KAT5

Chr 11

lysine acetyltransferase 5

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

NCBI Gene: 10524 ENSG00000172977 UniProt: Q92993

This gene encodes a histone acetyltransferase that catalyzes acetylation of histones H2A and H4 to regulate gene transcription and plays critical roles in DNA repair, cell cycle progression, and chromatin remodeling. Mutations cause neurodevelopmental disorder with dysmorphic facies, sleep disturbance, and brain abnormalities with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.472), indicating that even single functional copies are critical for normal development.

ResearchSummary from RefSeq, OMIM, UniProt

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]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

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

Clinical highlights

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.47

LOEUF

—

Mechanism

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Missense constrained — critical functional residues

LoF Constraint?

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?

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?

LoF OE?0.26 (0.15–0.47)

0≤0.351.4

Missense OE?0.44 (0.39–0.51)

0≤0.61.4

Synonymous OE?1.19

0≤1.21.6

LoF obs/exp: 8 / 30.6Missense obs/exp: 146 / 330.9Syn Z: -1.78

Background carrier burden — how many people carry a rare variant somewhere in KAT5?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 240

538 rare PASS variants

Rare truncating (LoF)

1 in 470

83 rare PASS variants

Rare synonymous (reference)

1 in 130

399 rare PASS variants

Rare missense and truncating variants are carried at similar rates in KAT5; this gene does not show strong loss-of-function constraint by this measure. 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 180	1 in 4,700
South Asian	~43k	1 in 210	1 in 1,600
Remaining (unassigned)	~30k	1 in 190	1 in 920
European (Finnish)	~27k	1 in 660	1 in 2,000
Admixed American	~22k	1 in 210	1 in 1,900
African / African American	~21k	1 in 150	1 in 1,600
East Asian	~20k	1 in 140	≈ 1 in 9,300
Ashkenazi Jewish	~13k	1 in 720	1 in 810
Middle Eastern	~2,884	1 in 150	≈ 1 in 2,900

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): All 13 coding exons well covered in gnomAD exomes and genomes.? see exons ↓