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

[
  "GCN5L2",
  "hGCN5"
]

{
  "depmap_common_essential": null,
  "note": "Not queried here. The preprint reports SAGA as a selective chromatin dependency from genome-scale data, but this graph's paralogue analysis requires a per-gene test before a module-level claim is accepted."
}

{
  "chronos_mean_kmt2a_rearranged": -0.3499,
  "chronos_mean_other_leukaemia": -0.2932,
  "difference": -0.0567,
  "pan_essentiality_all_lines": -0.2344,
  "selectivity_rank": 2983,
  "rank_denominator": 17728,
  "provenance": "Joined 2026-09-21 from analyses/depmap-kmt2a-selective-scan-full (generated 2026-09-19T10:12:06Z), the project's own genome-wide scan over 11 KMT2A-rearranged and 43 other leukaemia DepMap lines. NOT re-fetched and NOT independent of that scan: every caveat it carries applies here, including that the KMT2A-rearranged arm is a small number of lines drawn from nine individuals, that the rank denominator is 17,728 genes, and that a difference is not a dependency. Added because only 26 of 308 gene entries carried this number, which made any KMT2A-selectivity question answerable for 8% of the corpus.",
  "how_to_read": "A negative difference means MORE required in KMT2A-rearranged lines than in other leukaemia lines. A rank near 17,728 is ANTI-selective. Neither is evidence of a fusion-driven dependency on its own: check pan_essentiality_all_lines before calling anything selective, and note that a paralogue-redundant gene can score near zero for reasons that have nothing to do with this disease - see ana-the-paralogue-redundancy-excuse-is-not-tested-and-my-proxy-decided-the-answer."
}

{
  "CONSTITUTIVE": "NUCLEUS, AND FOR ONCE THE RECORD IS GOOD. UniProt Q92830 (fetched live 2026-09-21) carries three location values with FOUR distinct experimental citations: 'Nucleus' (ECO:0000269 PubMed:11564863, 25593309, 27796307, 29211711), 'Chromosome' (ECO:0000269 PubMed:29211711) and 'Cytoplasm, cytoskeleton, microtubule organizing center, CENTROSOME' (ECO:0000269 PubMed:27796307), with the note 'Mainly localizes to the nucleus. Localizes to sites of DNA damage. Also localizes to centrosomes in late G1 and around the G1/S transition, coinciding with the onset of centriole formation' [E_q93_kat2a_loc1]. Tissue specificity: 'Expressed in all tissues tested'.",
  "THE_CONTRAST_WITH_SGF29_IS_THE_FINDING": "Tranche 4 established that SGF29, another SAGA subunit written in this graph, has NO human experimental localisation evidence at all - its single 'Nucleus' value is ECO:0000250 propagated from SGF29_RAT, whose own call rests on one hepatocellular-carcinoma paper. KAT2A, the catalytic subunit of the same complex, has four independent human ECO:0000269 citations, a cell-cycle-scoped second compartment and a DNA-damage-scoped third. SO THE QUALITY OF A LOCALISATION RECORD IS A PROPERTY OF HOW MUCH ATTENTION A SUBUNIT HAS HAD, NOT OF THE COMPLEX IT SITS IN, and a beat that generalises 'SAGA subunits are poorly localised' from either entry would be wrong.",
  "AND_ONE_OF_THOSE_FOUR_CITATIONS_IS_THE_INVERTING_CASE_BRIEF_RULE_91_ASKS_ABOUT": "PubMed:25593309 is the ZMYND8/NuRD bromodomain DNA-damage screen that brief rule 91 names as one of the papers UniProt MISCITES for KMT2A. For KAT2A it is on topic: the screen's own headline is that MORE THAN ONE-THIRD OF ALL HUMAN BROMODOMAIN PROTEINS CHANGE LOCALIZATION IN RESPONSE TO DNA DAMAGE, and KAT2A has a bromodomain, so a bromodomain-wide relocalisation screen is a genuine localisation measurement for this protein [E_q93_kat2a_loc2]. The same citation is an error on one entry and correct on another. That is the cleanest available demonstration that rule 91 has to be checked per gene rather than per paper.",
  "how_shown": "STAGA complex purification and characterisation (PMID 11564863); a bromodomain-wide microscopy screen of DNA-damage relocalisation (PMID 25593309); acetylome proteomics plus centrosome imaging through the cell cycle (PMID 27796307); nuclear alpha-KGDH localisation with KAT2A promoter binding and crystallography (PMID 29211711)",
  "systems": "human cell lines throughout; NONE haematopoietic, none leukaemic, none fusion-bearing",
  "node": "localization-wdr5-kmt2a-centrosome-and-midbody"
}

{
  "expressed_in": "UniProt Q92830: 'Expressed in all tissues tested' - ubiquitous, no lineage information.",
  "measured_in": "human cell lines for all four localisation citations; none haematopoietic.",
  "in_this_disease": "The cell-type record is this entry's existing content and it is unusually good for a localisation beat to inherit: the SAGA DUB module result (this entry's E2, PMID 42418681) comes from a genome-wide CRISPR screen in a KMT2A-REARRANGED B-CELL ALL LINE - LYMPHOID, the right lineage - and the acetyltransferase-module result (E1, PMID 42523331) includes an ISOGENIC KMT2A-REARRANGED MODEL plus primary AML patient samples. Neither contains a KAT2A localisation measurement.",
  "the_gap_stated_precisely": "KAT2A has four human compartment measurements and none in a blood cell; it has two recent results in KMT2A-rearranged cells and no compartment in either. The two literatures do not touch."
}

{
  "CELL_CYCLE_IS_THE_DOCUMENTED_STATE_AND_IT_IS_POSITIONAL": "KAT2A's centrosomal pool is not constitutive - it appears in LATE G1 AND AROUND THE G1/S TRANSITION, coinciding with the onset of centriole formation [E_q93_kat2a_loc4]. So a bulk immunofluorescence in an asynchronous population averages a nuclear majority with a phase-restricted centrosomal minority, which is the same measurement problem this graph records in cell-state-unsynchronisable-cell-cycle.",
  "DNA_DAMAGE_IS_THE_SECOND_STATE": "KAT2A is one of the bromodomain proteins whose localisation CHANGES in response to DNA damage, in a screen where more than a third of the family did so [E_q93_kat2a_loc2]. Induced relocalisation, not a resting address.",
  "and_the_state_the_2026_preprint_reports_is_a_CONDENSATE_state_in_the_index_fusions_own_machinery": "KAT2A/KAT2B license acetylation of H3K9 and of SEC components INCLUDING ENL, AFF1 AND AFF3; degrading them with a cereblon-recruiting PROTAC DISPLACES ENL FROM TARGET LOCI AND DISSOLVES ENL-ANCHORED TRANSCRIPTIONAL CONDENSATES (this entry's existing E1, PMID 42523331). AFF1 is the index fusion's partner. That is a localisation readout in the fusion's own machinery and it is the only one in this tranche.",
  "bounded": "No KAT2A compartment measurement of any kind exists in a haematopoietic or leukaemic cell, so the condensate result above is about ENL's position and not about KAT2A's."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"KAT2A\"[tiab] OR \"GCN5\"[tiab] OR \"GCN5L2\"[tiab])",
      "querytranslation": "\"KAT2A\"[Title/Abstract] OR \"GCN5\"[Title/Abstract] OR \"GCN5L2\"[Title/Abstract]",
      "count": 1874,
      "role": "operand control"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 36,
      "title_check": "screened; no KAT2A nuclear-body, speckle or PML paper identified. The nucleolar hits are dominated by snoRNA/SNHG contamination, the same mechanism that gave 0 of 4 on JAK1 and 0 of 7 on IGF2BP2 in this tranche.",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (nine-term KMT2A/MLL fusion clause)",
      "count": 7,
      "title_check": "the three 2026 records are this entry's E1 and E2 plus a CRBN molecular-glue paper (PMID 42424456); the older four are the off-beat set this entry's existing E4 already enumerates.",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (localisation clause) AND (fusion clause)",
      "count": 0,
      "role": "the load-bearing zero",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "KAT2A[tiab] AND centrosome[tiab]",
      "querytranslation": "\"KAT2A\"[Title/Abstract] AND \"centrosome\"[Title/Abstract]",
      "count": 3,
      "role": "corroborating the non-nuclear pool"
    }
  ],
  "ALIASES_NOT_SEARCHED_GAP_NOW_CLOSED_AND_THE_ANSWER_IS_NOTHING": "This entry's data.aliases_not_searched named GCN5L2 and hGCN5 as unrun. Both were run 2026-09-21: GCN5L2[tiab] returns 19 records, hGCN5[tiab] returns 32, and GCN5L2[tiab] AND (MLL[tiab] OR KMT2A[tiab]) and hGCN5[tiab] AND the same clause BOTH RETURN ZERO. So the retired and informal symbols add no fusion-context literature whatsoever, and this entry's existing conclusion - that the route into this disease is through the COMPLEX NAME and not through any spelling of the gene symbol - is strengthened rather than qualified. Recorded as a measurement because tranche 4 established the retired-symbol question is a per-gene hypothesis: decisive for SKIC8 (2:9:43), worthless for SGF29/CCDC101 (44 versus 4), decisive-for-provenance-only for CTR9/p150TSP in this tranche, and WORTHLESS here.",
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "never-measured"
}

{
  "GCN5L2": 19,
  "hGCN5": 32,
  "GCN5L2_AND_fusion": 0,
  "hGCN5_AND_fusion": 0,
  "verdict": "no additional fusion-context literature from either; supersedes data.aliases_not_searched"
}