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Geneweak confidence 2 of 5: Preliminary, small, indirect, or not yet peer reviewed.Q6-interactome-rna-layer

ZC3H13 — the m6A writer subunit with the most evenly KMT2A-selective dependency signal in the panel, and almost no literature

also called KIAA0853 · Flacc · zinc finger CCCH-type containing 13

ZC3H13 helps anchor the RNA-tagging machine in the nucleus. It is one of the few genes in this survey that KMT2A-rearranged cells need a bit more than others in both the myeloid and the B-cell halves, and almost nobody has studied it.

The same thing, for a scientist

ZC3H13 is a nuclear anchoring subunit of the m6A methyltransferase complex. It has one direct AML study, in which it facilitates progression through m6A-FOXP1-mediated metabolic reprogramming [E1]. It is one of only a handful of panel genes whose KMT2A-rearranged index-arm difference is negative and comparable in **both** lineage halves - -0.182 B-lymphoid and -0.157 myeloid, the 2.8th percentile of a 466-gene null, with 30.5% of 1,208 lines depleted so there is real dynamic range [E2]. Against MLL or KMT2A the literature is two records over two aliases [E3].

Go deeper
Why lineage concordance is the property worth noticing

Thirty of the 79 genes in this beat's scan have lymphoid and myeloid differences of opposite sign 2. For those, the pooled index-arm number is an average of two contradictory results and means nothing.

ZC3H13 is not one of them. Its two halves agree closely (-0.182 and -0.157), it is not floor-compressed, and it sits at the 2.8th percentile of the null. In a beat whose headline finding is that nothing in the RNA layer is menin-grade, ZC3H13 is among the few genes whose modest signal is at least internally consistent.

That is a reason to look, not a result. The effect size is roughly 2.3 null standard deviations on eleven cell lines, and the gene has one paper.

How thin the literature actually is

ZC3H13 AND leukemia returns 9 records; title-checked, most are m6A-regulator prognostic signature papers - the genre in which a panel of twenty m6A genes is fitted to survival data - rather than functional studies. The one functional AML paper is 1. (MLL OR KMT2A) AND (ZC3H13 OR KIAA0853) returns 2 3.

Prognostic-signature papers deserve a specific caution: a gene appearing in an m6A-regulator signature has been selected by a fitting procedure from a pre-specified list, and its appearance carries almost no information about mechanism. Several of this gene's nine records are of that kind and none of them is cited here.

Facts and figures
uniprotQ5T200
length AA1668
gene symbolZC3H13
uniprot resolutiongene_exact:ZC3H13 AND organism_id:9606 AND reviewed:true; one hit; primary gene name read back as ZC3H13; length 1668 aa checked
rna functionnuclear anchoring subunit of the m6A methyltransferase complex
essentiality
{
  "depmap_common_essential": false,
  "chronos_mean": -0.3883,
  "pct_lines_depleted": 30.5,
  "n_lines": 1208,
  "kmt2a_r_lymphoid_diff": -0.1817,
  "kmt2a_r_myeloid_diff": -0.1573,
  "null_percentile": 2.79,
  "lineage_discordant": false,
  "floor_compressed": false
}
pubmed counts
{
  "ZC3H13 AND (leukemia OR hematopoiesis)": 9,
  "(MLL OR KMT2A) AND (ZC3H13 OR KIAA0853)": 2
}
depmap kmt2a selectivity
{
  "chronos_mean_kmt2a_rearranged": -0.51,
  "chronos_mean_other_leukaemia": -0.3438,
  "difference": -0.1662,
  "pan_essentiality_all_lines": -0.3883,
  "selectivity_rank": 380,
  "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."
}
How this could bite us back
  • A 1,668-residue nuclear scaffold with no catalytic site is not a small-molecule target on any current evidence.
  • The signal being reported is roughly a fifth of menin's. Anything built on it would be a combination argument at best.
  • Selecting a gene for lineage concordance across a 79-gene panel is multiple comparisons; the honest status of this entry is 'worth one experiment', not 'a hit'.
Still open
  1. Is ZC3H13's lineage-concordant KMT2A-rearranged signal real, or is it one of the concordances expected by chance across 79 genes?
  2. Does ZC3H13 depletion in a KMT2A::AFF1 line reproduce anything of the AML metabolic phenotype?
Every source behind this entry (4)
  1. E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper

    ZC3H13 facilitates the progression of acute myeloid leukaemia through m6A-FOXP1-mediated metabolic reprogramming.

    PMID 40780498DOI
    What this evidence cannot show

    Abstract-level; a single 2025 study in AML, not independently reproduced, and not in KMT2A-rearranged B-lymphoid disease. A metabolic-reprogramming mechanism is among the harder ones to attribute specifically, because any growth perturbation changes metabolism.

    Evidence that argues against this (1)
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis

    DepMap CRISPR (Chronos) gives ZC3H13 a mean gene effect of -0.388 across 1,208 lines with 30.5% depleted below -0.5, and index-arm differences of -0.182 (four B-lymphoid) and -0.157 (seven myeloid) against 43 other leukaemia lines, at the 2.8th percentile of a 466-gene null (SD 0.075). It is lineage-concordant and not floor-compressed, unlike 30 of the 79 panel genes which are lineage-discordant.

    What this evidence cannot show

    Eleven index lines. A -0.17 Chronos difference is small in absolute terms and is being reported because its two halves agree, not because it is large.

    Evidence that argues against this (1)
    • Menin is -0.871 / -0.863 in the same comparison, five times larger. Picking out lineage-concordant genes from a 79-gene panel is a selection over many comparisons and some concordance will occur by chance. Oncofusion knowledge graph (internal analysis) 2026
  3. E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database

    Counted absence: `(MLL OR KMT2A) AND (ZC3H13 OR KIAA0853)` returns 2 PubMed records and `ZC3H13 AND (leukemia OR hematopoiesis)` returns 9, of which most are m6A-regulator prognostic signature papers rather than functional studies.

    PubMed E-utilities esearch counts, alias-expanded and title-checked · NCBI PubMed (queries run 2026-09-20) 2026
    What this evidence cannot show

    Two aliases covered. The distinction between signature papers and functional studies was made by reading titles, not full texts, so the classification is approximate.

    Evidence that argues against this (1)
    • Dismissing prognostic-signature papers as uninformative is a judgement, not a measurement. One of them could contain a real subtype-specific observation in a figure that the title does not advertise. Wang J et al. 2025
  4. E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database

    UniProtKB Q5T200 (ZC3HD_HUMAN) is human ZC3H13, 1668 amino acids; resolved by gene_exact query with the primary gene name read back as ZC3H13 and the length checked.

    What this evidence cannot show

    Single reviewed human hit whose primary gene name equals the query symbol. This project has logged six cases of gene_exact returning a protein that merely lists the queried symbol as a synonym, so the read-back is the point, not the query.

    Evidence that argues against this (1)
    • An accession establishes identity and length. It says nothing about whether this protein matters in KMT2A-rearranged leukaemia, which is what the rest of this entry is for. UniProt Consortium 2026
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