RYBP - the subunit that makes a variant PRC1 complex catalytically active, named by two entries in this graph and never written

[
  "DEDAF",
  "YEAF1"
]

[
  "variant PRC1 (RYBP-PRC1)",
  "PRC1.1 / BCOR complex"
]

[
  "gene-rnf2",
  "gene-pcgf1",
  "gene-bcor",
  "RING1"
]

{
  "rybp_and_mll_or_kmt2a": 0,
  "rybp_and_leukemia": 1,
  "pcgf1_and_leukemia_control": 6,
  "prc1_1_complex_form": 11,
  "reachable_only_via": [
    "mixed-lineage leukemia",
    "AF9"
  ]
}

{
  "subcellular": "NUCLEUS AND CYTOPLASM, both at ECO:0000269 in UniProt Q8N488 (fetched 2026-09-21), plus 'Nucleus, nucleoplasm' at ECO:0000250 (by similarity, NOT experimental). The cytoplasmic pool is experimental and is easy to forget for a protein the graph treats as a Polycomb subunit; RYBP's alias DEDAF (death effector domain-associated factor) comes from that non-Polycomb biology.",
  "subnuclear": "NOT DIRECTLY MEASURED, and the one nucleoplasmic annotation UniProt carries is ECO:0000250 - inferred by similarity, not experimental. Any Polycomb-body attribution for RYBP in this graph would be a complex-to-subunit transfer: the existing localization-polycomb-bodies-kmt2a-r entry already records that the graph's Polycomb-body evidence is indirect, via CBX8, and is undercut by CBX8-PRC1 condensates being dissolved rather than built by the rest of PRC1.",
  "explicit_no": "SAY IT PLAINLY: no experimental subnuclear localisation for RYBP exists in any system, and nothing at all in a KMT2A-rearranged cell. UNPUBLISHED rather than not-applicable - RYBP is a 228-residue nuclear protein and Polycomb bodies are exactly where one would look.",
  "how_shown": "UniProt Q8N488 SUBCELLULAR LOCATION comment, fetched 2026-09-21; Nucleus and Cytoplasm at ECO:0000269, nucleoplasm at ECO:0000250",
  "systems": "no haematopoietic or KMT2A-rearranged localisation system at all",
  "shown_for_fusion_localisation": "no",
  "node": "localization-polycomb-bodies-kmt2a-r"
}

{
  "evidence_class_key": "concept-expressed-required-maintains-three-evidence-classes",
  "identifier_note": "RYBP (Q8N488, 228 aa, 'RING1 and YY1-binding protein', synonyms DEDAF and YEAF1) is not YAF2, its paralogue, which this entry already records. Note that RYBP's synonym DEDAF belongs to an apoptosis literature that has nothing to do with Polycomb, so a token search on DEDAF returns a different field.",
  "expressed_in": {
    "class": 1,
    "summary": "broadly expressed; a variant-PRC1 subunit, not a lineage-restricted factor."
  },
  "required_in": {
    "class": 2,
    "claim": "In MICE, Rybp is required THROUGHOUT ADULT LIFE to sustain the B-1-to-B-2 B-cell progenitor switch: conditional inactivation reverts the ratio toward the innate, predominantly fetal B-1 progenitors and LOSES PRE-PRO-B CELLS, and both LKS stem/progenitor populations and isolated common lymphoid progenitors produce excess B-1 progenitors in vitro [E_q71_ct1].",
    "pmids": [
      "26711264"
    ],
    "system_named_in_the_claim": "murine conditional Rybp inactivation in normal adult haematopoiesis - no fusion present",
    "nodes": [
      "cell-type-clp",
      "cell-type-pre-pro-b"
    ],
    "node_caveat": "RESOLVED 2026-09-21 by Q73 - the vocabulary gap this field recorded is closed. cell-type-pre-pro-b (murine Hardy Fraction A) now exists and this entry points at it instead of at cell-type-pro-b, which had been used as a stated approximation. Two cautions travel with the new node. (1) cell-type-fetal-preprob-cd10-negative is the HUMAN fetal CD19+CD34+CD10-negative progenitor and is still not a substitute here: different species, different defining markers, different ontogenetic window. (2) The marker-defined Fraction A gate is NOT pure B-lineage - plasmacytoid dendritic cells were defined as a Ly-6C+ CD11c-low subset of B220+CD19-CD43+CD24-low Fraction A and are present in RAG1-/-, IL-7Ra-/- and Pax5-/- marrow (PMID 15728131) - so 'loss of pre-proB cells' scored by surface markers is a claim about a mixed population unless resolved by CD19, Ly-6C or Ig locus configuration."
  },
  "why_this_one_is_worth_more_than_its_confidence": "Nearly all this graph's cell-type evidence is myeloid, which brief rule 73 measures at 21% myeloid against 18% B-lineage in a B-lineage disease. This is a B-LINEAGE PROGENITOR result, and specifically about the FETAL-versus-ADULT B programme - the same axis as cell-state-fetal-program-retention, which this graph holds as central to infant KMT2A-rearranged disease.",
  "NO_DEPMAP_ROW": {
    "finding": "RYBP IS ABSENT FROM THIS PROJECT'S GENOME-WIDE SCAN. analyses/depmap-kmt2a-selective-scan-full scanned 17,728 genes and RYBP is not one of them, checked by exact symbol on 2026-09-21. The Q71 dispatch brief stated that every gene in its set carries data.depmap_kmt2a_selectivity; for RYBP the field is absent because the underlying row does not exist, not because a join was missed.",
    "what_not_to_do": "Do not fabricate a rank for this gene, and do not read the absence as 'not a dependency'. It is a missing measurement. The scan's 17,728 is a subset of DepMap's screened genes and a gene can be absent for library reasons."
  },
  "context": "murine normal adult haematopoiesis; no DepMap row exists"
}

{
  "evidence_class_key": "concept-expressed-required-maintains-three-evidence-classes",
  "maintains_state": {
    "class": 3,
    "states": [
      "cell-state-fetal-program-retention"
    ],
    "claim": "In MICE, Rybp SUSTAINS THE ADULT B-2 PROGRAMME AGAINST THE FETAL B-1 ONE: its inactivation in adult haematopoiesis reverts the B-1-to-B-2 progenitor ratio toward the innate, predominantly FETAL B-1 precursors [E_q71_ct1]. Losing RYBP therefore produces a fetal-programme-retaining state in a fusion-free animal - which is the same phenomenology this graph attributes to infant KMT2A-rearranged disease, reached by a completely different route.",
    "pmids": [
      "26711264"
    ],
    "system_named_in_the_claim": "murine conditional Rybp inactivation in normal adult haematopoiesis"
  },
  "the_lineage_versus_fusion_reading": "This is a direct test of the claim cycle 39 made. A fetal-programme-retention state, in B-lineage progenitors, in a mouse with NO fusion, produced by removing one chromatin protein. It does not show that the fusion is irrelevant, but it does show that this particular state does not require a fusion to exist - which is precisely the shape of the lineage explanation.",
  "confidence": "strong",
  "caveats": "Murine, normal haematopoiesis, adult rather than infant, and the B-1/B-2 distinction is a mouse immunology construct whose human counterpart is contested. The authors' own negatives - no global H2AUb change, no genetic interaction with Ring1A or Ring1B - mean the mechanism is unestablished even though the phenotype is clear.",
  "counter_evidence": {
    "note": "The authors' own controls are the counter-argument, and they are decisive about mechanism. Rybp inactivation did not alter global H2A monoubiquitylation and showed no genetic interaction with Ring1A or Ring1B deletion. This entry exists to record RYBP as the subunit that makes variant PRC1 catalytically active; the one adult haematopoietic experiment finds a B-lineage phenotype with no detectable catalytic signature. Either the relevant H2AUb change is local and invisible in a global assay, or the phenotype runs through something other than variant-PRC1 catalysis - and nothing published distinguishes those.",
    "citation": {
      "title": "Role of Polycomb RYBP in Maintaining the B-1-to-B-2 B-Cell Lineage Switch in Adult Hematopoiesis.",
      "authors": "Calés C, Pavón L, Starowicz K, Pérez C, Bravo M, Ikawa T, Koseki H, Vidal M",
      "year": 2015,
      "venue": "Mol Cell Biol",
      "pmid": "26711264",
      "doi": "10.1128/MCB.00869-15",
      "type": "paper"
    }
  }
}