H2AX - filed as a gene and not as a mark, and the reason that decision changes what the graph can say

{
  "filed_as": "gene",
  "alternative": "histone-marks entry for gamma-H2AX (S139 phosphorylation)",
  "reason": "the entity this beat needs is the protein-coding variant with an accession and a paralogue-collision risk, not the phosphomark; precedent in this graph is gene-h2az1. A gamma-H2AX mark entry would be a separate, complementary node.",
  "length_check_is_weak_here": "143 aa against H2AZ1's 128 aa - the histone family is too short and too similar for length to protect an assertion, so the accession is the handle"
}

[
  "ATM",
  "ATR",
  "DNA-PKcs"
]

{
  "kmt2a_mllt3_screen_positive_rate": "1.17%",
  "runx1_runx1t1": "3.19%",
  "pml_rara": "3.19%",
  "endogenous_damage_in_fusion_positive_vs_negative": "no difference by gamma-H2AX/53BP1 foci, ROS or apoptosis",
  "low_dose_gamma_induction_of_fusions": "none at 50 cGy",
  "pmid": "33803739",
  "title": "Induction of AML Preleukemic Fusion Genes in HSPCs and DNA Damage Response in Preleukemic Fusion Gene Positive Samples.",
  "authors": "Kosik P, Durdik M, Skorvaga M, et al.",
  "venue": "Antioxidants (Basel)",
  "year": 2021,
  "title_provenance": "Title/authors/venue backfilled from PubMed esummary on 2026-09-20 because this citation stored a bare PMID with no title, which made it unscoreable by verify-citations.py. BACKFILLING IS NOT VERIFICATION: it confirms the PMID resolves to a real paper, not that this is the right paper for the claim. That still requires reading."
}

{
  "chronos_mean_kmt2a_rearranged": -0.6698,
  "chronos_mean_other_leukaemia": -0.6357,
  "difference": -0.034,
  "pan_essentiality_all_lines": -0.6324,
  "selectivity_rank": 4928,
  "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."
}

{
  "subcellular": "NUCLEUS AND CHROMOSOME, and for a core histone variant those are the same statement twice. UniProt P16104 fetched 2026-09-21 carries 'Nucleus' on five ECO:0000269 attributions and 'Chromosome' on seven, with NO note, NO subnuclear qualifier and NO isoform- or fragment-scoped comment [E_q89_h2ax_loc1].",
  "THE_TRAP_THIS_FIELD_EXISTS_TO_AVOID": "gamma-H2A.X FOCI ARE NOT H2AX's SUBNUCLEAR LOCALISATION. The phosphorylated form dominates the literature and is a MODIFICATION STATE of a protein that is already everywhere, not a place the protein goes. Rogakou et al. measured exactly this: the protein is distributed through chromatin, and after ionising radiation approximately 1% of H2AX becomes gamma-phosphorylated per gray, corresponding to about 2 x 10^6 base pairs of chromatin per double-strand break - so a focus is a megabase-scale PATCH OF MODIFICATION spreading around a break, in chromatin where unmodified H2AX was already resident [E_q89_h2ax_loc2]. Nothing moves. Writing 'gamma-H2AX forms foci at double-strand breaks' into a localisation field would record a phosphorylation event as a translocation, and this entry refuses to.",
  "the_symbol_layer_of_the_same_trap": "The gene is H2AX (current HGNC), previously H2AFX, and the protein is H2A.X; gamma-H2AX and H2AX pS139 name the modified form. This entry already carries all six strings in its aliases and is filed as a gene rather than as a mark for exactly this reason. A localisation record inherits the whole problem: four of those six strings denote a modification state and only two denote the protein."
}

{
  "in_this_disease": "THE INSTRUMENT'S CELL TYPES, NOT THE PROTEIN'S. This entry already states that in the KMT2A-rearranged literature H2AX is overwhelmingly a readout. The cells in which it has been read are: MLL-rearranged AML lines under chidamide combinations (this entry's E3), AAVS1 MLL-AF4 / AF4-MLL knock-in cells after etoposide and ionising radiation (E4, and that experiment is the index fusion), and umbilical cord blood mononuclear cells from newborns, both preleukaemic-fusion-positive and backtracked pre-diagnostic (E2, E5).",
  "the_protein_itself": "Ubiquitous. UniProt P16104 carries no TISSUE SPECIFICITY comment at all, which for a core histone variant is unremarkable. No haematopoietic-specific expression measurement was sought or found.",
  "grade": "The cell-type record here is a record of where the assay has been run, and this entry says so rather than dressing it as expression data."
}

{
  "DAMAGE_STATE": "The only state that changes anything, and it changes the modification rather than the location: gamma-phosphorylation appears within 1 minute of ionising radiation and is maximal by 10 minutes, at about 1% of H2AX per gray [E_q89_h2ax_loc2].",
  "the_load_bearing_negative_in_this_disease": "MLL-AF4 and AF4-MLL knocked into the AAVS1 locus showed double-strand-break repair kinetics after etoposide and after ionising radiation IDENTICAL to controls (this entry's existing E4) - so in the index fusion, the gamma-H2AX state is not altered by the fusion. That is a fusion-specific negative on the damage state, and it is one of the few dedicated index-fusion experiments this graph holds.",
  "bounded": "No H2AX cell-state result exists beyond the damage axis."
}

{
  "date": "2026-09-21",
  "tool": "NCBI esearch db=pubmed",
  "queries": [
    {
      "query": "H2AX[tiab] AND (\"nuclear distribution\"[tiab] OR \"chromatin distribution\"[tiab] OR subnuclear[tiab] OR nucleolar[tiab])",
      "querytranslation": "\"H2AX\"[Title/Abstract] AND (\"nuclear distribution\"[Title/Abstract] OR \"chromatin distribution\"[Title/Abstract] OR \"subnuclear\"[Title/Abstract] OR \"nucleolar\"[Title/Abstract])",
      "count": 43,
      "reading": "Forty-three records, and titles indicate they are overwhelmingly about gamma-H2AX FOCI in relation to other compartments (nucleolar DNA damage, UBF1 regions) rather than about unmodified H2AX's distribution. The literature is about the mark, as expected."
    },
    {
      "query": "(H2AX[tiab] OR \"gamma-H2AX\"[tiab]) AND menin[tiab]",
      "querytranslation": "(\"H2AX\"[Title/Abstract] OR \"gamma-H2AX\"[Title/Abstract]) AND \"menin\"[Title/Abstract]",
      "count": 0,
      "reading": "ZERO. Recorded because this graph carries a menin-gammaH2A.X-SETD2-H3K36me3-LEDGF chain reached through eighteen entries, and NO PAPER NAMES MENIN AND H2AX TOGETHER IN A TITLE OR ABSTRACT. The chain is assembled from separate links in this graph, not lifted from a paper that draws it.",
      "operand_controls": "menin[tiab] alone returns 1,264 (measured 2026-09-21 and recorded in data/symbol-collisions.json); H2AX[tiab] alone is in the tens of thousands. Two large sets with an empty intersection is a claim that needs its own evidence - here it is a real zero, and the query shape is one tag per term with the querytranslation read back, so rules 67, 94 and 95 are all satisfied."
    }
  ],
  "absence_class": "never-measured",
  "caveat_rule_80": "Both zeros are bounded by TITLES AND ABSTRACTS. A gamma-H2AX measurement under a menin inhibitor could sit in a supporting figure of any menin-inhibitor paper and would be invisible to this query - which is exactly the failure rule 80 documents for the SET-NUP214 H3K79 case."
}