FAAP100 — FA core complex; rank 36 of 8,269 for KMT2A-selective dependency, and no KMT2A literature at all

{
  "depmap_common_essential": false,
  "chronos_mean": -0.3318,
  "frac_lines_below_minus_0_5": 0.143
}

{
  "chronos_mean_kmt2a_rearranged": -0.6619,
  "chronos_mean_other_leukaemia": -0.3894,
  "difference": -0.2725,
  "pan_essentiality_all_lines": -0.3318,
  "selectivity_rank": 125,
  "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": 2,
  "aliases_searched": [
    "FAAP100",
    "C17orf70"
  ],
  "kmt2a_query": "(FAAP100[tiab] OR C17orf70[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR \"mixed-lineage leukemia\"[tiab])",
  "leukaemia_query": "(FAAP100[tiab] OR C17orf70[tiab]) AND (leukemia[tiab] OR leukaemia[tiab])"
}

{
  "subcellular": "NUCLEUS, AND NOTHING ELSE - the shortest coded record in this tranche. UniProt Q0VG06 fetched 2026-09-21 carries a single location, 'Nucleus', at ECO:0000269 on two references: the 2007 EMBO J paper that identified FAAP100 and the 2025 J Clin Invest paper reporting the first patients [E_q77_loc1]. There is no cytoplasmic annotation, no note and no isoform comment. Unlike FANCG in the same complex, whose two compartments rest on one unrelated paper, FAAP100's single compartment rests on the two papers that define the protein - so the record is thin but it is pointing at the right places.",
  "subnuclear": "NOT MEASURED, AND FOR FAAP100 THE RECORD IS SHORTER THAN FOR ANY OTHER NUCLEAR PROTEIN IN THIS TRANCHE: UniProt Q0VG06 annotates ONE location, 'Nucleus', at ECO:0000269 on two references, with NO note, no second compartment and no isoform-scoped statement [E_q77_loc1]. No subnuclear measurement of FAAP100 exists in any system - no focus, body, matrix or chromatin-fraction result. The pathway's subnuclear currency is monoubiquitinated FANCD2/FANCI in nuclear foci, and FAAP100 scaffolds the FANCB-FANCL module that INSTALLS that mark [E_q77_loc2], so the protein sits one step upstream of the only compartment anyone images in this pathway. UNPUBLISHED rather than not-applicable, and the reagents now exist: the 2025 patient study generated FAAP100-null material and showed the core complex is disrupted without it [E_q77_loc3].",
  "how_shown": "identification and characterisation of FAAP100 as an essential component of the FA core complex, with FANCD2 monoubiquitination as the functional readout [E_q77_loc2]; patient-derived genetic inactivation with core-complex integrity and monoubiquitin-ligase readouts [E_q77_loc3]",
  "systems": "human cells and human patient-derived material. NO haematopoietic localisation experiment, no primary blast, nothing KMT2A-rearranged.",
  "shown_for_fusion_localisation": "NO - nobody has looked in any fusion, and for this gene the absence is absolute. This entry already records a bounded literature search returning ZERO records for FAAP100 or C17orf70 against KMT2A, MLL or 'mixed-lineage leukemia', and only two records against leukaemia at all. There is no localisation measurement because there is no literature.",
  "node": "localization-chromatin-bound-versus-soluble-fraction-kmt2a",
  "the_experiment_that_is_now_cheap": "The 2025 J Clin Invest study generated the first FAAP100 patient material and showed that genetic inactivation disrupts the monoubiquitin ligase core complex. That means a FAAP100-null and a corrected human line now exist. Asking whether FANCD2 foci form, and whether the core complex is chromatin-associated, in a KMT2A-rearranged background is a fractionation and an immunofluorescence away - and it would test the mechanism behind this entry's rank-125-of-17,728 selectivity signal directly rather than by inference."
}

{
  "evidence_class_key": "concept-expressed-required-maintains-three-evidence-classes",
  "identifier_note": "FAAP100 is Q0VG06, 881 aa, entry name FP100_HUMAN, alias C17orf70. data/symbol-collisions.json was grepped for FAAP100 and C17orf70 before the first query and has NO row for either; none is proposed. The retrieval hazard is the open-reading-frame alias: material from before the protein was named is indexed under C17orf70, which this entry's literature block records as having been searched.",
  "expressed_in": {
    "class": 1,
    "summary": "ubiquitous; not pan-essential (mean Chronos -0.3318, 14.3% of lines below -0.5, per this entry's own [E4]) - a deeper baseline than FANCG's but still not common-essential."
  },
  "required_in": {
    "class": 2,
    "claim": "FAAP100 IS REQUIRED FOR THE FA PATHWAY ITSELF, AND THE HUMAN CELL-TYPE CONSEQUENCE IS THE FA PHENOTYPE. FAAP100 is essential for activation of the Fanconi-anaemia-associated DNA damage response pathway [E_q77_loc2], and genetic inactivation of FAAP100 CAUSES FANCONI ANAEMIA in patients through disruption of the monoubiquitin ligase core complex [E_q77_loc3] - which establishes FAAP100 as a bona fide FA gene rather than an accessory factor. The haematopoietic cell-type consequence is then the FA one: a profound human HSPC defect present before clinical marrow failure, driven by hyperactivated p53 and a late p21-dependent G0/G1 arrest that p53 knockdown rescues [E_q77_ct1].",
    "pmids": [
      "17396147",
      "40232843",
      "22683204"
    ],
    "system_named_in_the_claim": "human cells for the pathway requirement, human patients for the disease causation, and human FA patient HSPCs plus FA-like models for the haematopoietic phenotype - no fusion anywhere",
    "nodes": [
      "cell-type-hsc-bone-marrow"
    ],
    "the_pathway_versus_the_subunit": "The HSPC phenotype is a PATHWAY result across complementation groups and is not FAAP100-specific; what IS FAAP100-specific is that its loss causes FA, which makes the pathway attribution legitimate for this subunit in a way it would not be for an accessory factor. That distinction is why the 2025 patient paper matters here and is worth more than its recency."
  },
  "context": "human patients and human cells throughout; no fusion, no leukaemia"
}

{
  "evidence_class_key": "concept-expressed-required-maintains-three-evidence-classes",
  "maintains_state": {
    "class": 3,
    "states": [
      "cell-state-replication-stress-icl-repair",
      "cell-state-quiescence"
    ],
    "claim": "THE STATE IS THE SAME AS FOR FANCG AND FOR THE PATHWAY: losing it arrests progenitors rather than killing them, through hyperactivated p53 and a late p21-dependent G0/G1 block that p53 knockdown reverses [E_q77_ct1]. What FAAP100 adds is that this is now anchored in a human genetic disease caused by loss of THIS subunit [E_q77_loc3], rather than extrapolated from other complementation groups.",
    "pmids": [
      "22683204",
      "40232843"
    ],
    "system_named_in_the_claim": "human FA patient HSPCs and FA-like models for the state; human FAAP100 patients for the causal genetics - no fusion"
  },
  "the_same_caution_as_fancg_and_it_is_load_bearing": "A p53/p21-dependent G0/G1 arrest is scored by a CRISPR proliferation screen exactly as a dependency is. This entry exists because FAAP100 ranks 125 of 17,728 for KMT2A-selective dependency, and the mechanism most likely to produce that signal - FA pathway loss causing p53-dependent arrest - is a mechanism whose magnitude should depend on the TP53 status of the lines. Splitting the DepMap arms on TP53 status is free and has not been done for either FA entry in this graph. If the effect vanishes in TP53-mutant lines, the whole FA/BRCA signal in this scan is a p53 signal.",
  "confidence": "moderate",
  "caveats": "The HSPC state evidence is pathway-level across FA complementation groups and predates the identification of FAAP100 patients by thirteen years, so it is applied to this subunit by inference from its being a bona fide FA gene. No fusion, no leukaemia, and no haematopoietic experiment specific to FAAP100 exists at all. This entry's own [E7] remains the standing objection: FA patients with no pathway develop KMT2A-rearranged leukaemia.",
  "counter_evidence": [
    {
      "note": "This entry already records that the obligate FA core subunits do NOT move together in the DepMap data, which is hard to reconcile with a canonical pathway dependency - and it is equally hard to reconcile with importing a pathway-level cell-state result onto one subunit, which is what this block does. The honest position is that FAAP100 is a genuine FA gene whose loss causes the disease, that the FA HSPC state is well characterised at pathway level, and that the DepMap behaviour of the subunits is inconsistent with both being the explanation for the scan hit. One of the three is wrong and nothing in this beat resolves which.",
      "citation": {
        "title": "Bone marrow failure in Fanconi anemia is triggered by an exacerbated p53/p21 DNA damage response that impairs hematopoietic stem and progenitor cells.",
        "authors": "Ceccaldi R, Parmar K, Mouly E, Delord M, Kim JM, Regairaz M, Pla M, Vasquez N, Zhang QS, Pondarre C, Peffault de Latour R, Gluckman E, Cavazzana-Calvo M, Leblanc T, Larghero J, Grompe M, Socié G, D'Andrea AD, Soulier J",
        "year": 2012,
        "venue": "Cell Stem Cell",
        "pmid": "22683204",
        "doi": "10.1016/j.stem.2012.05.013",
        "type": "paper"
      }
    }
  ]
}