KAT8

Chr 16AD

lysine acetyltransferase 8

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

NCBI Gene: 84148ENSG00000103510UniProt: Q9H7Z6

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]

Primary Disease Associations & Inheritance

Li-Ghorgani-Weisz-Hubshman syndromeMIM #618974
AD
UniProtLi-Ghorbani-Weisz-Hubshman syndrome
169
ClinVar variants
25
Pathogenic / LP
0.22
pLI score
0
Active trials
Clinical Summary— KAT8
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.24) despite low pLI — interpret in context.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 128 VUS of 169 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Missense constrained — critical functional residues
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
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?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
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?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.24 (0.13–0.48)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.45 (0.39–0.53)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.98
0≤1.21.6
LoF obs/exp: 6 / 24.7Missense obs/exp: 118 / 261.3Syn Z: 0.20

ClinVar Variant Classifications

169 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic7
VUS128
Likely Benign12
Benign3
Conflicting1
18
Pathogenic
7
Likely Pathogenic
128
VUS
12
Likely Benign
3
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
7
11
0
18
Likely Pathogenic
0
4
3
0
7
VUS
10
102
15
1
128
Likely Benign
0
7
1
4
12
Benign
0
1
0
2
3
Conflicting
—1
Total10121307169

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

View 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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Li-Ghorgani-Weisz-Hubshman syndrome

MIM #618974

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — KAT8
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KAT8-mediated H4K16ac is essential for sustaining trophoblast self-renewal and proliferation via regulating CDX2.
Bi S et al.·Nat Commun
2024
Targeting KAT8 alleviates self-RNA-driven skin inflammation by modulating histone H4 lysine 16 acetylation in psoriasis.
Xiang Y et al.·Cell Death Differ
2026
CHI-KAT8i5 suppresses ESCC tumor growth by inhibiting KAT8-mediated c-Myc stability.
Zhang D et al.·Cell Rep
2025
Shared genetic risk loci between Alzheimer's disease and related dementias, Parkinson's disease, and amyotrophic lateral sclerosis.
Wainberg M et al.·Alzheimers Res Ther
2023
An integrative framework to prioritize genes in more than 500 loci associated with body mass index.
Hemerich D et al.·Am J Hum Genet
2024
The role of histone acetyltransferases in tumorigenesis and their therapeutic potential: A review.
Lin R et al.·Biochem Biophys Res Commun
2026Review
Routine Diagnostics Confirm Novel Neurodevelopmental Disorders.
Jauss RT et al.·Genes (Basel)
2022
Histone Acetyltransferase MOF-Mediated AURKB K215 Acetylation Drives Breast Cancer Cell Proliferation via c-MYC Stabilization.
Miao Y et al.·Cells
2025
Variation in VKORC1 Is Associated with Vascular Dementia.
Mur J et al.·J Alzheimers Dis
2021
22q11.2 deletion carriers and schizophrenia-associated novel variants.
Balan S et al.·Br J Psychiatry
2014
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools