WTAP — an oncogenic m6A writer subunit in AML with ZERO records against MLL or KMT2A over six aliases
also called FL2D · Mum2 · Wilms tumour 1-associating protein · WT1 associated protein
WTAP is the scaffolding part of the machine that tags messenger RNA, and it behaves as an oncogene in adult myeloid leukaemia. No published study has ever paired it with KMT2A-rearranged disease.
The same thing, for a scientist
WTAP is the regulatory subunit that recruits the METTL3-METTL14 catalytic core to nuclear speckles and to its substrates. It is described as a novel oncogenic protein in AML [E1]. Against this graph's index disease it is a clean counted absence: `(MLL OR KMT2A) AND (WTAP OR Wilms tumor 1 associating protein)` returns **0 records**, against 34 for `WTAP AND leukemia` [E2]. DepMap gives it a Chronos mean of -0.611 with 66.6% of 1,208 lines depleted and index-arm differences of -0.059 B-lymphoid / -0.164 myeloid, the 4.9th percentile of a 466-gene null [E3] - broadly required, mildly myeloid-leaning, not fusion-selective.
Why a 34-to-0 split is the interesting number
WTAP has a real leukaemia literature - 34 records - and exactly none of it touches MLL or KMT2A 2. That is a different shape of absence from a gene nobody studies. It says the field has decided WTAP is an AML gene and has never asked the subtype question, not that the question was asked and answered negatively.
An absence of testing is not a negative result, and this graph has had to correct entries that read one as the other.
The complex-level trap, restated because it applies here
WTAP, METTL3 and METTL14 are one machine. A subunit-keyed enumeration splits a single literature three ways and misses any paper that frames its result as 'the m6A methyltransferase complex' - a phrase that returns one leukaemia record in PubMed and no KMT2A-specific one 2.
This is the NSL-complex failure from cycle 45 in a new setting, and the reason all three subunits get separate entries in this beat with the complex phrase searched explicitly.
| uniprot | Q15007 |
|---|---|
| length AA | 396 |
| gene symbol | WTAP |
| uniprot resolution | gene_exact:WTAP AND organism_id:9606 AND reviewed:true; one hit; primary gene name read back as WTAP; length 396 aa checked |
| rna function | regulatory subunit of the m6A methyltransferase complex; recruits METTL3-METTL14 to nuclear speckles and substrates |
essentiality
{
"depmap_common_essential": false,
"chronos_mean": -0.6112,
"pct_lines_depleted": 66.6,
"n_lines": 1208,
"kmt2a_r_lymphoid_diff": -0.059,
"kmt2a_r_myeloid_diff": -0.1639,
"null_percentile": 4.94
}pubmed counts
{
"WTAP AND leukemia": 34,
"(MLL OR KMT2A) AND WTAP (alias-expanded)": 0
}depmap kmt2a selectivity
{
"chronos_mean_kmt2a_rearranged": -0.676,
"chronos_mean_other_leukaemia": -0.5502,
"difference": -0.1258,
"pan_essentiality_all_lines": -0.6112,
"selectivity_rank": 705,
"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."
}- Depleted in two-thirds of all DepMap lines - an essential-function toxicity risk before any disease argument.
- As a scaffolding subunit rather than a catalytic one, WTAP offers no obvious small-molecule pocket, so the existing METTL3 chemistry does not transfer.
- Does WTAP matter in KMT2A-rearranged leukaemia at all? Zero records is the entire published answer.
- Are the three m6A writer subunits separably required, or does any subunit knockout simply collapse complex activity?
- E1moderate confidence 3 of 5: One strong study, or several smaller consistent ones.paper
WTAP is a novel oncogenic protein in acute myeloid leukaemia.
WTAP is a novel oncogenic protein in acute myeloid leukemia · Bansal H, et al. · Leukemia 2014What this evidence cannot show
A 2014 Letter, abstract-level. AML. 'Oncogenic protein' in a letter format carries less mechanistic detail than the m6A field's later work, and WTAP's m6A role was not fully established at the time.
Evidence that argues against this (1)
- WTAP is depleted in 66.6% of all 1,208 DepMap lines with a Chronos mean of -0.611. A gene required by two-thirds of all cancer lines is a general requirement, and an 'oncogenic in AML' claim built on expression and knockdown in that setting cannot separate the two. Oncofusion knowledge graph (internal analysis) 2026
- E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.database
Counted absence: `(MLL OR KMT2A) AND WTAP` returns 0 PubMed records and the alias-expanded `(MLL OR KMT2A) AND (WTAP OR Wilms tumor 1 associating protein)` also returns 0, against 34 records for `WTAP AND leukemia`. The complex phrase `"m6A methyltransferase complex" AND leukemia` returns 1 record, not KMT2A-specific.
PubMed E-utilities esearch counts, alias-expanded and title-checked · NCBI PubMed (queries run 2026-09-20) 2026What this evidence cannot show
Symbol- and phrase-keyed. FL2D, the UniProt entry name, is not a commonly used literature alias and adds nothing; the substantive risk is a paper framed at complex level, which is why that phrase was run.
Evidence that argues against this (1)
- Zero records means nobody looked. It is not evidence that WTAP is dispensable in KMT2A-rearranged disease, and the DepMap row - a mild myeloid-leaning difference - is at least weakly compatible with a requirement nobody has tested. Oncofusion knowledge graph (internal analysis) 2026
- E3moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis
DepMap CRISPR (Chronos) gives WTAP a mean gene effect of -0.611 across 1,208 lines with 66.6% depleted below -0.5, and index-arm differences of -0.059 (four B-lymphoid) and -0.164 (seven myeloid) against 43 other leukaemia lines, at the 4.9th percentile of a 466-gene null.
The RNA layer in KMT2A-rearranged leukaemia lines: panel-wide selectivity scan and IGF2BP family co-dependency test · Oncofusion knowledge graph (internal analysis) 2026What this evidence cannot show
The percentile looks selective and the effect size does not: -0.164 Chronos against a null of SD 0.075, driven by the myeloid half, on seven lines.
Evidence that argues against this (1)
- At 66.6% of lines depleted WTAP is approaching the regime where the dynamic range for selectivity is small. This project flags floor compression at 90% but the compression is continuous, not a threshold. Oncofusion knowledge graph (internal analysis) 2026
- E4established confidence 5 of 5: Multiple independent lines of evidence; treated as settled in the field.database
UniProtKB Q15007 (FL2D_HUMAN) is human WTAP, 396 amino acids; resolved by gene_exact query with the primary gene name read back as WTAP and the length checked.
UniProtKB Q15007 (FL2D_HUMAN), human WTAP, 396 aa · UniProt Consortium 2026What 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
Regulatory subunit of the same m6A methyltransferase complex
Broadly required, myeloid-leaning, not fusion-selective
- ← related toRBM15 — m6A adaptor, AMKL fusion partner, and a named hit in the only KMT2A-biased RNA-protein CRISPR screen
RBM15 is a subunit of the WTAP complex with Hakai, Virilizer, KIAA0853, BCLAF1 and THRAP3 (PMID 24100041) - the complex through which its m6A adaptor function runs, and the route by which m6A deposition acquires a subnuclear address (Q91 2026-09-22)