FANCF — FA core complex; rank 11 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all

{
  "depmap_common_essential": false,
  "chronos_mean": -0.2975,
  "frac_lines_below_minus_0_5": 0.156
}

{
  "chronos_mean_kmt2a_rearranged": -0.7119,
  "chronos_mean_other_leukaemia": -0.2723,
  "difference": -0.4396,
  "pan_essentiality_all_lines": -0.2975,
  "selectivity_rank": 24,
  "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": 1,
  "kmt2a_records_title_checked": 0,
  "leukaemia_records": 19,
  "aliases_searched": [
    "FANCF"
  ],
  "kmt2a_query": "FANCF[tiab] AND (KMT2A[tiab] OR MLL[tiab])",
  "leukaemia_query": "FANCF[tiab] AND (leukemia[tiab] OR leukaemia[tiab])"
}

{
  "subcellular": "NUCLEUS, the only location UniProt Q9NPI8 annotates, at ECO:0000269 (fetched 2026-09-21). No cytoplasmic pool is annotated - unlike FANCI and BRIP1, which both carry one.",
  "subnuclear": "NOT DIRECTLY MEASURED FOR FANCF. What is published is that FANCF sits in a NUCLEAR FANCA/FANCC/FANCF/FANCG complex whose output - monoubiquitinated FANCD2 - is targeted to nuclear foci [E_q71_loc1]. Attributing the focus to FANCF would be a complex-to-subunit transfer this graph does not permit.",
  "explicit_no": "SAY IT PLAINLY: no subnuclear compartment has been measured for FANCF, in any system. This is UNPUBLISHED, not not-applicable - FANCF is a 374-residue nuclear protein and a subnuclear pool is perfectly possible; nobody has looked. And nothing at all has been measured in a KMT2A-rearranged cell.",
  "how_shown": "complex co-purification plus FANCD2 monoubiquitination immunoblot (PMID 11239454); UniProt Q9NPI8 SUBCELLULAR LOCATION comment, fetched 2026-09-21",
  "systems": "human FA and non-FA fibroblast/lymphoblast lines; 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": "FANCF (Q9NPI8, 374 aa) is a core-complex adaptor and is not FANCD2, FANCI or FANCJ/BRIP1. It is by far the shortest FA protein in this beat, so length discriminates it easily from all of them.",
  "expressed_in": {
    "class": 1,
    "summary": "ubiquitous; no reported cell-type restriction."
  },
  "required_in": {
    "class": 2,
    "claim": "In FANCONI ANAEMIA PATIENTS, the FA pathway is required in HAEMATOPOIETIC STEM AND PROGENITOR CELLS [E_q71_ct1]; FANCF is one of the core-complex genes whose loss defines a complementation group. Pathway-level, not FANCF-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 24 of 17,728 - the best FA score in this graph. Chronos -0.7119 in KMT2A-rearranged against -0.2723 in other leukaemias, difference -0.4396, pan-essentiality -0.2975. Not floor-compressed: the comparator arm sits near -0.27, so there is plenty of dynamic range and the difference is a real one.",
    "but": "Rank 24 on a z-scaled scan is also where brief rule 'a z is not an effect size' bites hardest, and a gene that matters in almost no other leukaemia line earns a large z from a small absolute effect. -0.71 is a modest absolute dependency. And there is no KMT2A literature on FANCF 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-24 placement is a between-arm difference from this project's own scan and is not independent of it. There is no KMT2A literature on FANCF and no FA-pathway state has been scored in a KMT2A-rearranged cell.",
  "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."
}