HDAC4

Chr 2AD

histone deacetylase 4

Also known as: AHO3, BDMR, HA6116, HD4, HDAC-4, HDAC-A, HDACA, NEDCHF

NCBI Gene: 9759ENSG00000068024UniProt: P56524OMIM: 605314

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It possesses histone deacetylase activity and represses transcription when tethered to a promoter. This protein does not bind DNA directly, but through transcription factors MEF2C and MEF2D. It seems to interact in a multiprotein complex with RbAp48 and HDAC3. [provided by RefSeq, Jul 2008]

GeneReviewsOMIMResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with central hypotonia and dysmorphic faciesMIM #619797
AD

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.
2
Active trials
179
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.05
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
📖
GeneReview available — HDAC4
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.05LOEUF
pLI 1.000
Z-score 7.02
OE 0.00 (0.00–0.05)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?
2.93Z-score
OE missense 0.69 (0.64–0.75)
497 obs / 717.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.00 (0.00–0.05)
0≤0.351.4
Missense OE?0.69 (0.64–0.75)
0≤0.61.4
Synonymous OE?1.19
0≤1.21.6
LoF obs/exp: 0 / 57.4Missense obs/exp: 497 / 717.6Syn Z: -2.67

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HDAC4 · protein map & ClinVar variants

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

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients