FANCI — ID2 module; rank 15 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all

{
  "depmap_common_essential": false,
  "chronos_mean": -0.2994,
  "frac_lines_below_minus_0_5": 0.164
}

{
  "chronos_mean_kmt2a_rearranged": -0.8364,
  "chronos_mean_other_leukaemia": -0.4732,
  "difference": -0.3632,
  "pan_essentiality_all_lines": -0.2994,
  "selectivity_rank": 52,
  "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": 0,
  "kmt2a_records_title_checked": 0,
  "leukaemia_records": 15,
  "aliases_searched": [
    "FANCI",
    "KIAA1794"
  ],
  "kmt2a_query": "(FANCI[tiab] OR KIAA1794[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR \"mixed-lineage leukemia\"[tiab])",
  "leukaemia_query": "(FANCI[tiab] OR KIAA1794[tiab]) AND (leukemia[tiab] OR leukaemia[tiab])"
}

{
  "subcellular": "NUCLEUS AND CYTOPLASM, both at ECO:0000269 in UniProt Q9NVI1 (fetched 2026-09-21). The cytoplasmic pool is a documented asymmetry with its obligate partner FANCD2 (Q9BXW9), which UniProt annotates as Nucleus only - a difference inside a heterodimer that most text treats as a single object.",
  "subnuclear": "CHROMATIN, damage-induced, as the ID complex with FANCD2 [E_q71_loc1]. No resolvable subnuclear BODY is claimed for FANCI; the foci imaged in this pathway were imaged for FANCD2.",
  "explicit_no": "NOT MEASURED IN ANY KMT2A-REARRANGED CELL, and not separable from FANCD2 in any system. UNPUBLISHED rather than not-applicable.",
  "how_shown": "chromatin fractionation and ubiquitination immunoblot after DNA damage (PMID 17412408); UniProt Q9NVI1 SUBCELLULAR LOCATION comment, fetched 2026-09-21",
  "systems": "human non-haematopoietic cell lines with genotoxin challenge; 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": "FANCI (Q9NVI1, 1328 aa) is NOT FANCD2 (Q9BXW9, 1451 aa). They are paralogues that form the obligate ID2 heterodimer and are the most conflated pair in this beat. 123 aa apart, so the stored accession plus length does discriminate them.",
  "expressed_in": {
    "class": 1,
    "summary": "ubiquitous; a cell-cycle-regulated DNA repair effector, 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]. This is a pathway-level requirement pooled across complementation groups, not a FANCI-specific measurement, and FA-I patients are rare.",
    "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 52 of 17,728 in this project's scan: Chronos -0.8364 in KMT2A-rearranged against -0.4732 in other leukaemias, difference -0.3632, pan-essentiality -0.2994. Genuinely in the selective half, with no floor compression - both arms are far from the -2 floor.",
    "but": "A selective DIFFERENCE is not a fusion mechanism. The only requirement documented in a human being is an HSPC requirement in people with no fusion, and this entry's own literature field records that there is no KMT2A literature on FANCI at all."
  },
  "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, loss of the FA pathway IMPOSES rather than maintains an arrested state: unresolved replication stress hyperactivates p53 and drives a late p21-dependent G0/G1 arrest, and p53 knockdown rescues it [E_q71_ct1]. The direction matters - this is a state the cell falls into when the gene is lost, not one the gene sustains.",
    "pmids": [
      "22683204"
    ],
    "system_named_in_the_claim": "human Fanconi anaemia patient HSPCs and FA-like cells"
  },
  "declined_vocabulary": "No 'replication stress' or 'interstrand-crosslink repair' state exists in this graph's 51-term cell vocabulary. Recorded as a vocabulary gap rather than approximated, following the precedent Q69 set. 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": "Every cell-type and cell-state claim here comes from FA patients and FA-like cells carrying no fusion oncoprotein. The rank-52 placement is a between-arm difference from this project's own scan and is not independent of it. No KMT2A-rearranged cell has been scored for an FA-pathway state, and this gene has no KMT2A literature at all.",
  "counter_evidence": {
    "note": "Fork protection failing is a state with several upstream routes, so seeing it in a leukaemic cell does not identify this gene as the cause. SETD1A-catalysed H3K4 methylation at replication forks is what enables FANCD2's histone chaperone activity, and depleting SETD1A - which is not an FA gene - produces the same uncontrolled DNA2-dependent resection of stalled forks and the same loss of RAD51 nucleofilament stability.",
    "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."
}