NFKB1 (p105/p50) — the only menin-NF-kB subunit with a co-immunoprecipitation, and the arm the MLL leukaemia data points at

{
  "methods": [
    "anti-bait co-immunoprecipitation",
    "GST pull-down"
  ],
  "source_pmid": "11526476",
  "n_source_publications_in_intact": 1,
  "directional_effect_on_p50_shown": false
}

{
  "kmt2a_records_raw": 4,
  "kmt2a_records_title_checked": 0,
  "aliases_searched": [
    "NFKB1",
    "NF-kappaB1",
    "p105",
    "p50"
  ],
  "kmt2a_query": "(NFKB1[tiab] OR \"NF-kappaB1\"[tiab] OR p105[tiab] OR p50[tiab]) AND (KMT2A[tiab] OR MLL[tiab] OR \"mixed-lineage leukemia\"[tiab])"
}

{
  "chronos_mean_kmt2a_rearranged": 0.0056,
  "chronos_mean_other_leukaemia": 0.0363,
  "difference": -0.0307,
  "pan_essentiality_all_lines": 0.0249,
  "selectivity_rank": 5295,
  "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": "MOLECULE-SCOPED, AND THAT IS THE WHOLE POINT. UniProt P19838 (fetched live 2026-09-21) does not carry one location comment; it carries TWO, each scoped to a named processing product, exactly as UniProt does for KMT2A's taspase1 fragments [E_q93_nfkb1_loc1]: (1) molecule 'Nuclear factor NF-kappa-B p105 subunit' -> CYTOPLASM, ECO:0000269 PubMed:1423592; (2) molecule 'Nuclear factor NF-kappa-B p50 subunit' -> NUCLEUS and CYTOPLASM, both ECO:0000269 PubMed:9865693, with the note that association with NFKBIA promotes retention in the cytoplasm in an inactive form and that it translocates into the nucleus following NFKBIA degradation. The feature table carries a nuclear localization signal at residues 360-365.",
  "WHY_THE_MOLECULE_SCOPING_MATTERS_HERE_MORE_THAN_ANYWHERE": "This is the second protein in this graph, after KMT2A itself, whose UniProt compartment record is FRAGMENT-RESOLVED because the protein is proteolytically processed into species with different addresses. Brief rule 91 records that filtering Q03164 on ECO:0000269 keeps the least useful line and discards both KMT2A fragment comments. For NFKB1 the same filter keeps BOTH lines, because both are coded - so NFKB1 is the worked positive example of the thing rule 91 says usually goes wrong, and it is the better template. The precursor is cytoplasmic; the processed DNA-binding subunit shuttles.",
  "AND_THE_P50_CITATION_IS_A_CLEAN_RULE_91_INSTANCE": "PubMed:9865693 is Jacobs and Harrison, 'Structure of an IkappaBalpha/NF-kappaB complex', Cell 1998 - a 2.7 angstrom X-RAY CRYSTAL STRUCTURE of the IkappaBalpha ankyrin-repeat domain bound to a partially truncated p50/p65 heterodimer [E_q93_nfkb1_loc2]. A CRYSTAL STRUCTURE CANNOT LOCALISE A PROTEIN IN A CELL. What the structure shows is a mechanism for cytoplasmic retention - the first two ankyrin repeats cover an alpha-helically ordered segment containing the p65 NLS - and that is a structural explanation OF a localisation, not a measurement of one. The founding cell-biological observations of p50 nuclear translocation are not cited on this field at all.",
  "how_shown": "for p105, cotransfection and cofractionation showing p105 retains c-Rel or p65 in the cytoplasm and inhibits their DNA binding (PMID 1423592); for p50, an X-ray structure of an IkappaBalpha/NF-kappaB complex (PMID 9865693), which is not a localisation assay",
  "systems": "COS cells and various cell lines for the 1992 p105 work; crystallography for the 1998 structure. No haematopoietic cell, no leukaemic cell, no KMT2A-rearranged cell",
  "node": "localization-chromatin-bound-versus-soluble-fraction-kmt2a"
}

{
  "expressed_in": "Ubiquitous; NFKB1 is a component of the canonical NF-kB machinery in essentially every nucleated cell, asserted here as background rather than measured in this beat.",
  "measured_in": "COS cells and assorted cell lines (1992); no cells at all for the p50 citation, which is crystallography.",
  "in_this_disease": "The route in is p105 PROCESSING rather than p50 abundance, and it is this entry's existing content: the signalling that generates p50 is unusually active in MLL-rearranged leukaemia cells, and nobody has checked whether removing menin pharmacologically changes the menin-p50 contact. The cell type in which that has been observed is MLL-rearranged leukaemia lines and murine MLL-AF9 - MYELOID, per gene-rela's system note - not infant B-lineage KMT2A::AFF1.",
  "what_is_missing_is_a_fraction_not_a_cell": "For a protein whose activation IS its translocation, the informative cell-type measurement is the nuclear-to-cytoplasmic p50 ratio in a KMT2A-rearranged blast, resolved for p105 versus p50. No paper reports it."
}

{
  "state": "IkappaB-DEPENDENT LATENCY VERSUS ACTIVATION, and it is a compartment state by definition. p50 is held in the cytoplasm in an inactive form by association with NFKBIA and translocates into the nucleus following NFKBIA degradation [E_q93_nfkb1_loc1]; the structural basis is that the first two ankyrin repeats of IkappaBalpha cover the segment containing the NLS [E_q93_nfkb1_loc2]. Separately, the PRECURSOR itself is an inhibitor: p105 associates with c-Rel or p65 in the cytoplasm, retains them there and blocks their DNA binding, requiring both the Rel-homology dimerisation surface and a second contact through its IkappaB-related C-terminus [E_q93_nfkb1_loc4].",
  "so_there_are_THREE_states_not_two": "unprocessed p105 sequestering partners; processed p50 held by IkappaB; and processed p50 in the nucleus. A bulk western for 'NFKB1' cannot distinguish them, and a bulk immunofluorescence cannot either unless the antibody is C-terminus-specific. This is the same measurement problem this graph records for KMT2A's N320 and C180 fragments.",
  "bounded": "No p105-versus-p50 ratio, and no nuclear-versus-cytoplasmic partition for either species, has been measured in any KMT2A-rearranged cell or under a menin inhibitor."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"NFKB1\"[tiab] OR \"p105\"[tiab] OR \"p50\"[tiab] OR \"KBF1\"[tiab])",
      "querytranslation": "\"NFKB1\"[Title/Abstract] OR \"p105\"[Title/Abstract] OR \"p50\"[Title/Abstract] OR \"KBF1\"[Title/Abstract]",
      "count": 13202,
      "role": "operand control AND a warning - see alias_precision_verdict"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 32,
      "title_check": "NOT USABLE as a count of NFKB1 subnuclear papers; the clause contains two mass labels that match unrelated proteins across the whole literature. No on-topic p50 subnuclear compartment paper was identified.",
      "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 (nine-term KMT2A/MLL fusion clause)",
      "count": 4,
      "title_check": "PMIDs 37393343, 30122879, 17410185, 3608601 - none a p50 or p105 localisation measurement in a fusion-bearing cell.",
      "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": 1,
      "title_check": "PMID 37393343 only; off beat for this question.",
      "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_precision_verdict": "THIS IS THE OPPOSITE FAILURE MODE FROM HCFC2 IN THE SAME TRANCHE, and running both in one beat is the argument for treating the alias question per-gene. For HCFC2 the alternate name was the ONLY route to the answer (0 records under the HGNC symbol, 2 under HCF-2, and those 2 are the whole subnuclear literature). For NFKB1 the alternate names INFLATE catastrophically: 'p50' and 'p105' are apparent molecular masses reused by dozens of unrelated proteins, so a 13,202-record operand control and a 32-record subnuclear count are noise wearing the shape of data. The standing rule that a short or word-like alias must be title-checked before counting applies with full force, and the checked yield here is zero.",
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "never-measured"
}