KAT8

Chr 16AD

lysine acetyltransferase 8

Also known as: LIGOWS, MOF, MYST1, ZC2HC8, hMOF

The protein is a histone acetyltransferase that modifies chromatin structure through acetylation of histones, containing a MYST domain with an acetyl-CoA-binding site and chromodomain for histone binding. Mutations cause Li-Ghorgani-Weisz-Hubshman syndrome through an autosomal dominant inheritance pattern. The pathogenic mechanism involves disrupted chromatin regulation affecting gene expression.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismADLOEUF 0.481 OMIM phenotype
Clinical SummaryKAT8
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Missense constrained — critical functional residues
LoF Constraint
0.48LOEUF
pLI 0.225
Z-score 3.49
OE 0.24 (0.130.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
3.15Z-score
OE missense 0.45 (0.390.53)
118 obs / 261.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.24 (0.130.48)
00.351.4
Missense OE0.45 (0.390.53)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 6 / 24.7Missense obs/exp: 118 / 261.3Syn Z: 0.20
DN
0.4883th %ile
GOF
0.4974th %ile
LOF
0.4825th %ile

The Badonyi & Marsh model scores gain-of-function highest, but genomic evidence most strongly supports dominant-negative as the primary mechanism.

DN1 literature citation

Literature Evidence

DNBlocking the radiation-induced increase in histone H4 acetylation, either by expression of a dominant-negative MOF mutant or by MOF RNA interference, resulted in decreased ATM kinase activity and autophosphorylation, decreased phosphorylation of downstream effectors of ATM and DNA repair, and increaPMID:15923642

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

KAT8 · 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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