BRIP1 — downstream effector; rank 22 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all

{
  "depmap_common_essential": false,
  "chronos_mean": -0.3147,
  "frac_lines_below_minus_0_5": 0.166
}

{
  "chronos_mean_kmt2a_rearranged": -0.8174,
  "chronos_mean_other_leukaemia": -0.4717,
  "difference": -0.3457,
  "pan_essentiality_all_lines": -0.3147,
  "selectivity_rank": 63,
  "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."
}

{
  "kmt2a_records_raw": 2,
  "kmt2a_records_title_checked": 0,
  "leukaemia_records": 18,
  "aliases_searched": [
    "BRIP1",
    "BACH1",
    "FANCJ"
  ],
  "kmt2a_query": "(KMT2A[tiab] OR MLL[tiab] OR \"mixed-lineage leukemia\"[tiab]) AND (BRIP1[tiab] OR FANCJ[tiab] OR BACH1[tiab])",
  "leukaemia_query": "(BRIP1[tiab] OR FANCJ[tiab]) AND (leukemia[tiab] OR leukaemia[tiab])"
}

{
  "subcellular": "NUCLEUS AND CYTOPLASM, both at ECO:0000269 in UniProt Q9BX63 (fetched 2026-09-21). The cytoplasmic pool is experimental, not inferred, and every therapeutic argument in this entry is nuclear - so the compartment the drug would also hit is not the compartment the rationale is about.",
  "subnuclear": "INFERRED, NOT MEASURED. BRIP1 binds directly to BRCA1's BRCT repeats and a helicase mutant blocks DSB repair through that interaction [E_q71_loc1], which places it at damage sites by inference. No imaging of BRIP1 foci is cited here and none was found in the searched literature.",
  "explicit_no": "SAY IT PLAINLY: no measured subnuclear compartment for BRIP1 in any system, and nothing at all in a KMT2A-rearranged cell. UNPUBLISHED, not not-applicable.",
  "how_shown": "co-immunoprecipitation and direct binding to BRCA1 BRCT repeats plus a helicase-domain separation-of-function mutant (PMID 11301010); UniProt Q9BX63 SUBCELLULAR LOCATION comment, fetched 2026-09-21",
  "systems": "human breast-cancer and non-haematopoietic cells; no KMT2A-rearranged system",
  "shown_for_fusion_localisation": "no",
  "node": "localization-chromatin-bound-versus-soluble-fraction-kmt2a"
}

{
  "evidence_class_key": "concept-expressed-required-maintains-three-evidence-classes",
  "identifier_note": "NEW IDENTIFIER TRAP, verified live 2026-09-21 and added to data/symbol-collisions.json. gene_exact:BACH1 AND organism_id:9606 AND reviewed:true returns TWO reviewed human records, and the one you probably do not want is FIRST: O14867 BACH1_HUMAN, primary gene BACH1, 'Transcription regulator protein BACH1 (BTB and CNC homolog 1)', 736 aa; then Q9BX63 FANCJ_HUMAN, primary gene BRIP1, synonyms BACH1 and FANCJ, 1249 aa. The whole 2001-2006 DNA-repair literature calls this gene BACH1. Length discriminates cleanly (513 aa apart), gene_primary discriminates, and the protein names do NOT collide - so this is a rule-63 alias trap that the standard defences catch, provided you run them. It is live in this beat: PMID 21362551, cited on gene-mat2a, is about MafK, whose canonical partner is BACH1 the transcription factor.",
  "expressed_in": {
    "class": 1,
    "summary": "ubiquitous; no reported cell-type restriction. A DNA helicase, not a lineage factor."
  },
  "required_in": {
    "class": 2,
    "claim": "In FANCONI ANAEMIA PATIENTS, the FA pathway is required in HAEMATOPOIETIC STEM AND PROGENITOR CELLS [E_q71_ct1]; biallelic BRIP1 loss defines complementation group FA-J. Pathway-level, not BRIP1-specific.",
    "pmids": [
      "22683204"
    ],
    "system_named_in_the_claim": "human Fanconi anaemia patients and FA/FA-like cells, normal haematopoiesis - no fusion present",
    "nodes": [
      "cell-type-hsc-bone-marrow"
    ]
  },
  "the_selectivity_and_what_it_does_not_show": {
    "claim": "Rank 63 of 17,728: Chronos -0.8174 in KMT2A-rearranged against -0.4717 in other leukaemias, difference -0.3457, pan-essentiality -0.3147. Selective half, no floor compression.",
    "but": "Three FA genes - FANCF 24, FANCI 52, BRIP1 63 - cluster in the top 0.4% of the same scan while FANCD2, the pathway's effector, ranks 465. A coherent pathway signal would not usually look like that, and the cleanest alternative explanation is that the KMT2A-rearranged arm (11 lines, none infant-derived) carries a replication-stress phenotype the comparator arm does not - which is a property of those eleven lines, not of the fusion."
  },
  "context": "human FA patients for the requirement; this project's DepMap scan for the selectivity"
}

{
  "evidence_class_key": "concept-expressed-required-maintains-three-evidence-classes",
  "maintains_state": {
    "class": 3,
    "states": [
      "cell-state-quiescence"
    ],
    "claim": "In FANCONI ANAEMIA patient HSPCs, FA-pathway loss IMPOSES a p53/p21-dependent G0/G1 arrest rather than maintaining a state [E_q71_ct1].",
    "pmids": [
      "22683204"
    ],
    "system_named_in_the_claim": "human Fanconi anaemia patient HSPCs and FA-like cells"
  },
  "declined_vocabulary": "No 'replication stress' state exists in this graph's cell vocabulary; recorded as a gap rather than approximated. CLOSED 2026-09-21 by Q73: cell-state-replication-stress-icl-repair now exists and this entry is edged to it with type `regulates` (a mechanism relation - the gene serves the state; it is not a residency claim). The direction this field records is preserved in that node: FA-pathway loss IMPOSES arrest rather than maintaining it, so an edge to cell-state-quiescence would still be wrong.",
  "confidence": "strong",
  "caveats": "All cell-type and cell-state evidence is from fusion-free FA patients. The selectivity rank is a between-arm difference from this project's own scan. This gene has no KMT2A literature.",
  "counter_evidence": {
    "note": "The fork-protection state this gene is invoked for can be produced by a gene that is not in the FA pathway at all: depleting SETD1A, or expressing a chaperone-defective FANCD2 mutant, causes the same DNA2-dependent resection and the same loss of RAD51 nucleofilament stability. So observing fork instability in a KMT2A-rearranged line does not point at BRIP1.",
    "citation": {
      "title": "Histone Methylation by SETD1A Protects Nascent DNA through the Nucleosome Chaperone Activity of FANCD2.",
      "authors": "Higgs MR, Sato K, Reynolds JJ, Begum S, Bayley R, Goula A, Vernet A, Paquin KL, Skalnik DG, Kobayashi W, Takata M, Howlett NG, Kurumizaka H, Kimura H, Stewart GS",
      "year": 2018,
      "venue": "Mol Cell",
      "pmid": "29937342",
      "doi": "10.1016/j.molcel.2018.05.018",
      "type": "paper"
    }
  }
}

{
  "open_targets_dataversion": "26.06",
  "note": "Added by Q71 per brief rule 83; Open Targets dataVersion fetched live 2026-09-21 as year 26 month 06. Scan denominator for this gene: n_all_lines 1208."
}