KAT8

Chr 16AD

lysine acetyltransferase 8

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

NCBI Gene: 84148 ENSG00000103510 UniProt: Q9H7Z6 OMIM: 609912

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the MYST histone acetylase protein family. The encoded protein has a characteristic MYST domain containing an acetyl-CoA-binding site, a chromodomain typical of proteins which bind histones, and a C2HC-type zinc finger. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

DNmechanismADLOEUF 0.481 OMIM phenotype

Clinical Summary— KAT8

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Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.

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ClinVar Variants

11 unique Pathogenic / Likely Pathogenic· 123 VUS of 171 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — KAT8

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

0.48LOEUF

pLI 0.225

Z-score 3.49

OE 0.24 (0.13–0.48)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

3.15Z-score

OE missense 0.45 (0.39–0.53)

118 obs / 261.3 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.24 (0.13–0.48)

0≤0.351.4

Missense OE?0.45 (0.39–0.53)

0≤0.61.4

Synonymous OE?0.98

0≤1.21.6

LoF obs/exp: 6 / 24.7Missense obs/exp: 118 / 261.3Syn Z: 0.20

This gene — mechanism propensity

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 increa1

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

References

1.PMID 15923642 ↗

ClinVar Variant Classifications

171 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7

Likely Pathogenic4

VUS123

Likely Benign14

Benign3

Conflicting1

Pathogenic

Likely Pathogenic

123

VUS

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	7	0	0	7
Likely Pathogenic	0	4	0	0	4
VUS	14	105	3	1	123
Likely Benign	0	8	1	5	14
Benign	0	1	0	2	3
Conflicting	—				1
Total	14	125	4	8	152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

14 pathogenic / likely-pathogenic (of 21) ClinVar copy-number / structural variants overlap KAT8 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →