Oncofusion

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Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q84-pan-fusion-core

SMARCC1 / BAF155 (Q92922) - the SWI/SNF core scaffold, in the pan-MLL-fusion core, and the missing gene entry in this graph's SWI/SNF beat

also called SMARCC1 · BAF155 · SRG3 · SWI/SNF complex subunit SMARCC1

SMARCC1 (BAF155) is one of the two scaffold proteins that hold every version of the SWI/SNF nucleosome-remodelling machine together. It co-purifies with all seven MLL fusions tested - putting an opening remodeller in the same purification as the closing one, CHD4.

The same thing, for a scientist

SMARCC1 (Q92922, 1,105 aa) is a core subunit of every mammalian SWI/SNF (BAF) complex - cBAF, PBAF and ncBAF alike - forming, with SMARCB1, SMARCE1 and a SMARCD paralogue, the core module onto which the ATPase is built. In Skucha 2018 it co-purified with all seven MLL fusions; the MLL-AF4 (= KMT2A::AFF1) call is p = 0.0707 with 5|4 spectra and a negative control of 1|0. **That p-value is above 0.05**, so this row is in the table only because the paper retained the top 300 per bait by rank, and it should not be described as a significant index-fusion interaction. This graph already has a SWI/SNF beat with entries for SMARCA2, SMARCA4, SMARCB1, SMARCD1 and SMARCD2 and a cBAF/PBAF/ncBAF concept entry, but none for the core scaffold; that beat independently ran `SMARCC1 AND (MLL OR KMT2A)`, got one record, fetched it and found it off-beat - a glioblastoma ASH2L CRISPR screen - which is exactly the result this beat reproduced.

Go deeper
The Skucha row, with its p-value stated plainly

7 of 7 fusions. MLL-AF1p 0.00155 (9|7), MLL-AF4 0.0707 (5|4), MLL-AF9 0.00245 (15|13), MLL-CBP 0.0245 (3|18), MLL-EEN 0.037 (16|10), MLL-ENL 0.0114 (10|12), MLL-GAS7 0.0255 (12|13); negative control 1|0 1. The index-fusion p is 0.0707 - above any conventional threshold. Six other baits are below 0.05 but none is strong. Of the twelve proteins in this beat, SMARCC1's pan-fusion evidence is among the flattest: consistently present, never compelling.

Two remodellers pointing opposite ways in the same purification

CHD4 (NuRD, nucleosome remodelling coupled to deacetylation, generally repressive) and SMARCC1 (BAF, generally opening) are both in the pan-fusion core of the same seven purifications, with CHD4 the stronger call by three to eight orders of magnitude at most baits. This graph should resist the temptation to build a story out of that. Nuclear lysate contains both machines in abundance; the honest statement is that two opposing remodelling complexes are each represented by a core component, that no other subunit of either complex is named anywhere in the paper's body text, and that neither is validated orthogonally.

What SMARCC1 does

SMARCC1 (BAF155) is part of the BAF core module with SMARCB1 (BAF47), SMARCE1 (BAF57) and SMARCD1/2/3 (BAF60A/B/C); co-expression and crystallography of SMARCC1 fragments with SMARCE1 and SMARCD1 define how that core assembles 2. Its abundance is itself regulated: methylated SMARCC1 and SMARCC2 are targeted for proteolysis by L3MBTL3 and CRL4-DCAF5, with LSD1 demethylating them to preserve complex integrity, and SMARCC1 is the critical target of that axis in embryonic stem cell self-renewal 3. That is relevant here because a protein whose steady-state level is set by a degradation switch is a protein whose presence in a purification can change with cell state.

Facts and figures
uniprotQ92922
length AA1105
accession resolutionResolved live 2026-09-21: gene_exact:SMARCC1 AND organism_id:9606 AND reviewed:true returns exactly one row, gene_primary SMARCC1, Q92922, SMRC1_HUMAN, 1,105 aa, synonym BAF155. Matches Skucha's table. Its paralogue SMARCC2/BAF170 is a separate accession of different length, so the length check discriminates them.
localizationNucleus, with a cytoplasmic pool
subnuclear localizationNot assigned to a named subnuclear body; chromatin-distributed as part of BAF.
localization evidenceUniProt Q92922, fetched 2026-09-21: Nucleus with ECO:0000269 and Cytoplasm with ECO:0000269. No subnuclear compartment annotation.
shown for fusionKMT2A::AFF1 (MLL-AF4) by co-purification only and at p = 0.0707, plus the six other Skucha baits. NO independent experiment ties SMARCC1 to a KMT2A fusion in any system.
graph contextThe SWI/SNF beat holds gene-smarca2, gene-smarca4, gene-smarcb1, gene-smarcd1, gene-smarcd2, concept-cbaf-pbaf-ncbaf-three-complexes, ana-swi-snf-enumeration-and-bounded-absences and ana-swi-snf-lineage-split-dependency-scan. SMARCC1 - the core scaffold shared by all three BAF subtypes - had no entry of its own; it was mentioned in six node files, all as a table row or a downstream gene.
skucha 2018
{
  "bait": "MLL-AF4 (= KMT2A::AFF1)",
  "p_value": 0.0707,
  "spectral_counts": "5|4",
  "n_fusions_of_seven": 7,
  "negative_control_counts": "1|0",
  "per_bait": {
    "MLL-AF1p": "0.00155 (9|7)",
    "MLL-AF4": "0.0707 (5|4)",
    "MLL-AF9": "0.00245 (15|13)",
    "MLL-CBP": "0.0245 (3|18)",
    "MLL-EEN": "0.037 (16|10)",
    "MLL-ENL": "0.0114 (10|12)",
    "MLL-GAS7": "0.0255 (12|13)"
  },
  "index_bait_warning": "p = 0.0707, above conventional significance; retained by the top-300-per-bait rank rule.",
  "source": "analyses/skucha-mll-fusion-interactome/results.json, re-derived from the cached MOESM4 xlsx on 2026-09-21"
}
cell types and states
[
  "Jurkat (human T-ALL) - AP-MS host, nuclear lysate",
  "mouse embryonic stem cells - SMARCC1 as the critical LSD1/L3MBTL3 target for self-renewal",
  "recombinant protein - core module crystallography",
  "no KMT2A-rearranged cell of any kind"
]
bounded literature
{
  "query": "SMARCC1[tiab] AND (KMT2A[tiab] OR MLL[tiab] OR \"MLL-AF4\"[tiab] OR \"MLL-AF9\"[tiab])",
  "querytranslation": "\"SMARCC1\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract] OR \"MLL-AF4\"[Title/Abstract] OR \"MLL-AF9\"[Title/Abstract])",
  "count": 1,
  "on_topic_after_title_check": 0,
  "date": "2026-09-21",
  "tool": "NCBI esearch db=pubmed",
  "rejected": "PMID 37974198, an epigenetic CRISPR screen in glioblastoma identifying ASH2L, in which SMARCC1 appears as a downstream downregulated gene - off-beat.",
  "alias_query": "BAF155[tiab] AND (KMT2A[tiab] OR MLL[tiab]) returns 0; querytranslation \"BAF155\"[Title/Abstract] AND (\"KMT2A\"[Title/Abstract] OR \"MLL\"[Title/Abstract])",
  "names_tried": [
    "SMARCC1",
    "BAF155"
  ],
  "positive_control": "the identical query shape with MEN1 returns 85",
  "independent_agreement": "This graph's SWI/SNF beat ran the same query in an earlier cycle, fetched the same single record and judged it off-beat. Two independent runs, same answer. That is corroboration, not a new finding.",
  "bound": "Titles and abstracts only; supporting figures not searched."
}
complex level evidence
{
  "_added": "king, cycle 48, 2026-09-21. analyses/mll-fusion-interactome-complexes/run.py",
  "what_this_adds": "Q84's caution in this entry is literally correct and its inference is now testable. It said no other subunit of either remodelling complex is named anywhere in the PAPER'S BODY TEXT -- true. But the paper's own supplementary table is data, and it contains five NuRD subunits and six BAF subunits. The complex-level claim the body text could not support, the table does.",
  "measured_in_the_960_protein_network": {
    "NuRD": "5 of 14 subunits: CHD3, CHD4, GATAD2A, GATAD2B, MBD2. Hypergeometric p = 3.5e-4 against a 20,000 proteome; 0.67 expected by chance. Median 5 of 7 baits.",
    "BAF_SWI_SNF": "6 of 17 subunits: PBRM1, SMARCA4, SMARCB1, SMARCC1, SMARCC2, SMARCE1. p = 9.4e-5; 0.82 expected. Median 5 of 7 baits."
  },
  "so_the_conclusion_changes_but_only_partly": "Neither complex is represented by a lone core component. Both bring several subunits, including CHD3 alongside CHD4 and SMARCC2 alongside SMARCC1. That is what a genuine complex-level association looks like and it is not what a single sticky protein looks like.",
  "the_reason_to_still_resist_the_story": "The single strongest complex signature in the whole analysis is the CCT/TRiC chaperonin, 8 of 9 subunits at p = 2.4e-10 -- a canonical affinity-purification contaminant that nobody believes is a specific partner. So complex-wide enrichment is NOT by itself evidence of specific binding, and the NuRD and BAF rows sit two to six orders of magnitude BELOW that artifact. The positive control behaves correctly (SEC, 10 of 16, p = 3.8e-10, with zero pan-fusion members because its members ARE the bait partners), which licenses reading the ranking -- but the original caution about orthogonal validation stands undiminished.",
  "background_caveat": "The background is the ~20,000-protein proteome, not the 4,600 proteins the study actually recovered before filtering, which is not in the table. That inflates every p-value for any complex of abundant nuclear proteins. The ranking is the result; the absolute p-values are an upper bound on significance.",
  "CORRECTION_per_bait_2026_09_21": {
    "what_i_got_wrong": "Earlier today I added the pooled complex figures to this entry and used them to withdraw this entry's 'lone core subunit' caution. Running the SAME analysis PER BAIT reverses that for the index fusion. The pooled number is a union over seven baits and is not a statement about MLL-AF4.",
    "in_the_MLL_AF4_column": {
      "complex": "BAF/SWI-SNF",
      "detail": "3 of 17 subunits in the MLL-AF4 column (SMARCB1, SMARCC1, SMARCC2), of which only ONE reaches p<0.05. The 6-subunit BAF signature is the union; MLL-CBP contributes 6 on its own."
    },
    "so_the_original_caution_STANDS_for_the_index_fusion": "The entry's argument was about what the data support for KMT2A::AFF1, and per-bait it is right. My withdrawal was correct about the 960-protein network and wrong about the column that matters. The edge in data/graph/edges/king-cycle48.json marked 'refutes' overstates it and is qualified there.",
    "what_survives_per_bait": "HBO1/KAT7 holds up in the MLL-AF4 column at 4 of 10 subunits (BRPF1, JADE2, JADE3, KAT7) with 3 at p<0.05, and CPSF/3'-end at 4 of 12 with 2 significant. The contaminant control is undiminished per-bait: CCT/TRiC is 8 of 9 in the MLL-AF4 column with 6 significant.",
    "the_per_bait_positive_control": "SEC is 10/16 in MLL-AF4 and 10/16 in MLL-AF9 but 0/16 in MLL-AF1p and MLL-EEN, 1/16 in MLL-CBP and MLL-GAS7, 2/16 in MLL-ENL. Those two baits are exactly the fusions whose C-terminal partners are SEC components. The per-bait method recovers that correctly, which is what licenses reading the other rows per-bait."
  }
}
functionally screened in the source paper
{
  "_added": "king, cycle 48, 2026-09-21, after Q86 flagged that cycle-47 entries understate the record. Verified by me directly from the supplementary file, not from the paper's prose.",
  "screened": true,
  "library_symbol": "SMARCC1",
  "shrnas_for_this_gene": 6,
  "design": "Supplementary Table 6 / MOESM5 is 768 data rows, 128 unique gene symbols, EXACTLY 6 shRNAs each -- counted with openpyxl on 2026-09-21. Negative-selection RNAi screen in MLL-AF9-expressing MOLM-13.",
  "what_this_DOES_establish": "Every one of the 128 conserved MLL-fusion interactors, this protein included, was functionally tested against an MLL fusion. An entry saying 'nothing in the paper validates this prey' is true of BINDING and understates the record.",
  "what_this_does_NOT_establish": "A per-gene result. Scores are presented as heatmaps (Fig. 2c/2d) and no per-gene depletion value is tabulated, so for any individual gene the outcome is measured-not-reported. It is also MLL-AF9 MOLM-13, a myeloid line, not the index fusion and not B-lineage.",
  "absence_class_for_the_per_gene_score": "measured-not-reported"
}
How this could bite us back
  • SMARCC1 is a core subunit of every BAF complex in every cell. It is not a selective target and its loss destabilises the whole remodeller family by proteolysis, so partial inhibition is not obviously safer than complete loss.
  • This graph already carries resistance-swi-snf-bet-dependent-state. Perturbing the BAF core is a documented route into an altered dependency state rather than into cell death.
  • The index-fusion evidence here is p = 0.0707 with 5|4 spectra and a non-zero control. Any intervention argument built on this row is built on a non-significant measurement.
Still open
  1. Are other BAF subunits - SMARCA4, SMARCB1, SMARCE1, ARID1A, ARID1B, ACTL6A, SS18 - in the Skucha 960-protein network? A core-module signature would change the reading of this row entirely; a lone SMARCC1 argues for background.
  2. Which BAF subtype, if any, is recovered? SMARCC1 is in all three, so the row is uninformative about cBAF versus PBAF versus ncBAF - and this graph's own concept entry says a shared core subunit cannot attribute a phenotype to a complex.
  3. Does the MLL-AF4 association survive at a conventional significance threshold in a repeat experiment, given p = 0.0707 here?
Every source behind this entry (3)
  1. E1weak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.paper

    SMARCC1 co-purified with all seven Strep-HA-tagged MLL fusions in isogenic Jurkat cells; the MLL-AF4 (= KMT2A::AFF1) call is p = 0.0707 with 5|4 spectral counts against a 1|0 negative control - above conventional significance and retained by the paper's rank cutoff.

    MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. · Skucha A, Ebner J, Schmoellerl J, Roth M, Eder T, Cesar-Razquin A, Stukalov A, Vittori S, Muhar M, Lu B, Aichinger M, Jude J, Mueller AC, Gyorffy B, Vakoc CR, Valent P, Bennett KL, Zuber J, Superti-Furga G, Grebien F · Nature Communications 2018
    PMID 29777171DOI
    What this evidence cannot show

    SYSTEM: the AP-MS host is JURKAT, a T-ALL line, whereas KMT2A::AFF1 disease is B-lineage infant leukaemia, so a partner that needs a B-cell or infant proteome cannot appear here and a T-lineage partner can appear spuriously. The bait is a Strep-HA-tagged, SINGLE-COPY, doxycycline-INDUCED transgene, not the endogenous fusion. Prey was recovered from bulk nuclear lysate, so co-purification is not evidence of a direct contact. INCLUSION RULE: the paper kept the top 300 interactions per bait by combined p-value rather than applying a p threshold (Methods, verbatim: "The 300 most significant interactions per bait were retained"). Measured by this beat by reading the cached Supplementary Table 5 xlsx directly on 2026-09-21: 545 of the 2,049 per-bait p-values in the table (26.6%) exceed 0.05, to a maximum of 0.175. This graph's own king analysis ana-the-index-fusion-interactome-is-not-distinctive-and-two-earlier-answers-were-artifacts found the MLL-AF4 column reaches deepest into the weak tail of the seven, so an MLL-AF4 p-value is systematically weaker than the same protein's p-value under another bait and should not be read as a weaker interaction. The index-fusion p-value of 0.0707 is ABOVE 0.05 and the negative control is non-zero (1|0). No other BAF subunit is discussed in the paper's body text. Values re-read from the cached xlsx on 2026-09-21.

    Evidence that argues against this (1)
    • IntAct has never curated this dataset (pubid:29777171 returns 0 rows against a working positive control), so no independent curator has re-examined these calls, and the raw data at ProteomeXchange PXD009338 have not been reanalysed here. Nothing in the paper validates this particular prey by an orthogonal assay: of the twelve proteins in this beat, only SETD2 is mentioned anywhere in the paper's body text (counted by regex over the PMC full text, 2026-09-21; SF3A3 appears once, as a named non-selective control). ProteomeXchange/PRIDE 2018
  2. E2established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.paper

    SMARCC1/BAF155 is a core subunit of mammalian SWI/SNF (BAF) complexes, forming with SMARCB1, SMARCE1 and a SMARCD paralogue the core module; the SMARCC1-SMARCE1 binary complex has been crystallised and the core assembly mechanism mapped by co-expression.

    Assembly and interaction of core subunits of BAF complexes and crystal study of the SMARCC1/SMARCE1 binary complex. · Dong C, Zhang R, Xu L, Liu B, Chu X, et al. · Biochem Biophys Res Commun 2022
    PMID 35158202DOI
    What this evidence cannot show

    Recombinant fragments (SMARCC1 447-966 and 862-966) rather than the holocomplex, so the structure is of a sub-assembly. Not a cellular or haematopoietic system. Read from the abstract.

    Evidence that argues against this (1)
    • Core-module composition established in vitro does not predict which BAF subtype - cBAF, PBAF or ncBAF - is present in any given cell, and this graph's own concept-cbaf-pbaf-ncbaf-three-complexes entry records that a shared core subunit cannot attribute a phenotype to a complex. Guo P et al. 2022
  3. E3strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    SMARCC1 levels are controlled by lysine-methylation-dependent proteolysis: methylated SMARCC1/SMARCC2 are degraded via L3MBTL3 and the CRL4-DCAF5 ubiquitin ligase, LSD1 demethylates them to preserve SWI/SNF integrity, and SMARCC1 is the critical target of that axis for embryonic stem cell self-renewal.

    PMID 36335117DOI
    What this evidence cannot show

    Mouse embryonic stem cells and Lsd1/Kdm1a deletion, not a haematopoietic or fusion system. Read from the abstract. Cited here for a specific reason - a subunit whose abundance is set by a degradation switch will vary between cell states, which weakens any inference from a single AP-MS snapshot in one cell line.

    Evidence that argues against this (1)
    • An ESC self-renewal phenotype does not transfer to a leukaemic blast, and LSD1 is itself a therapeutic target in KMT2A-rearranged leukaemia, so the axis may behave differently in the index disease. Dong C et al. 2022
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