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…

LOEUF 0.47

Clinical Summary— KAT5

⚡

Population Constraint (gnomAD)

Constrained for loss-of-function variants (OE-LoF 0.26) despite low pLI — interpret in context.

📋

ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 114 VUS of 163 total submissions

Explore recent and relevant literature in Research Assistant →

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

ClinVar Variant Classifications

163 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic1

VUS114

Likely Benign18

Benign9

Conflicting4

Pathogenic

Likely Pathogenic

114

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	3	0	0	3
Likely Pathogenic	0	1	0	0	1
VUS	6	77	28	3	114
Likely Benign	1	1	9	7	18
Benign	0	0	8	1	9
Conflicting	—				4
Total	7	82	45	11	149

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

View in ClinVar →

10 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap KAT5 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →