EP400 - the ATPase that swaps H2A.Z in; its complex is required by MLL leukaemia stem cells, and in DepMap it is one of the three genes LEAST required in KMT2A-rearranged lines

[
  "EPC1",
  "EPC2",
  "KAT5/Tip60"
]

{
  "index_mean": -0.9007,
  "other_leukaemia_mean": -1.0217,
  "difference": 0.1211,
  "pan_essentiality": -0.9321,
  "myeloid_difference": 0.1541,
  "lymphoid_difference": 0.0522,
  "n_index": 11
}

{
  "chronos_mean_kmt2a_rearranged": -0.9007,
  "chronos_mean_other_leukaemia": -1.0217,
  "difference": 0.1211,
  "pan_essentiality_all_lines": -0.9321,
  "selectivity_rank": 17211,
  "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 IT IS THE WEAKEST EVIDENCE CLASS IN THIS ENTIRE TRANCHE. UniProt Q96L91 (fetched live 2026-09-21) carries exactly ONE SUBCELLULAR LOCATION value, 'Nucleus', supported by ECO:0000255 PROSITE-ProRule PRU00549 - A SEQUENCE-MOTIF RULE. Not ECO:0000269 (a curator read an experiment), not ECO:0000250 (propagated from an orthologue), not even ECO:0000305 (curator inference from other data). A ProRule-derived compartment is generated by the presence of a domain, so the statement 'EP400 is nuclear' on this record is a restatement of 'EP400 contains a domain that nuclear proteins have' [E_q93_ep400_loc1].",
  "RANK_THIS_AGAINST_THE_OTHER_WEAK_CASES_THIS_BEAT_HAS_FOUND": "The beat has now catalogued a full ladder of compartment-annotation quality on genes in this graph: FOUR human experimental citations (KAT2A); coded but the citation is a crystal structure (NFKB1 p50); coded and about the fact (CHUK, HCFC2); propagated from a rodent with one paper behind it (SGF29, CTR9, CSNK2A2); a bare unsourced value with an empty evidence list (MAP3K14, JAK1); and HERE, A RULE-GENERATED VALUE. This graph already holds localization-meis1-nucleus-is-a-sequence-prediction-and-one-isoform-is-cytoplasmic for exactly this pathology, and EP400 is the second instance - on a 3,159-residue ATPase that nobody doubts is nuclear, which is precisely why nobody has ever checked.",
  "what_is_solid_instead": "The function is a nuclear function and no source disputes the compartment. EP400 is the ATPase of the p400/TIP60 (NuA4) complex and one of the two remodellers that deposit H2A.Z-H2B delivered by YL1/VPS72 (this entry's existing E1); H2A.Z deposition happens on chromatin, so the compartment is not in question. What is recorded here is that for one of the largest chromatin ATPases in the human proteome, the database's compartment is a motif prediction and the literature bound is empty.",
  "how_shown": "nothing. ECO:0000255 PROSITE-ProRule PRU00549 only",
  "systems": "none for the compartment. The functional work is in human cell lines and murine MLL-AF9 leukaemia via the EPC1/EPC2 subunits (this entry's existing E2)",
  "node": "localization-chromatin-bound-versus-soluble-fraction-kmt2a"
}

{
  "expressed_in": "UniProt Q96L91 tissue specificity: 'Ubiquitously expressed' - no lineage information.",
  "measured_in": "nothing for the compartment. HeLa and cell-free systems for the VPS72/H2A.Z nuclear-reassembly work; 77 human breast-cancer patients for the H4K12ac ChIP work; murine MLL-AF9 AML cells for this entry's existing EPC1/EPC2 result.",
  "in_this_disease": "This entry's existing content is the cell-type record and it is genuinely contradictory, which is the entry's whole point: EPC1 or EPC2 knockdown induces apoptosis of murine MLL-AF9 AML cells and abolishes leukaemia stem cell potential WHILE SPARING NORMAL HSPCs, and yet in DepMap EP400 itself is among the genes LEAST required in KMT2A-rearranged lines. Neither arm involves a localisation measurement, and the system for the positive arm is murine and MYELOID rather than infant B-lineage.",
  "the_gap": "No EP400 image, fractionation or compartment measurement exists in any cell of any kind."
}

{
  "MITOTIC_EXIT_IS_THE_ONE_DOCUMENTED_STATE_FOR_THE_PATHWAY": "H2A.Z deposition by VPS72/YL1 is required for nuclear reassembly after mitosis: siRNA knockdown of VPS72 extends telophase in live HeLa cells, and depleting VPS72 or H2A.Z in vitro yields malformed and non-functional nuclei [E_q93_ep400_loc3]. So the EP400 pathway has a phase at which it is needed - telophase into early interphase - and this entry's existing framing of EP400 as a histone-variant exchange motor at gene switches does not capture that.",
  "and_a_second_state_claim_that_is_weaker": "The heterochromatin-back-up-skeleton proposal frames TIP60/P400/H4K12ac as a fallback for the SUV39H1/H3K9me3/HP1 skeleton when that is lost in carcinogenesis, with TIP60 and P400 mRNA overexpression associated with tumour aggressiveness [E_q93_ep400_loc2]. That is a disease-state association in breast cancer, in a low-impact venue, and is recorded as adjacent rather than as support.",
  "bounded": "No EP400 cell-state or localisation measurement exists in any leukaemic cell, and nothing under a menin inhibitor."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"EP400\"[tiab] OR \"p400\"[tiab] OR \"TNRC12\"[tiab] OR \"CAGH32\"[tiab])",
      "querytranslation": "\"EP400\"[Title/Abstract] OR \"p400\"[Title/Abstract] OR \"TNRC12\"[Title/Abstract] OR \"CAGH32\"[Title/Abstract]",
      "count": 501,
      "role": "operand control - inflated by 'p400' as an apparent-mass label, the same trap as p50 and p105 on NFKB1 in this tranche"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 9,
      "title_check": "0 are EP400 compartment studies. The two adjacent ones cited here are PMID 33099470 (TIP60/P400/H4K12ac as a heterochromatin back-up skeleton in breast cancer) and PMID 32708675 (VPS72/YL1-mediated H2A.Z deposition required for nuclear reassembly after mitosis). The rest are H2A.Z reviews, a JAZF1 complex-membership paper, DNA-repair chromatin dynamics, BS69/senescence, PHF5A in spermatogenesis and the yeast Swr1p paper.",
      "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": 2,
      "title_check": "PMIDs 26625313 and 24166297; neither is a localisation measurement.",
      "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,
      "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": "EP400[tiab] AND (nuclear[tiab] OR nucleus[tiab] OR chromatin[tiab])",
      "querytranslation": "\"EP400\"[Title/Abstract] AND (\"nuclear\"[Title/Abstract] OR \"nucleus\"[Title/Abstract] OR \"chromatin\"[Title/Abstract])",
      "count": 53,
      "role": "symbol-only control, unscreened; 'chromatin' matches the complex's function in nearly every EP400 paper so this is a literature size and not a localisation count"
    }
  ],
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80). For a 3,159-residue protein with no compartment paper, a figure-level localisation almost certainly exists somewhere in the p400/TIP60 literature; what is established is that no paper is ABOUT it and that UniProt found none to cite.",
  "absence_class": "measured-not-reported"
}