HCFC2 — menin's other host cell factor, present in the founding paper by gel filtration and never mentioned again

{
  "gene": "HCFC1",
  "graph_entry": "gene-hcfc1",
  "relationship": "host cell factor paralogues; HCFC1 is the one with a defined route into the KMT2A complex via the HCF-binding motif"
}

{
  "method": "molecular sieving (gel filtration co-elution)",
  "interaction_type": "physical association",
  "source_pmid": "15199122",
  "n_source_publications_in_intact": 1,
  "coip_exists": false,
  "binding_region_mapped": false
}

{
  "kmt2a_menin_records_raw": 1,
  "kmt2a_menin_records_excluding_the_source": 0,
  "aliases_searched": [
    "HCFC2",
    "HCF-2"
  ],
  "query": "(HCFC2[tiab] OR \"HCF-2\"[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR menin[tiab])"
}

{
  "chronos_mean_kmt2a_rearranged": 0.1418,
  "chronos_mean_other_leukaemia": 0.0888,
  "difference": 0.053,
  "pan_essentiality_all_lines": 0.126,
  "selectivity_rank": 14972,
  "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."
}

{
  "CONSTITUTIVE": "NUCLEUS AND CYTOPLASM. UniProt Q9Y5Z7 (fetched live 2026-09-21) carries two location values, 'Cytoplasm' and 'Nucleus', both on the same single ECO:0000269, PubMed:10196288 [E_q93_hcfc2_loc1]. That paper is the founding HCF-2 report - Johnson, Mahajan and Wilson, Herpes simplex virus transactivator VP16 discriminates between HCF-1 and a novel family member, HCF-2 - so for once UniProt's coded citation IS about the fact and IS the founding observation. Rule 91 passes here.",
  "AND_UNIPROT_IS_NINETEEN_YEARS_OUT_OF_DATE": "The far better measurement is absent from the record. Gudkova, Dergai, Praz and Herr localised HCF-2 directly and found that UNLIKE HCF-1, WHICH IS EXCLUDED FROM NUCLEOLI, HCF-2 IS NUCLEOLAR - an activity conferred by one and a half C-terminal Fibronectin type 3 repeats and INHIBITED BY THE HCF-1 NUCLEAR LOCALIZATION SIGNAL, in human and mouse cells [E_q93_hcfc2_loc2]. UniProt cites neither this paper nor the nucleolus. So the compartment record for this protein was one paragraph in a 1999 virology paper until this tranche opened the 2019 one.",
  "how_shown": "the 1999 call is from the founding HCF-2 characterisation; the nucleolar call is direct localisation in HEK-293 and mouse cells with domain mapping (the Fn3 repeats) and a dominance test against the HCF-1 NLS",
  "systems": "HEK-293 and mouse cells; herpesvirus-derived cell biology for the 1999 work. NO haematopoietic cell, no leukaemic cell, no KMT2A-rearranged cell",
  "node": "localization-nucleolus-kmt2a-fusion"
}

{
  "measured_in": "HEK-293 for the nucleolar localisation and the overexpression phenotypes, plus mouse cells for the expression survey [E_q93_hcfc2_loc2]; the 1999 founding work is herpesvirus cell biology [E_q93_hcfc2_loc1].",
  "expression": "UniProt Q9Y5Z7 tissue specificity: 'Highly expressed in testis. Detected at lower levels in spleen, thymus, prostate, ovary, small intestine and colon.' SPLEEN AND THYMUS ARE NAMED, so the haematopoietic compartment is at least on the list - the same situation as MAP3K14 in tranche 3 - but at low level and with no cell type resolved. Gudkova et al. additionally show HCF-2 is BROADLY PRESENT in human and mouse cells, which contradicts a reading of the UniProt comment as testis-restricted.",
  "in_leukaemia": "NOTHING. HCF-2's only appearance in this disease is by gel filtration in PMID 15199122, this entry's existing E1, and that is a biochemical co-fractionation and not a cellular measurement of any kind. There is no HCF-2 image, fractionation or compartment measurement in any leukaemic cell."
}

{
  "STATE_IS_PROLIFERATION_VERSUS_DIFFERENTIATION_AND_HCF_2_PUSHES_TOWARDS_DIFFERENTIATION": "Elevated HCF-2 in HEK-293 cells produces phenotypes REMINISCENT OF HCF-1-DEPLETED CELLS - inhibition of cell proliferation and mitotic defects - and inhibits cell-proliferation and metabolism gene-expression programmes while activating differentiation and morphogenesis programmes [E_q93_hcfc2_loc2]. So HCF-2 behaves as a functional ANTAGONIST of HCF-1's proliferative role, not as a redundant paralogue.",
  "why_that_is_pointed_for_this_graph": "HCF-1 is a founding member of the WILD-TYPE KMT2A complex that the fusion cannot bind (gene-hcfc1's central argument), and the defining state of this disease is a DIFFERENTIATION BLOCK. A paralogue of that subunit which raises differentiation programmes and lowers proliferation programmes when its level goes up is, on its face, the more interesting one to measure in a KMT2A-rearranged blast - and nobody has. The direction is not a prediction this entry can make: the experiment was overexpression in HEK-293, which is neither the lineage nor the dose.",
  "bounded": "No HCF-2 cell-state measurement exists in any haematopoietic or leukaemic cell."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"HCFC2\"[tiab] OR \"HCF-2\"[tiab] OR \"HCF2\"[tiab])",
      "querytranslation": "\"HCFC2\"[Title/Abstract] OR \"HCF-2\"[Title/Abstract] OR \"HCF2\"[Title/Abstract]",
      "count": 88,
      "role": "operand control"
    },
    {
      "query": "HCFC2[tiab] AND (nucleolus[tiab] OR nucleolar[tiab])",
      "querytranslation": "\"HCFC2\"[Title/Abstract] AND (\"nucleolus\"[Title/Abstract] OR \"nucleolar\"[Title/Abstract])",
      "count": 0,
      "role": "THE DECISIVE ALIAS MEASUREMENT, half one"
    },
    {
      "query": "\"HCF-2\"[tiab] AND (nucleolus[tiab] OR nucleolar[tiab])",
      "querytranslation": "\"HCF-2\"[Title/Abstract] AND (\"nucleolus\"[Title/Abstract] OR \"nucleolar\"[Title/Abstract])",
      "count": 2,
      "role": "THE DECISIVE ALIAS MEASUREMENT, half two - 0 against 2, and the 2 are the only two subnuclear papers this protein has"
    },
    {
      "query": "(gene clause) AND (subnuclear clause of twelve terms)",
      "count": 2,
      "title_check": "PMID 31049581 (HCF-2 is nucleolar) and PMID 14629117 (C. elegans HCF compartmentalises to nucleus or mitochondria). Both on topic; zero noise.",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (KMT2A/MLL fusion clause of nine terms)",
      "count": 1,
      "title_check": "PMID 15199122 only - the Yokoyama 2004 founding paper, already this entry's E1, with no localisation content.",
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    },
    {
      "query": "(gene clause) AND (localisation clause) AND (fusion clause)",
      "count": 0,
      "bound_not_reproducible_as_stored": "NOT REPRODUCIBLE AS STORED, flagged 2026-09-23. This `query` field records a SUMMARY of the search rather than the search: the clause text it names was never written down, so the string cannot be re-run and this bound could not be included in the cycle-71 audit that re-ran 40 of the corpus's other zero-bounds against the live index (all 40 still returned zero). The clauses have deliberately NOT been reconstructed - guessing them would manufacture a query that was never run, which is worse than an abbreviated one because it would look auditable. This flag does not dispute the count or the absence; it records that this particular bound is not independently checkable."
    }
  ],
  "alias_measurement_verdict": "DECISIVE, and in the direction the brief said not to assume. The CURRENT symbol HCFC2 returns ZERO nucleolar records; the PROTEIN NAME HCF-2 returns TWO, and those two are the entire subnuclear literature for this protein. A beat that had searched only the HGNC symbol would have written 'no subnuclear compartment has been published' - which is exactly what gene-hcfc1 says about the paralogue, from the same missing paper. Tranche 4 measured that the retired-or-alternate-symbol question is a per-gene hypothesis: SKIC8/WDR61/SKI8 was decisive at 2:9:43, CCDC101 versus SGF29 was worthless at 4 versus 44. HCFC2 versus HCF-2 is 0 versus 2 on the decisive fact, which is the most consequential form of the trap - small numbers on both sides, and one of them is the whole answer.",
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "measured-not-curated"
}

{
  "entry": "gene-hcfc1",
  "field": "data.subnuclear_localization and data.localization.subnuclear",
  "currently_says": "NOT MEASURED. No subnuclear compartment has been published for HCFC1 in any system. ... SAY IT PLAINLY: UNPUBLISHED, not not-applicable.",
  "should_say": "A subnuclear STATEMENT about HCFC1 has been published and it is a negative assignment: HCF-1 is EXCLUDED FROM NUCLEOLI, stated as the direct contrast in the paper that establishes HCF-2 is nucleolar. That is not the same as a positive compartment - HCF-1 still has no body or domain assigned to it - but 'no subnuclear compartment has been published in any system' is too strong, and the correct wording is that the only published subnuclear fact about HCF-1 is where it is NOT.",
  "citation": {
    "pmid": "31049581",
    "doi": "10.1093/nar/gkz307",
    "read": "abstract only, fetched from efetch 2026-09-21; the exclusion statement is in the abstract's own words ('Unlike HCF-1, which is excluded from nucleoli, HCF-2 is nucleolar')"
  },
  "note": "Reported, not edited - gene-hcfc1 belongs to the interactome3 beat. This is a narrowing of an absence claim, not a factual error, and it is worth the coordinator's minute because gene-hcfc1's absence claim is load-bearing for that entry's argument that a wild-type-complex subunit has never been compared between fusion and non-fusion cells."
}