CSNK2A2 - CK2's other catalytic subunit, expressed in every KMT2A-rearranged line and, if anything, slightly favourable to lose

{
  "question": "Is CSNK2A2's flat/positive dependency an expression artefact?",
  "answer": "No - detected in 7/7 KMT2A-rearranged panel lines, median 22.1 nTPM, though roughly fourfold below CSNK2A1",
  "source": "Human Protein Atlas rna_celline.tsv, filtered 2026-09-20"
}

{
  "chronos_mean": -0.0045,
  "n_lines": 1208,
  "chronos_mean_kmt2ar_myeloid": 0.1447,
  "chronos_mean_kmt2ar_lymphoid": 0.1002,
  "chronos_mean_other_leukemia": -0.0145,
  "scan_rank": 17446,
  "scan_n_genes": 17728,
  "difference": 0.1489
}

{
  "SEM": 22.1,
  "RS4;11": 44.1,
  "MV4-11": 31.3,
  "THP-1": 17.1,
  "NOMO-1": 16,
  "MOLM-13": 12.2,
  "OCI-AML-2": 27.9,
  "median": 22.1
}

[
  "gene-csnk2a1",
  "mechanism-cdk9-phosphorylates-aff4-sec-assembly"
]

{
  "chronos_mean_kmt2a_rearranged": 0.1302,
  "chronos_mean_other_leukaemia": -0.0187,
  "difference": 0.1489,
  "pan_essentiality_all_lines": -0.0045,
  "selectivity_rank": 17446,
  "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 - AND THERE IS NO HUMAN EXPERIMENTAL EVIDENCE FOR EITHER. UniProt P19784 (fetched live 2026-09-21) carries two location values, 'Nucleus' and 'Cytoplasm', BOTH on a single ECO:0000250 attributed to O54833, with the note 'Interaction with SIRT6 prevents translocation into the nucleus'. O54833 was fetched and read back in the same session: it is CSK22_MOUSE, the mouse orthologue, 350 aa - IDENTICAL IN LENGTH TO THE HUMAN PROTEIN - and the mouse record's own nucleus and cytoplasm calls rest on one ECO:0000269, PubMed:28355567 [E_q93_csnk2a2_loc1].",
  "WHAT_28355567_ACTUALLY_IS": "'SIRT6 Is Essential for Adipocyte Differentiation by Regulating Mitotic Clonal Expansion' (Cell Reports 2017) - an ADIPOGENESIS paper whose subject is SIRT6, KIF5C and preadipocyte differentiation [E_q93_csnk2a2_loc2]. So the compartment record for human CK2alpha-prime is: human <- mouse by similarity <- one adipocyte-differentiation study. It is the third cross-species two-step chain this beat has found in two tranches, after SGF29 (human <- rat <- one hepatocellular-carcinoma paper) and CTR9 (human <- mouse <- one 1996 SH2-binding cloning paper).",
  "AND_THE_PARALOGUE_HAS_THE_BETTER_RECORD_WHICH_IS_THE_SAME_ASYMMETRY_THIS_ENTRY_ALREADY_DOCUMENTS": "gene-csnk2a1 carries a measured, quantified and prognostically scored subnuclear pool - NUCLEOLAR CK2alpha in 50.8% of 118 resected lung adenocarcinomas, an independent predictor of worse recurrence-free survival. CK2alpha-prime has no human compartment measurement at all. This entry's whole argument is that CSNK2A1 reaches KMT2A biology by three independent routes and none has been tested with CSNK2A2; the localisation record has exactly the same shape, and is a fourth instance of the same asymmetry.",
  "how_shown": "nothing in a human cell. UniProt ECO:0000250 by similarity from mouse; the mouse call is from an adipocyte-differentiation study",
  "systems": "mouse preadipocytes for the propagated call; mouse testis for the only compartment-adjacent CK2alpha-prime phenotype. No human cell, no haematopoietic cell, no leukaemic cell",
  "node": "localization-nucleolus-kmt2a-fusion"
}

{
  "measured_in": "mouse preadipocytes for the propagated compartment call; MOUSE TESTIS for the null phenotype. UniProt P19784 carries no tissue-specificity comment, but the Csnk2a2-null paper states that this subunit is PREDOMINANTLY EXPRESSED IN TESTIS [E_q93_csnk2a2_loc4] - which is the informative expression fact for this gene and is absent from the UniProt record.",
  "in_leukaemia": "This entry's existing content supplies the leukaemia cell-type answer and it is a negative one: CSNK2A2 is expressed in every KMT2A-rearranged line by HPA cell-line nTPM, and removing it does not hurt those cells and may help them slightly. Expression without requirement. There is no CK2alpha-prime image, fractionation or compartment measurement in any leukaemic cell.",
  "the_testis_point_matters_for_the_CK2_hypothesis": "hyp-ck2-is-the-second-handle-on-the-retained-fragment and mechanism-ck2-t2724-s2726-licenses-taspase1-cleavage are built on CK2 activity, and the published chemistry (CX-4945, TBB, DMAT) is pan-catalytic-subunit, so those entries cannot attribute to a subunit. If the alpha-prime subunit's principal tissue is testis while alpha is ubiquitous, then a CK2 activity measured in a leukaemic cell is overwhelmingly likely to be alpha's - which supports rather than undermines those entries' implicit attribution, and is the first piece of evidence in this graph that bears on it."
}

{
  "state": "NO CK2alpha-prime-DEFINED CELL STATE IS RECORDED HERE, and the honest reason is that the only organismal phenotype is gametogenic. Male mice lacking Csnk2a2 are infertile with oligozoospermia and abnormally shaped spermatid nuclei, and the null testes show germ-cell degeneration at all stages including the first spermatogenic wave [E_q93_csnk2a2_loc4]. That is a differentiation failure in a lineage this project will never study.",
  "the_one_STATE_variable_that_transfers_is_the_SIRT6_switch": "UniProt's note - 'Interaction with SIRT6 prevents translocation into the nucleus' - describes a regulated partition, and it comes from the adipogenesis paper [E_q93_csnk2a2_loc2]. SIRT6 is an NAD+-dependent deacetylase, so if the note is right the nuclear entry of this subunit is coupled to NAD+ metabolism. NOTHING OF THIS HAS BEEN TESTED IN A HUMAN CELL and the note is carried on an ECO:0000250 chain, so it is recorded as a hypothesis-generating annotation rather than a fact.",
  "bounded": "No CSNK2A2 cell-state or localisation measurement exists in any haematopoietic or leukaemic cell, and nothing under a menin inhibitor."
}

{
  "date": "2026-09-21",
  "tool": "NCBI E-utilities esearch, db=pubmed",
  "run_by": "Q93",
  "queries": [
    {
      "query": "(\"CSNK2A2\"[tiab] OR \"CK2alpha'\"[tiab] OR \"casein kinase 2 alpha prime\"[tiab])",
      "querytranslation": "\"CSNK2A2\"[Title/Abstract] OR \"ck2alpha\"[Title/Abstract] OR \"casein kinase 2 alpha prime\"[Title/Abstract]",
      "count": 859,
      "role": "operand control - AND THE TRANSLATION IS THE FINDING, see apostrophe_trap below"
    },
    {
      "query": "(gene clause) AND (twelve-term subnuclear clause)",
      "count": 23,
      "title_check": "not usable, because the clause collapsed alpha and alpha-prime; no CK2alpha-prime-specific subnuclear 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": "CSNK2A2[tiab] AND (nucleus[tiab] OR nuclear[tiab] OR cytoplasm[tiab])",
      "querytranslation": "\"CSNK2A2\"[Title/Abstract] AND (\"nucleus\"[Title/Abstract] OR \"nuclear\"[Title/Abstract] OR \"cytoplasm\"[Title/Abstract])",
      "count": 5,
      "title_check": "0 are CK2alpha-prime localisation studies. PMIDs 42674201 (knee osteoarthritis Wnt/NF-kB), 34039950 (EBV-positive DLBCL genomics), 25837326 (CDK11 and CK2 RNAi in triple-negative breast cancer), 17903308 (sleep and circadian GWAS), 12950107 (Csnk2a2-null spermatogenesis - the only compartment-adjacent one)."
    },
    {
      "query": "(gene clause) AND (nine-term KMT2A/MLL fusion clause)",
      "count": 2,
      "title_check": "PMIDs 34039950 and 25136288; neither a localisation study.",
      "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."
    }
  ],
  "APOSTROPHE_TRAP_NEW_AND_WORTH_THE_COLLISION_REGISTRY": "PubMed STRIPS THE PRIME. The query string \"CK2alpha'\"[tiab] comes back in querytranslation as \"ck2alpha\"[Title/Abstract] - the apostrophe is removed and the term silently becomes the name of the OTHER catalytic subunit. So the single most natural way to search for this protein by its protein name retrieves CK2alpha and CK2alpha-prime together, with no warning and no way to separate them after the fact. That is why the 859-record operand control and the 23-record subnuclear count above are reported as unusable, and why the counts this entry relies on are keyed to the HGNC symbol CSNK2A2 only. This compounds the collision already logged in data/symbol-collisions.json, where CSNK2A1 is an ALIAS SYMBOL of CSNK2A2 (brief rule 63): the databases alias the two subunits into each other, the published chemistry cannot separate them, and now the literature index cannot either. THREE INDEPENDENT INSTRUMENTS FAIL ON THE SAME DISTINCTION.",
  "reading": "Titles and abstracts only; supporting figures not searched (brief rule 80).",
  "absence_class": "never-measured"
}