KAT6A

Chr 8AD

lysine acetyltransferase 6A

Also known as: ARTHS, MOZ, MRD32, MYST-3, MYST3, RUNXBP2, ZC2HC6A, ZNF220

This histone acetyltransferase acetylates lysine-9 residues in histone 3 and acts as a co-activator for transcription factors, playing a critical role in gene regulation. Mutations cause Arboleda-Tham syndrome, an autosomal dominant neurodevelopmental disorder characterized by intellectual disability, predominantly through loss-of-function mechanisms. The gene shows extreme intolerance to loss-of-function variants, consistent with haploinsufficiency as the primary disease mechanism.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.071 OMIM phenotype
Clinical SummaryKAT6A
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Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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GeneReview available — KAT6A
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 8.67
OE 0.02 (0.010.07)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint
2.07Z-score
OE missense 0.83 (0.780.87)
925 obs / 1120.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.02 (0.010.07)
00.351.4
Missense OE0.83 (0.780.87)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 2 / 91.6Missense obs/exp: 925 / 1120.1Syn Z: 0.04
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveKAT6A-related intellectual developmental disorderLOFAD
DN
0.11100th %ile
GOF
0.1699th %ile
LOF
0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.07

Literature Evidence

LOFDominant mutations in KAT6A cause intellectual disability with recognizable syndromic featuresPMID:25728777

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KAT6A · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗