source.

   ▸Evidence that argues against this (1)

   • Splicing is largely co-transcriptional, so spliceosomal components are functionally chromatin-proximal even when biochemical fractionation puts them in the soluble pool - and the minor spliceosome in particular acts on nascent transcripts, which means a soluble-fraction assignment does not exclude action at the gene. Bai R et al. 2021
5. E5strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.dataset

   BUD13 is broadly essential but not KMT2A-selective: mean DepMap gene effect -0.682 across 1,208 lines, -0.6524 in 11 KMT2A-rearranged leukaemia lines versus -0.6044 in 43 other leukaemia lines, a difference of -0.048 placing it at rank 3,643 of 17,728.

   analyses/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
   ▸What this evidence cannot show

   The reportable figure here is the absolute essentiality (-0.682, broadly essential) and the SIZE of the group difference (-0.048, negligible); the rank of 3,643 is not reported as a finding because roughly half of any gene set lies above the median of this scan by construction and this project's base rate is 45.3%. Group sizes of 11 and 43 are underpowered. The stored scan records a compute date and NOT a DepMap release, so it cannot be told from quarterly drift.

   ▸Evidence that argues against this (1)

   • A broadly essential splicing factor's knockout phenotype is dominated by general spliceosome failure, so a between-subtype comparison of gene effect measures how tolerant each panel is of loss of splicing rather than anything specific to the fusion - and the same scan puts the KMT2A-rearranged and other-leukaemia means within 0.05 of each other, which is the expected result for a housekeeping machine. DepMap (Broad Institute), via this repository's scan 2026
6. E6strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.database

   BUD13 has no leukaemia and no KMT2A literature - BUD13[tiab] AND leukemia[tiab] = 0, AND KMT2A[tiab] = 0, AND MLL[tiab] = 0, AND chromatin[tiab] = 1, AND histone[tiab] = 2 - and its literature is dominated by a metabolic GWAS locus: of 83 BUD13[tiab] records, 25 concern triglycerides against 17 concerning splicing.

   NCBI E-utilities esearch, db=pubmed, querytranslation read back from every response, run 2026-09-22 · NCBI PubMed 2026
   ▸What this evidence cannot show

   All queries are one tag per term and never a parenthesised group; each querytranslation was read back and all were clean, e.g. "BUD13"[Title/Abstract] AND "leukemia"[Title/Abstract]. Positive operand controls through the identical code path: BUD13[tiab] = 83, BUD13[tiab] AND splicing[tiab] = 17, BUD13[tiab] AND RES complex[tiab] = 8, H3K79me2[tiab] = 224 - so the zeros are not instrument failures. Note that BUD13[tiab] AND minor spliceosome[tiab] returns 0 even though UniProt asserts minor-spliceosome membership, which is a direct demonstration that these zeros bound titles and abstracts and not papers. Absence class: never-measured for the fusion-context question. The 25-of-83 triglyceride share is a count of records matching the word, not a hand-classification.

   ▸Evidence that argues against this (1)

   • A zero on BUD13 and the minor spliceosome, returned by the same instrument in the same run that returned 224 for a histone mark, is a worked demonstration inside this very evidence item that a title-and-abstract zero can coexist with a well-curated database assertion - so none of these zeros should be read as an absence of the underlying biology. NCBI PubMed / UniProt 2026

• related to →KMT2A / MLL1 — the gene that breaks

  BUD13-bait BioID2 in K562 recovered KMT2A as prey (MI:1314, MI-score 0.27); one n-ary record EBI-56895223

• related to →MEN1 / menin — the adaptor the fusion cannot work without

  same single BUD13-bait record recovered MEN1 - the only queue row putting KMT2A and menin in one experiment, in a leukaemia line

• supports →The 50-RBP BioID2 proximity map in K562 - the first modern proximity dataset this graph can reach, and AFF1 is in it as prey

  BUD13 is one of the 50 RBP baits; per-bait reading of a deposition characterised here only at platform level

• related to →ILF3 / NF90 - a nucleolar dsRNA-binding coactivator whose chromatin residency was mapped in the same leukaemia line that proximity-labelled KMT2A

  two of the 50 K562 BioID2 baits whose neighbourhoods contain the KMT2A scaffold; BUD13 recovered KMT2A+MEN1, ILF3 recovered KMT2A+PSIP1+ELL

• related to →Plain-English: chromatin and epigenetics — the sticky notes on the DNA, and which ones matter here

  no writer/eraser/reader module, and the one fractionation experiment puts BUD13 in the soluble not the chromatin pool

• related to →KMT2A::AFF1 (MLL-AF4), t(4;11)(q21;q23)

  BUD13 is an 11q23.3 gene 1.66 Mb from KMT2A and has NEVER been reported as a fusion partner - recorded so the cytoband is not misread as a breakpoint claim