Oncofusion

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Geneunrated confidence 0 of 5: unrated

KAT6A / MOZ — the acetyltransferase that is a fusion oncogene in its own right

also called KAT6A · MOZ · MYST3 · ZNF220 · RUNXBP2

KAT6A is an enzyme that tags chromatin to switch genes on. When it is joined to other genes it causes its own kind of leukaemia, and our unbiased scan says KMT2A-rearranged cells need it more than other leukaemia cells do.

The same thing, for a scientist

KAT6A (MOZ) is a MYST-family lysine acetyltransferase and a recurrent fusion partner in its own right: **KAT6A-CBP and KAT6A-P300 fusions are recurrent in AML with poor prognosis**. Those chimeras localise preferentially to **H3K4me2/3-marked regions** and act through **NURF**, the H3K4me2/3 reader, forming a self-reinforcing module with MLL/COMPASS. It enters this graph by a second route: the unbiased selectivity triage places it among the top ten genes that are both selectively required in KMT2A-rearranged lines and quiet across normal tissue.

Go deeper
Why it matters here specifically

Two independent reasons, and they meet.

It is the other fusion in our own data. Last cycle's provenance sweep found that E-MTAB-3322, the deposition behind this graph's KDM4C and paralogue-buffering claims, is half MOZ-TIF2 — a KAT6A fusion — with MLL-GAS7 and MLL-AF9 making up the rest. An 'MLL fusion' citation resolving to a KAT6A fusion was the sharpest surprise of that sweep, and KAT6A had no entry in this graph at the time.

It converges on the same chromatin marks. KAT6A chimeras target H3K4me2/3 regions and work through NURF and MLL/COMPASS — the same H3K4 methylation machinery that the KMT2A N-terminus and the WRAD subunits operate on. Two different fusion oncoproteins reaching the same mark by different enzymes is the cross-family pattern this project collects.

Facts and figures
uniprotQ92794
length AA2004
gene primaryKAT6A
accession addedverified against live UniProt 2026-09-20; rules 66/68/69 require accession AND length_aa so verify-accessions.py can fail a swap
gene symbolKAT6A
gene symbol notepromoted from gene_primary 2026-09-20: verify-accessions.py reads data.gene_symbol, so a gene_primary-only entry was being length-checked or id-inferred rather than symbol-asserted
uniprot synonyms
[
  "MOZ",
  "MYST3",
  "RUNXBP2",
  "ZNF220"
]
depmap kmt2a selectivity
{
  "chronos_mean_kmt2a_rearranged": -0.4294,
  "chronos_mean_other_leukaemia": -0.1441,
  "difference": -0.2853,
  "pan_essentiality_all_lines": -0.0949,
  "selectivity_rank": 106,
  "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
  • NURF bromodomain inhibition is an intervention this entry mentions and does not endorse: the compound, its potency and its selectivity are in a full text nobody here has read.
  • Every functional claim in this entry comes from murine myeloid KAT6A-fusion models. Nothing here has been shown in KMT2A::AFF1, in B-lymphoid cells, or in infant material.
  • The selectivity number rests on 11 cell lines, none infant-derived.
Still open
  1. Read PMC for PMID 40830799 and name the NURF/BPTF inhibitor, its potency and whether the effect survives in KMT2A-rearranged rather than KAT6A-rearranged cells.
  2. Does the KAT6A dependency in KMT2A-rearranged lines depend on the KMT2A fusion, or is it a myeloid-lineage effect? The 11-line panel is lineage-mixed and the split was not run.
  3. Re-examine the KDM4C and paralogue-buffering entries now that KAT6A has an entry: half their underlying deposition is a MOZ-TIF2 fusion and the two facts should be linked, not parallel.
Every source behind this entry (2)
  1. E1strong confidence 4 of 5: Replicated in peer-reviewed work by more than one group.paper

    KAT6A-CBP and KAT6A-P300 fusions are recurrent genetic alterations in AML associated with poor prognosis. De novo murine models built by domain-focused truncation recapitulate the morphological, immunophenotypic and transcriptomic features of KAT6A-rearranged AML; the fusions preferentially localise to H3K4me2/3-marked regions; and KAT6A interacts with the Nucleosome Remodeling Factor (NURF), an H3K4me2/3 reader, whose chromatin interaction can be disrupted by depletion or by small-molecule inhibition of its bromodomain subunit.

    PMID 40830799DOI
    What this evidence cannot show

    Abstract read from the NCBI efetch record on 2026-09-20; full text not read, so the identity of the small-molecule inhibitor, its potency and the extent of the phenotype are not recorded and must not be quoted from this item. The models are **murine and myeloid**, and built from truncated rather than full-length fusions because of the proteins' size — a design choice the authors state and whose consequences for fidelity are not assessed here. Nothing in this paper concerns KMT2A::AFF1 or B-lymphoid disease.

    Evidence that argues against this (1)
    • This is a KAT6A-fusion paper, not a KMT2A paper, and every transfer to this project's index disease crosses fusion, species and lineage at once — the exact import pattern the partner-provenance audit found in 54% of load-bearing evidence here. The shared H3K4me2/3 target is a point of convergence, not evidence that KAT6A does anything in KMT2A::AFF1 cells. Oncofusion knowledge graph (internal analysis) 2026
  2. E2moderate confidence 3 of 5: One strong study, or several smaller consistent ones.analysis

    DepMap gene effect in the 11 Cellosaurus-annotated KMT2A-rearranged leukemia lines is -0.429 against -0.144 in 43 other leukemia lines, a difference of -0.285, ranking 106 of 17,728 protein-coding genes scanned; mean effect across all lines is -0.095, so it is not pan-essential. GTEx v8 gives a whole-body median of 15.2 TPM across 54 tissues, a maximum of 23.4 TPM across brain, heart, blood, liver/kidney and endocrine tissue, and a peak of 29 TPM in Lung.

    What this evidence cannot show

    Selectivity read from the cached 17,728-gene scan on 2026-09-20 and expression queried from the GTEx API the same day; neither was recomputed here. **Eleven cell lines, none infant-derived**, carry the selectivity axis — the graph's standing weak spot — and GTEx is adult post-mortem tissue while the patients are infants. mRNA is not protein and neither is dependency.

    Evidence that argues against this (1)
    • A selectivity difference of this size sits well inside the range an unbiased scan of 17,728 genes produces by chance somewhere, which is why the scan reports an empirical p against its own distribution rather than a nominal one. KAT6A's position is interesting because of what is known about it, not because the number is extreme. Oncofusion knowledge graph (internal analysis) 2026
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