SIN3A (Q96ST3) - the scaffold of the OTHER HDAC1/2 corepressor complex, a 5' fusion partner in infant B-ALL and in myelodysplasia, and present in three MLL-fusion AP-MS columns but not the index fusion's

No three-dimensional model is available for this protein, so the map above is the whole picture. That is itself informative: AlphaFold does not model chains this long, and the parts that have been crystallised are held under the entries for the individual domains.

• SIN3A is a strong pan-essential in DepMap - mean CHRONOS -0.883 across the whole panel - and KMT2A-rearranged lines are LESS dependent on it than other leukaemia lines are. Inhibiting it would be least selective exactly where this project wants selectivity.
• The scaffold has no catalytic site, no ligand pocket and ZERO experimental structures. There is nothing to design against, and the only tractable part of the complex is HDAC1/2 - which belongs to at least five complexes and is therefore the least selective handle available.
• An HDAC inhibitor given for a Sin3 hypothesis also engages NuRD, NCoR, CoREST and MiDAC. This graph should not carry an HDAC1/2 intervention as complex-directed unless the proposal names how complex selectivity would be achieved and demonstrated.
• In the one haematopoietic system where SIN3A's mark readout has been measured, Sin3a/HDAC1 is the REPRESSIVE arm that a WDR5/MLL coactivator complex replaces at differentiation. Removing Sin3A in a leukaemia could therefore push cells toward the activating state the fusion already imposes, not away from it.
• SIN3A is a NUTM1 fusion partner in an infant whose leukaemia was cured by standard chemotherapy. Any argument that the Sin3 axis is a therapeutic target in infant B-ALL has to explain why the one case in which it is genetically broken did well.

1. HDAC1 and ARID4B are annotated to the SAME region of the human SIN3A scaffold, 687-829. Do they compete? If ARID4B displaces HDAC1 there, then the KMT2A-r CRISPR dependency on ARID4B might act by REMOVING deacetylase from the scaffold rather than by delivering it, which inverts the expected mechanism and is testable by co-IP with a 687-829 deletion.
2. Does SIN3A appear in the MLL-AF4 pulldown below the top-300 cut? It scores under three other baits with 20-28 spectra, so a re-search of the public PXD009338 files for SIN3A peptides in the MLL-AF4 run would turn a measured-not-reported absence into a number, and the answer decides whether the index fusion is genuinely different or merely ranked lower.
3. Is the SIN3A::NUTM1 fusion protein a NuRD/Sin3 hijack or a NUTM1-p300 hijack with an incidental 5' end? Every characterised NUTM1 fusion works through p300-driven hyperacetylation irrespective of the 5' partner, which would make the SIN3A moiety a delivery address - and if so, where does it deliver? Nobody has mapped it.
4. Why is SIN3A less essential in KMT2A-rearranged lines than in other leukaemia lines? The difference is small but the direction is consistent, and a fusion that displaces a Sin3/HDAC corepressor (as the RUNX1 switch would predict) would produce exactly this sign.
5. Does a Sin3-selective or NCoR-selective HDAC inhibitor behave differently from a pan-HDAC1/2 inhibitor in a t(4;11) line? The chemoproteomic work says the complexes are pharmacologically distinguishable; nobody has used that in this disease.

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

   The mammalian transcriptional repressor Sin3 (mSin3) exists in a complex with the histone deacetylases HDAC1 and HDAC2 plus at least five tightly associated polypeptides, including the novel components SAP18 and SAP30, and SAP18 interacts directly with mSin3 and represses transcription when tethered to a promoter.

   Histone deacetylases and SAP18, a novel polypeptide, are components of a human Sin3 complex. · Zhang Y, Iratni R, Erdjument-Bromage H, Tempst P, Reinberg D · Cell 1997
   PMID 9150135DOI
   ▸What this evidence cannot show

   1997 biochemistry in HeLa cells, read from the abstract. It establishes co-complex membership, not stoichiometry or architecture, and predates the modern Sin3 subunit inventory - SUDS3/SDS3, ARID4A/B, ING1/2, BRMS1/BRMS1L, PHF12 and MORF4L1 are all later additions, so the 17-member list scored in E3 is my own curation and not this paper's. Nothing here concerns leukaemia or any fusion.

   ▸Evidence that argues against this (1)

   • The Sin3 subunit list this paper starts has proved unstable in a way that matters for my measurement: SAP30 and SAP18 - two of the three components it names - are BOTH ABSENT from the Skucha 960-protein network, as is SIN3B, while the four subunits that ARE present (SIN3A, SUDS3, ARID4B, ING2) are not the ones this paper identifies. So the four hits are not 'the Sin3 complex' in this paper's sense, and 4 of 17 should not be read as a complex-level recovery. This repository 2026
2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

   HDAC1, HDAC2 and the histone-binding proteins RbAp48 (RBBP4) and RbAp46 (RBBP7) form a core complex SHARED between NuRD and Sin3-histone deacetylase complexes, and the histone deacetylase activity of that isolated core complex is severely compromised; the NuRD-specific subunits MTA2 and MBD3 modulate it and mediate its assembly respectively.

   Analysis of the NuRD subunits reveals a histone deacetylase core complex and a connection with DNA methylation. · Zhang Y, Ng HH, Erdjument-Bromage H, Tempst P, Bird A, Reinberg D · Genes & Development 1999
   PMID 10444591DOI
   ▸What this evidence cannot show

   Biochemical purification from HeLa nuclear extract, 1999, read from the abstract. 'Shared core' describes co-purifying polypeptide composition; it does not establish that one physical particle interconverts between the two complexes, nor the fraction of cellular HDAC1/2 in each. Nothing about leukaemia or fusions.

   ▸Evidence that argues against this (1)

   • A chemoproteomic census of HDAC1/2 complexes finds MORE than the two this paper contrasts - NCoR, CoREST and MiDAC as well - and shows they respond differently to the same inhibitors. So 'shared between NuRD and Sin3' understates the sharing, and the NuRD-versus-Sin3 dichotomy this entry is built around is itself a simplification of a five-way ambiguity. Bantscheff M et al. 2011
3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

   SIN3A is present in the Skucha 2018 960-protein pan-MLL-fusion AP-MS network (UniProt Q96ST3, negative control 1|2) in three of seven bait columns - MLL-AF9 p = 0.0452 (20|19), MLL-EEN p = 0.0222 (28|31), MLL-ENL p = 0.0103 (28|23) - and is ABSENT from the MLL-AF4 (= KMT2A::AFF1) column; the Sin3/HDAC complex scores 4 of 17 subunits overall (SIN3A, SUDS3, ARID4B, ING2, all Sin3-specific) with the four subunits shared with NuRD at 0 of 4, and 0 of 17 in the MLL-AF4 column.

   NuRD sub-module split and Sin3/HDAC scoring over Skucha 2018 Supplementary Table 5 (PMID 29777171), run 2026-09-24: analyses/q193-nurd-module-split/run.py, with load-time assertions on sheet layout and a 960-row count; per-member accessions, bait columns, p-values, spectral counts and negative-control counts persisted in results.json. · This repository (script and results.json committed) 2026
   ▸What this evidence cannot show

   The accession in the table, Q96ST3, matches the one UniProt returns live for gene_exact:SIN3A AND organism_id:9606 AND reviewed:true (2026-09-24), so the row is the right protein. THE NEGATIVE CONTROL IS NON-ZERO (1|2), which puts SIN3A in the same weakened category as CHD4's 2|2 - a 1,273-residue abundant nuclear scaffold is a plausible AP-MS passenger. Absence from the MLL-AF4 column is measured-not-reported, not a zero: the table keeps the ~291 most significant preys for that bait and the raw files are public at PXD009338. Host is JURKAT T-ALL with a doxycycline-induced Strep-HA bait. The 17-member Sin3 list is my curation, written out in the script.

   ▸Evidence that argues against this (1)

   • The strongest argument against reading these four rows as a Sin3 signal is the negative control on the same table: CCT/TRiC, a canonical affinity-purification contaminant, scores 8 of 9 subunits at p = 2.0e-10 and appears in 8 of 8 MLL-AF4 slots - orders of magnitude above the Sin3 row's p = 0.007 and with far better bait coverage. If the strongest complex signal in the dataset is an artefact, a 4-of-17 with a non-zero control on the scaffold is well within artefact range. Skucha A et al. 2018
4. E4moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   ARID4B, a component of the SIN3A transcriptional corepressor complex, was identified and validated as one of three novel molecular vulnerabilities in KMT2A-rearranged ALL by CRISPR-Cas9 epigenome and kinome library screens in SEM (KMT2A::AFF1), ALL-PO (KMT2A::AFF1) and KOPN-8 (KMT2A::MLLT1) against KMT2A-wildtype comparators 697 and NALM-6, alongside MBD3 and BMPR2.

   CRISPR-Cas9 Library Screening Identifies Novel Molecular Vulnerabilities in KMT2A-Rearranged Acute Lymphoblastic Leukemia. · Schneider P, Wander P, Arentsen-Peters STCJM, Vrenken KS, Rockx-Brouwer D, Adriaanse FRS, Hoeve V, Paassen I, Drost J, Pieters R, Stam RW · International Journal of Molecular Sciences 2023
   PMID 37686014DOI
   ▸What this evidence cannot show

   THE MCP TOOL'S RENDERING, NOT PUBMED, DELETES ITALICISED SYMBOLS, and the raw PubMed abstract does contain ARID4B (efetch XML, 2026-10-03) - but it does NOT contain SIN3A, which appears nowhere in the abstract, so an auditor searching title/abstract for SIN3A will not find this paper for a different and real reason. The original caveat said both names were read from the PMC full text and the record's keyword list on 2026-09-24; the keyword list holds ARID4B but not SIN3A (checked 2026-10-03), so SIN3A's presence in this paper rests on the full text alone. The paper's own framing of ARID4B is that 'it functions as a component of the SIN3A transcriptional corepressor complex' - a background statement, not a measurement in this paper, and the screen tested ARID4B, NOT SIN3A itself. Cell lines only, no primary sample, no xenograft, no normal haematopoietic comparator. I did not read effect sizes or replicate counts for ARID4B specifically. IJMS is a lower-scrutiny venue than the other primary sources here.

   ▸Evidence that argues against this (1)

   • The screen's hit is ARID4B and not SIN3A, and the two behave OPPOSITELY in DepMap: ARID4B ranks 11,283 with a difference of +0.016 while SIN3A is a strong pan-essential at -0.883 that is marginally LESS essential in KMT2A-rearranged lines. So a reader must not carry an ARID4B dependency across to SIN3A - complex membership does not transfer a dependency any more than it transfers an interaction, and this entry's whole argument is that the scaffold is what differs. DepMap via this repository 2026
5. E5weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper

   A SIN3A::NUTM1 fusion has been reported in infant B-ALL, with durable molecular remission on standard acute lymphoblastic leukaemia chemotherapy; it is a twelfth reported 5' NUTM1 partner, absent from the 2025 eleven-partner literature review.

   A Rare Case of Infant B-ALL With SIN3A::NUTM1 Fusion: Durable Molecular Remission Achieved With Standard Acute Lymphoblastic Leukemia Chemotherapy · Peng D, Luo M, Lin Z, Chen S, Kuang Y, Fu X, Yao Q · Pediatric Blood & Cancer 2026
   PMID 41878999DOI
   ▸What this evidence cannot show

   TITLE-ONLY. This is a Letter with NO ABSTRACT indexed in PubMed and no open-access full text; the title, journal, year, authors, PMID and DOI were read from the efetch record on 2026-09-24 and the title alone carries the claim. Consequently support_location is recorded as 'abstract' only because no 'title' value exists in the corpus vocabulary - there IS no abstract to search, and an auditor should expect the terms in the title. The breakpoints, immunophenotype, follow-up duration and the meaning of 'durable' are all UNREAD and must not be cited. This graph's disease-nutm1-r-b-all already carries this citation with the same caveat; I did not re-derive it, I read that entry.

   ▸Evidence that argues against this (1)

   • A single favourable case report adds nothing to subtype-level prognosis and is subject to publication bias; the same subtype has a published poor-outcome case report pulling the other way. More importantly for this entry, a gene being a fusion PARTNER says nothing about whether the wild-type protein interacts with a different fusion - SIN3A::NUTM1 is not evidence about SIN3A and KMT2A::AFF1, and this item must not be read that way. Chen X et al. 2025
6. E6moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

   A complex t(15;21)(q24;q22) joining RUNX1 to SIN3A and UBL7-AS1, with both breakpoints mapped at the nucleotide level, was identified in a patient with myelodysplasia and leads to concurrent downregulation of RUNX1 and its transcription-factor partner SIN3A; a second recurrent t(15;21)(q21;q22) juxtaposes RUNX1 and TCF12 in three myeloid leukaemia cases.

   t(15;21) translocations leading to the concurrent downregulation of RUNX1 and its transcription factor partner genes SIN3A and TCF12 in myeloid disorders. · L'Abbate A, Tolomeo D, De Astis F, Lonoce A, Lo Cunsolo C, Muhlematter D, Schoumans J, Vandenberghe P, Van Hoof A, Palumbo O, Carella M, Mazza T, Storlazzi CT · Molecular Cancer 2015
   PMID 26671595DOI
   ▸What this evidence cannot show

   ONE PATIENT for the SIN3A translocation - the recurrent arm of this paper is the RUNX1-TCF12 rearrangement in three cases, not the SIN3A one. Read from the abstract. The mechanism proposed is LOSS of both genes, i.e. tumour-suppressor inactivation, and the authors describe a pathogenetic role as speculation ('we speculate'). Myelodysplasia in an adult, not infant B-ALL. This is NOT an analogy to a KMT2A gain-of-function fusion and must not be cited as one.

   ▸Evidence that argues against this (1)

   • The same gene is a fusion partner in two diseases with OPPOSITE proposed mechanisms - loss-of-function downregulation here, and a NUTM1 chimera with a favourable outcome in infant B-ALL - which means 'SIN3A is a recurrent fusion partner in leukaemia' is a statement with no consistent mechanistic content. A reader should take from these two items only that the locus is rearranged, not that a pathway is implicated. Peng D et al. 2026
7. E7moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

   In this project's genome-wide DepMap KMT2A-selectivity scan SIN3A ranks 17,096 of 17,728 with a difference of +0.1112: mean CHRONOS -0.758 in KMT2A-rearranged lines against -0.869 in other leukaemia lines, on a pan-essentiality of -0.883 - a strong dependency in BOTH arms that is marginally weaker in the KMT2A-rearranged arm.

   DepMap KMT2A-selective dependency scan over 17,728 genes: analyses/depmap-kmt2a-selective-scan-full/results.json, generated 2026-09-19. SIN3A rank 17,096, difference +0.1112, mean_kmt2a_r -0.7580, mean_other -0.8691, pan_essentiality -0.8829. · DepMap via this repository 2026
   ▸What this evidence cannot show

   UNLIKE MBD3's RANK, THIS ONE IS NOT FLOOR-COMPRESSED and should be read as real: both arm means are strongly negative, so SIN3A is a genuine dependency everywhere and the +0.111 is a small difference between two large effects. That makes it an argument against a KMT2A-SELECTIVE hypothesis, not against SIN3A mattering. Three standing caveats still apply: the scan fixes both arms from the first gene with data and drops 5 of 16 eligible KMT2A-rearranged lines; it reports a uniform n_all_lines of 1,208 for every gene when DepMap screens each gene in a gene-specific set; and it records no DepMap release, only a generation date (rule 83). Re-read from results.json on 2026-09-24 rather than quoted from ana-interactome4-enumeration, which carries the same figure.

   ▸Evidence that argues against this (1)

   • A pan-essential score in immortalised cell lines is a poor guide to what a drug would do, and this graph has already recorded the general form of the objection: high constraint or broad essentiality says a gene matters for viability, not that partial reversible inhibition in a patient is unsafe or ineffective. The opposite reading is equally available - a gene essential in every leukaemia line is a gene whose inhibition has no therapeutic window, which is the reason the corpus's earlier enumeration rejected SIN3A outright. This repository 2026
8. E8strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   HDAC1/2-containing complexes are scaffolded by ELM-SANT domain subunits and comprise at least NuRD, Sin3, NCoR, CoREST and a mitotic deacetylase complex (MiDAC); sixteen HDAC inhibitors cluster by which of these complexes they engage, with aminobenzamides binding the HDAC-NCoR complex more strongly than the HDAC-Sin3 complex, so HDAC inhibitor selectivity must be evaluated in the context of complexes rather than purified catalytic subunits.

   Chemoproteomics profiling of HDAC inhibitors reveals selective targeting of HDAC complexes. · Bantscheff M, Hopf C, Savitski MM, Dittmann A, Grandi P, Michon AM, Schlegl J, Abraham Y, Becher I, et al. · Nature Biotechnology 2011
   PMID 21258344DOI
   ▸What this evidence cannot show

   Affinity capture plus quantitative mass spectrometry in cell extracts, 2011; read from the abstract. The cell systems are not named there and none is stated to be leukaemic; the expected_absent_terms are deliberate - nothing in this paper concerns KMT2A or MLL, and it is cited here only for the claim that HDAC1/2 membership is multi-complex and pharmacologically resolvable. Affinity-matrix chemoproteomics reports what binds an immobilised ligand, which is not the same as target engagement in a cell.

   ▸Evidence that argues against this (1)

   • That complexes are pharmacologically distinguishable in a chemoproteomic assay does not mean any approved HDAC inhibitor achieves complex selectivity at a tolerated dose in a patient, and no clinical HDAC inhibitor is marketed on complex selectivity. So the paper's constructive half - that one could target a complex rather than a subunit - remains a demonstration in extracts, and the destructive half, that subunit-level selectivity claims are meaningless, is the part that is safe to rely on. Bantscheff M et al. 2011
9. E9strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

   SIN3A is a functional component of a RUNX1 corepressor complex in human haematopoietic progenitor cells: PRMT6 is recruited by RUNX1 into a complex containing Sin3a and HDAC1, deposits H3R2me2a at megakaryocytic genes and holds RUNX1 target genes in an intermediate state carrying both H3K27me3 and H3K4me2 but not H3K4me3; on megakaryocytic differentiation PRMT6 binding is lost, the H3R2me2a mark decreases and a coactivator complex containing WDR5/MLL and p300/pCAF is recruited, raising H3K4me3 and H3K9ac.

   Histone arginine methylation keeps RUNX1 target genes in an intermediate state. · Herglotz J, Kuvardina ON, Kolodziej S, Kumar A, Hussong H, Grez M, Lausen J · Oncogene 2012
   PMID 22777353DOI
   ▸What this evidence cannot show

   K562 and human haematopoietic progenitors, megakaryocytic differentiation - haematopoietic but NOT lymphoid and not leukaemic-fusion-driven. Read from the abstract. THE 'MLL' IN THIS PAPER IS WILD-TYPE MLL IN A WDR5-containing COACTIVATOR COMPLEX, on the ACTIVATING side of the switch, and is not a fusion protein: this item must never be cited as SIN3A interacting with an MLL fusion. It is the only result in this entry that places SIN3A and HDAC1 in a haematopoietic corepressor complex with a measured histone-mark readout, which is why it is here.

   ▸Evidence that argues against this (1)

   • This result cuts AGAINST any Sin3-plus-KMT2A-fusion story rather than for it: the Sin3a/HDAC1 corepressor and the WDR5/MLL coactivator are on OPPOSITE sides of the same switch, and they are mutually exclusive in time - Sin3a/HDAC1/PRMT6 holds the genes down and the WDR5/MLL complex replaces it to turn them on. If a KMT2A fusion behaves like the coactivator arm, Sin3A is the thing it displaces, not the thing it recruits. Herglotz J et al. 2012
10. E10moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    SIN3A's only documented subnuclear address is conditional and partner-driven: SAP30L interacts with several components of the Sin3A corepressor complex, binds the PAH3/HID region of MOUSE Sin3A, carries a functional nucleolar localisation signal, and SAP30L and SAP30 are able to target Sin3A to the nucleolus.

    SAP30L interacts with members of the Sin3A corepressor complex and targets Sin3A to the nucleolus. · Viiri KM, Korkeamaki H, Kukkonen MK, Nieminen LK, Lindfors K, Peterson P, Maki M, Kainulainen H, Lohi O · Nucleic Acids Research 2006
    PMID 16820529DOI
    ▸What this evidence cannot show

    SPECIES AND SUBJECT TRAP, and this entry handles it explicitly. The paper is about SAP30L, not SIN3A; the residues '120-140' in its abstract are SAP30L's, and the Sin3A whose PAH3/HID they bind is MOUSE. NO RESIDUE NUMBER FROM THIS PAPER IS QUOTED ANYWHERE IN THIS ENTRY - every coordinate here is from the human Q96ST3 feature table, confirmed by string match against the downloaded 1,273-residue sequence. The nucleolar targeting is also an overexpression result in unnamed cell lines, and UniProt cites this single paper for both of SIN3A's location comments. Read from the abstract.

    ▸Evidence that argues against this (1)

    • The subunits that drive this nucleolar relocalisation, SAP30 and SAP30L, are BOTH absent from the Skucha MLL-fusion network, so the only documented subnuclear address for SIN3A depends on a component this dataset does not recover. Taken with the fact that a partner-dependent address is not a constitutive one, this means SIN3A should be treated as having NO established subnuclear localisation in a haematopoietic or leukaemic cell. This repository 2026
11. E11moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

    A bounded literature search on 2026-09-24 returns 2 records for SIN3A with MLL in title or abstract and 2 for SIN3A with KMT2A, against a positive control of 55 for MEN1 with MLL; none of the four describes SIN3A in a KMT2A-fusion leukaemia - the MLL hits are the RUNX1/PRMT6 megakaryocytic paper and an unrelated H3R2me2s histone-mark paper, and the KMT2A hits are an IDH1/2 demethylase review and an exome pool-sequencing study of neurodevelopmental disorders in which SIN3A and KMT2A appear in the same gene list.

    NCBI esearch via scripts/pubmed_safe.py on 2026-09-24. SIN3A[tiab] AND MLL[tiab] -> 2 (PMIDs 22777353, 22231400). SIN3A[tiab] AND KMT2A[tiab] -> 2 (PMIDs 31221981, 29158550). SIN3A[tiab] AND leukemia[tiab] -> 21. SIN3A[tiab] AND NUTM1[tiab] -> 1 (41878999). Positive control MEN1[tiab] AND MLL[tiab] -> 55. · NCBI PubMed E-utilities 2026
    ▸What this evidence cannot show

    One tag per term (rule 94), querytranslation recorded, run through pubmed_safe so an empty translation raises rather than returning a false zero. ALL FOUR HITS WERE TITLE-CHECKED AND THREE WERE REJECTED: PMID 22231400 is about H3R2me2s and mentions MLL and Sin3a only as complex names in a SILAC interactor list; PMID 31221981 is an IDH1/2-KDM5C-KDM6A review; PMID 29158550 is Exome Pool-Seq in neurodevelopmental disorders, where SIN3A and KMT2A are two of 24 genes in a variant list and have no relationship to each other. Only PMID 22777353 is on-topic and it is haematopoietic rather than fusion biology. The 21 records for SIN3A with leukemia were NOT individually title-checked and that count should not be read as 21 on-topic papers.

    ▸Evidence that argues against this (1)

    • The literature bound understates the record in a way I can demonstrate: SIN3A HAS been assayed against seven MLL fusions by AP-MS and scored under three of them, and that measurement appears in none of these four literature records. The honest class for 'SIN3A and the index fusion' is measured-not-reported for the AP-MS column and never-measured for anything functional - not 'nobody has looked'. This repository 2026

• binds →HDAC1 - a class I eraser that has no dependency claim of its own in this disease, because removing it alone does nothing until HDAC2 goes too

  HDAC1 docks the human SIN3A scaffold at 687-829 (UniProt Q96ST3), the same region annotated for ARID4B

• binds →HDAC2 - the buffering half of the class I pair, and the one class I enzyme a drug result in acute leukaemia has actually been pinned to, in AML rather than in a KMT2A fusion

  mSin3 complex contains HDAC1 and HDAC2 plus SAP18/SAP30

• part of →RBBP4 - the shared histone-binding subunit that every leukaemia line needs, and whose identical-length paralogue cannot replace it

  RBBP4/RBBP7 are part of the HDAC1/2 core shared between Sin3/HDAC and NuRD

• causes →NUTM1-rearranged B-ALL - the KMT2A-wild-type arm of the same infant trials, with 4-year EFS of 100% against 36-37% next door

  SIN3A::NUTM1, the twelfth reported 5' NUTM1 partner, in infant B-ALL

• binds →KMT2A::MLLT3 (MLL-AF9), t(9;11)(p21.3;q23.3)

  present in the MLL-AF9 column of the Skucha AP-MS network, p = 0.0452, 20|19 spectra, neg ctrl 1|2

• related to →REST / NRSF - the transcription factor that delivers G9a to chromatin through MED19 and MED26, is a paediatric cancer gene, and is the worst search token in this corpus

  REST docks the SIN3A PAH domains; this graph's gene-rest already carries REST's SIN3A-interaction region (REST coordinates)

• ← supportsThe MLL-fusion interactome recovers corepressor SCAFFOLDS and not their HDAC1/2 catalytic core: NuRD splits 5/7 remodelling arm versus 0/7 deacetylase arm (Fisher p = 0.021), and HDAC1, HDAC2, RBBP4 and RBBP7 are absent from all seven baits

  Sin3/HDAC scores 4 of 17, all Sin3-specific; the shared HDAC1/2 core is 0 of 4

• ← related toHDAC1 and HDAC2 belong to at least five different corepressor complexes, so an HDAC1/2 observation names no complex - and this graph carried both enzymes without the scaffolds that would tell them apart

  the Sin3/HDAC side of the distinction

• ← part ofARID4B / SAP180 (Q4LE39) - the Sin3A-complex subunit that shares SIN3A's HDAC1-binding region, is in the MLL-fusion interactome, and is the second of only two epigenetic vulnerabilities a CRISPR screen found in KMT2A-rearranged ALL

  SAP180: subunit of the SIN3A corepressor complex; annotated to SIN3A 687-829 alongside HDAC1

• ← supportsNo 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

  no targeted experiment; scored under three non-index baits

• ← related toNo histone-mark readout has ever been measured after perturbing ANY NuRD or Sin3 subunit in a KMT2A-rearranged cell - the two complexes whose entire job is acetylation have zero acetylation data in this disease

  no mark readout exists for any of the 17 Sin3/HDAC subunits in a KMT2A-rearranged cell