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.

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]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Li-Ghorgani-Weisz-Hubshman syndromeMIM #618974

UniProtLi-Ghorbani-Weisz-Hubshman syndrome

Clinical highlights

Gene–disease validity

Not independently assessedOMIM lists Li-Ghorgani-Weisz-Hubshman syndrome; no ClinGen or GenCC tier

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.48

LOEUF

Mechanism· predicted

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

Background carrier burden — how many people carry a rare variant somewhere in KAT8?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 210

460 rare PASS variants

Rare truncating (LoF)

1 in 3,100

89 rare PASS variants

Rare synonymous (reference)

1 in 150

308 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for KAT8. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 230	1 in 3,200
South Asian	~43k	1 in 140	≈ 1 in 8,600
Remaining (unassigned)	~30k	1 in 160	≈ 1 in 15,000
European (Finnish)	~27k	1 in 400	1 in 4,000
Admixed American	~22k	1 in 220	1 in 900
African / African American	~21k	1 in 170	1 in 1,200
East Asian	~20k	1 in 270	≈ 1 in 4,900
Ashkenazi Jewish	~13k	1 in 1,900	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 260	≈ 1 in 2,600

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 10 of 11 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 11.? see exons ↓