SBDS - a ribosome-maturation factor whose loss causes a leukaemia-predisposition syndrome, and whose BioID neighbourhood contains AFF1, KMT2A, CDK9, PAF1 and LEDGF

[
  "AFF1",
  "CDK9",
  "KMT2A",
  "PSIP1",
  "PAF1",
  "ICE1",
  "WDR5",
  "SETD1A",
  "CDC73",
  "RTF1",
  "HCFC1",
  "HDAC1",
  "RUNX1",
  "IGF2BP2",
  "IGF2BP3"
]

{
  "chronos_mean_kmt2a_rearranged": -2.3082,
  "chronos_mean_other_leukaemia": -2.1164,
  "difference": -0.1917,
  "pan_essentiality_all_lines": -2.1324,
  "selectivity_rank": 280,
  "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": "PRIMARILY CYTOPLASMIC, WITH GENUINE NUCLEAR AND NUCLEOLAR POOLS AT LOW LEVEL, AND A MITOTIC-SPINDLE POOL. UniProt Q9Y3A5 (fetched live 2026-09-21) lists four values - 'Cytoplasm', 'Nucleus, nucleolus', 'Nucleus, nucleoplasm' and 'Cytoplasm, cytoskeleton, spindle' - and its note is cell-cycle-scoped and well-cited: primarily detected in the cytoplasm and at LOW LEVELS in nucleus and nucleolus (PubMed:17475909, PubMed:19602484); detected IN THE NUCLEOLUS DURING G1 AND G2 and DIFFUSELY DISTRIBUTED IN THE NUCLEUS DURING S PHASE; detected at the mitotic spindle; colocalising with the microtubule organizing center during interphase (PubMed:19759903) [E_q91_sbds_loc1].",
  "INTERPHASE_MTOC": "In interphase cells a PERINUCLEAR ENRICHMENT of SBDS protein was observed which co-localised with the microtubule organizing centre, and in-vitro binding studies show a DIRECT interaction of SBDS with microtubules [E_q91_sbds_loc3]."
}

{
  "HAEMATOPOIETIC_AND_PRIMARY_HUMAN_WHICH_IS_RARE_IN_THIS_TRANCHE": "SBDS RNA and protein are expressed in the human myeloid leukaemia line PLB-985 AND IN HUMAN HAEMATOPOIETIC PROGENITOR CELLS by quantitative RT-PCR and Western blot, and SBDS EXPRESSION IS DOWN-REGULATED DURING NEUTROPHIL DIFFERENTIATION. Immunofluorescence in that system showed SBDS co-localising with the mitotic spindle and, in interphase, perinuclear enrichment at the MTOC. Bone marrow haematopoietic progenitor cells from SDS patients showed reduced differentiation and proliferation capacity in liquid culture relative to controls [E_q91_sbds_loc3].",
  "germline_disease_cell_types": "Marrow failure with neutropenia and neutrophil chemotaxis defects, exocrine pancreas, and skeletal dysplasia; with a documented risk of MDS/AML transformation [E_q91_sbds_loc2][E_q91_sbds_loc3].",
  "the_bioid_caveat_this_entry_already_makes": "The AFF1/KMT2A/CDK9/LEDGF neighbourhood that put SBDS in this graph comes from an 828-prey BioID2 experiment in K562 - the second-largest neighbourhood in that dataset - and SBDS's established biology is cytoplasmic. The localisation record above sharpens rather than rescues that caveat: SBDS does have nuclear and nucleolar pools, but they are explicitly LOW-LEVEL, and a proximity-labelling bait with a small nuclear pool can still biotinylate a large number of nuclear proteins over a multi-hour window."
}

{
  "CELL_CYCLE": "Nucleolar in G1 and G2, diffusely nuclear in S phase, at the mitotic spindle in mitosis, at the MTOC in interphase [E_q91_sbds_loc1][E_q91_sbds_loc3]. Four positions in one cycle; no single resting-state answer is correct.",
  "rRNA_TRANSCRIPTION_STATE": "The nucleolar pool requires ACTIVE rRNA TRANSCRIPTION, and cells from SDS or Diamond-Blackfan anaemia patients are HYPERSENSITIVE to low doses of actinomycin D, an inhibitor of rRNA transcription [E_q91_sbds_loc2]. The compartment and the sensitivity are two readouts of the same dependence.",
  "DIFFERENTIATION_STATE": "SBDS expression falls during neutrophil differentiation [E_q91_sbds_loc3], so its abundance is a function of maturation stage - relevant to any comparison between blast and mature compartments."
}

{
  "date": "2026-09-22",
  "tool": "NCBI esearch db=pubmed",
  "run_by": "Q91",
  "queries": [
    {
      "query": "SBDS[tiab]",
      "querytranslation": "\"SBDS\"[Title/Abstract]",
      "count": 601,
      "role": "operand control"
    },
    {
      "query": "SBDS[tiab] AND nucleolus[tiab]",
      "querytranslation": "\"SBDS\"[Title/Abstract] AND \"nucleolus\"[Title/Abstract]",
      "count": 8,
      "role": "the nucleolar literature exists and is small and specific"
    },
    {
      "query": "SBDS[tiab] AND MLL[tiab]",
      "querytranslation": "\"SBDS\"[Title/Abstract] AND \"MLL\"[Title/Abstract]",
      "count": 0
    },
    {
      "query": "SBDS[tiab] AND KMT2A[tiab]",
      "querytranslation": "\"SBDS\"[Title/Abstract] AND \"KMT2A\"[Title/Abstract]",
      "count": 1,
      "title_read": true,
      "on_topic": false,
      "note": "an SDS sibling-pair exome study reporting an incidental germline KMT2A Wiedemann-Steiner variant. A count of 1 accepted without reading the title would have implied an SBDS-KMT2A link that does not exist."
    }
  ],
  "reading": "The absence is of any measurement in a fusion context. It is NOT an absence of localisation data - SBDS has one of the better-resolved localisation records in this tranche. Titles and abstracts only (rule 80). SDS, SWDS and CGI-97 were not run as separate operands; SDS in particular is unusable as a bare token (sodium dodecyl sulphate) and is a candidate row for the symbol-collision registry.",
  "absence_class": "never-measured"
}