KAT5

Chr 11AD

lysine acetyltransferase 5

Also known as: ESA1, HTATIP, HTATIP1, NEDFASB, PLIP, TIP, TIP60, ZC2HC5

NCBI Gene: 10524ENSG00000172977UniProt: Q92993

The protein encoded by this gene belongs to the MYST family of histone acetyl transferases (HATs) and was originally isolated as an HIV-1 TAT-interactive protein. HATs play important roles in regulating chromatin remodeling, transcription and other nuclear processes by acetylating histone and nonhistone proteins. This protein is a histone acetylase that has a role in DNA repair and apoptosis and is thought to play an important role in signal transduction. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalitiesMIM #619103
AD
0
ClinVar variants
0
Pathogenic / LP
0.09
pLI score
0
Active trials
Clinical Summary— KAT5
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

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.
0.47LOEUF
pLI 0.088
Z-score 3.78
OE 0.26 (0.15–0.47)
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.
3.61Z-score
OE missense 0.44 (0.39–0.51)
146 obs / 330.9 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.0.26 (0.15–0.47)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.44 (0.39–0.51)
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.1.19
0≤1.21.6
LoF obs/exp: 8 / 30.6Missense obs/exp: 146 / 330.9Syn Z: -1.78

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

KAT5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

KAT5-related neurodevelopmental syndrome

strong
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities

MIM #619103

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
KAT5 promotes invasion and metastasis through C-MYC stabilization in ATC.
Wei X et al.·Endocr Relat Cancer
2019
Jatrorrhizine Alleviates Calcific Aortic Valve Disease via Interfering With Glycolysis Targeting ALDOA K42 Lactylation.
Wu J et al.·Phytother Res
2025
LOXL2 reduces susceptibility to PARP inhibitors by promoting super-enhancer-regulated DNA damage repair in high-grade serous ovarian cancer.
Song C et al.·Oncogene
2025
Quantifying Tip60 (Kat5) stratifies breast cancer.
McGuire A et al.·Sci Rep
2019
Identification of epigenetic regulators of fibrotic transformation in cardiac fibroblasts through bulk and single-cell CRISPR screens.
Aguado-Alvaro LP et al.·Nat Commun
2025
Depletion of TRRAP Induces p53-Independent Senescence in Liver Cancer by Down-Regulating Mitotic Genes.
Kwan SY et al.·Hepatology
2020
KAT5 and KAT6B are in positive regulation on cell proliferation of prostate cancer through PI3K-AKT signaling.
He W et al.·Int J Clin Exp Pathol
2013
Functions of TIP60/NuA4 Complex Subunits in Cell Differentiation.
Hashemi F et al.·Cells
2025Review
De Novo KAT5 Variants Cause a Syndrome with Recognizable Facial Dysmorphisms, Cerebellar Atrophy, Sleep Disturbance, and Epilepsy.
Humbert J et al.·Am J Hum Genet
2020
Antisense transcription regulates the expression of sense gene via alternative polyadenylation.
Shen T et al.·Protein Cell
2018
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