NASP - the soluble histone reservoir, and the only gene in this beat with a real selective difference at a pan-essentiality shallow enough to interpret

[
  "sNASP (somatic)",
  "tNASP (testis)"
]

{
  "index_mean": -0.5648,
  "other_leukaemia_mean": -0.4016,
  "difference": -0.1632,
  "pan_essentiality": -0.4634,
  "myeloid_difference": -0.1185,
  "lymphoid_difference": -0.2489,
  "n_index": 11
}

{
  "chronos_mean_kmt2a_rearranged": -0.5648,
  "chronos_mean_other_leukaemia": -0.4016,
  "difference": -0.1632,
  "pan_essentiality_all_lines": -0.4634,
  "selectivity_rank": 397,
  "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": "CYTOPLASM AND NUCLEUS - and on the HUMAN record there is no experimental evidence for either. UniProt P49321 (fetched live 2026-09-21) carries 'Cytoplasm' and 'Nucleus', both on a single ECO:0000250 attributed to Q99MD9, plus a nuclear localization signal annotated at residues 716-722. Q99MD9 was fetched and read back in the same session: it is NASP_MOUSE, 773 aa against the human 788, and the mouse record carries the SAME two values on THREE independent ECO:0000269 citations - PubMed:10893414, 12509435 and 16728391 [E_q93_nasp_loc1].",
  "AND_THIS_IS_THE_INVERTING_CASE_THE_BRIEF_ASKED_FOR": "Opening the propagation chain IMPROVED the annotation instead of weakening it. The third mouse citation, PubMed:12509435, is not a mouse experiment at all: full-length tNASP fused to GFP TRANSFECTED INTO HeLa CELLS is efficiently transported into the nucleus within 2 h of translation in the cytoplasm, whereas an NLS-DELETION MUTANT IS RETAINED IN THE CYTOPLASM [E_q93_nasp_loc3]. That is a human-cell, NLS-resolved import experiment with a matched negative control, sitting behind a human ECO:0000250 that reads as though nothing human had been done. THIS IS THE THIRD RODENT-PROPAGATION CHAIN THIS BEAT HAS OPENED IN TWO TRANCHES AND THE FIRST WHERE THE CHAIN LED SOMEWHERE BETTER THAN THE LABEL.",
  "ISOFORM_SCOPED_AND_UNIPROT_FLATTENS_IT": "There are two major forms and they are not interchangeable: tNASP in gametes, embryonic cells and transformed cells, and sNASP in all rapidly dividing somatic cells, sNASP being a shorter splice form with two coding deletions [E_q93_nasp_loc2]. UniProt's tissue comment records only that 'Isoform 1 is testis- and sperm-specific'. The compartment experiments were done on tNASP-GFP; the form present in a leukaemic blast is sNASP, and it has never been localised. Same shape as KMT2A's fragments, DNMT3A's isoforms and CD33's isoforms elsewhere in this graph.",
  "how_shown": "GFP-tNASP transfection into HeLa with an NLS-deletion negative control (PMID 12509435); affinity chromatography and histone isolation establishing the H1-only complex in myeloma cells (PMID 10893414); knockdown in HeLa and U2OS plus a null mouse (PMID 16728391)",
  "systems": "HeLa and U2OS human lines, mouse embryonic cells, and MYELOMA CELLS for the histone-binding work - which is the only haematopoietic system in the set. No leukaemic cell, no KMT2A-rearranged cell",
  "node": "localization-chromatin-bound-versus-soluble-fraction-kmt2a"
}

{
  "measured_in": "HeLa and U2OS for the import and knockdown work; MYELOMA CELLS for the histone-binding characterisation, which is the only haematopoietic system in the localisation literature for this gene [E_q93_nasp_loc2]; mouse embryonic cells and a NASP-null mouse.",
  "expressed_in": "sNASP is present in ALL MITOTIC CELLS EXAMINED, including mouse embryonic cells and several mouse and human tissue culture lines [E_q93_nasp_loc2] - so the cell-type answer for the somatic form is 'every dividing cell', and the informative statement is the isoform split rather than a tissue.",
  "in_this_disease": "NOTHING. There is no NASP image, fractionation or compartment measurement in any leukaemic cell, and this entry's existing data.kmt2a_literature_records records how thin the fusion-context literature is.",
  "the_requirement_is_real_and_general": "Without sufficient NASP, HeLa and U2OS cells cannot replicate their DNA or progress through the cell cycle, and the NASP-null mutation causes embryonic lethality [E_q93_nasp_loc4] - consistent with this entry's existing DepMap profile and with the brief's warning that a general proliferative requirement is not a disease-specific node."
}

{
  "CELL_CYCLE_IS_THE_DOCUMENTED_STATE": "NASP was characterised as a CELL-CYCLE-REGULATED somatic protein [E_q93_nasp_loc2], and overexpressing tNASP affects progression through the cell cycle [E_q93_nasp_loc3]. So the abundance of the reservoir protein is itself phase-dependent, which is exactly the variable this entry's existing argument needs: if H3K79 methylation is lost only when histones are replaced, the size and availability of the soluble pool is a rate term, and that rate term oscillates.",
  "TRANSFORMATION_IS_THE_SECOND_STATE_AND_IT_IS_AN_ISOFORM_SWITCH": "tNASP is found in gametes, embryonic cells AND TRANSFORMED CELLS, while sNASP is the form in rapidly dividing somatic cells [E_q93_nasp_loc2]. A transformed cell is therefore expected to carry the isoform whose nuclear import was actually measured - which is a rare case in this beat where the relevant isoform in a malignant cell may be the one with the data, and it has never been checked in a leukaemic blast.",
  "bounded": "No NASP cell-state or localisation measurement exists in any leukaemic cell, and the tNASP-to-sNASP ratio has never been measured in a KMT2A-rearranged sample."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"NASP\"[tiab] OR \"sNASP\"[tiab] OR \"tNASP\"[tiab])",
      "querytranslation": "\"NASP\"[Title/Abstract] OR \"sNASP\"[Title/Abstract] OR \"tNASP\"[Title/Abstract]",
      "count": 201,
      "role": "operand control"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 2,
      "title_check": "0 on topic for a NASP compartment. PMID 36868228 (DAXX adds a de novo H3.3K9me3 deposition pathway to the histone chaperone network) and PMID 23325853 (Nap1 and CENP-B binding to nucleosomes).",
      "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": 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."
    },
    {
      "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."
    },
    {
      "query": "NASP[tiab] AND (nuclear[tiab] OR nucleus[tiab] OR cytoplasm[tiab])",
      "querytranslation": "\"NASP\"[Title/Abstract] AND (\"nuclear\"[Title/Abstract] OR \"nucleus\"[Title/Abstract] OR \"cytoplasm\"[Title/Abstract])",
      "count": 65,
      "role": "inflated by the protein's own name - Nuclear Autoantigenic Sperm Protein contains the word nuclear, so the term matches the expansion of the acronym in essentially every paper about it. Not usable as a localisation count."
    }
  ],
  "acronym_trap": "NASP EXPANDS TO 'NUCLEAR AUTOANTIGENIC SPERM PROTEIN'. Any query pairing this symbol with 'nuclear' matches papers that merely spell the name out, so a 65-record count means nothing. This is the mirror of the contaminated-token problem elsewhere in this tranche: there the off-topic literature supplied the word, here the gene's own name does.",
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "never-measured"
}