HDAC2

Chr 6

histone deacetylase 2

Also known as: HD2, KDAC2, RPD3, YAF1

NCBI Gene: 3066 ENSG00000196591 UniProt: Q92769

HDAC2 encodes a histone deacetylase that removes acetyl groups from core histones H2A, H2B, H3, and H4, leading to transcriptional repression and regulation of cell cycle progression and developmental events. Heterozygous loss-of-function mutations cause a neurodevelopmental disorder with intellectual disability and developmental delay through an autosomal dominant inheritance pattern. The pathogenic mechanism involves haploinsufficiency, as HDAC2 is highly intolerant to loss-of-function variants.

ResearchSummary from RefSeq, UniProt, Mechanism

This gene product belongs to the histone deacetylase family. Histone deacetylases act via the formation of large multiprotein complexes, and are responsible for the deacetylation of lysine residues at the N-terminal regions of core histones (H2A, H2B, H3 and H4). This protein forms transcriptional repressor complexes by associating with many different proteins, including YY1, a mammalian zinc-finger transcription factor. Thus, it plays an important role in transcriptional regulation, cell cycle progression and developmental events. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2010]

ResearchGenerating clinical summary…

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.Based on population constraint only.

Active trials

320

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.10

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

0.10LOEUF

pLI 1.000

Z-score 5.05

OE 0.00 (0.00–0.10)

Highly constrained

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

Missense Constraint?

4.05Z-score

OE missense 0.30 (0.25–0.36)

79 obs / 264.4 exp

Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?

LoF OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.30 (0.25–0.36)

0≤0.61.4

Synonymous OE?0.82

0≤1.21.6

LoF obs/exp: 0 / 29.7Missense obs/exp: 79 / 264.4Syn Z: 1.28

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HDAC2 · 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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Prostate Cancer Metastatic Castration-ResistantAbnormal DNA RepairMetastatic Prostate Carcinoma

Abiraterone/Prednisone, Olaparib, or Abiraterone/Prednisone + Olaparib in Patients With Metastatic Castration-Resistant Prostate Cancer With DNA Repair Defects

ACTIVE NOT RECRUITING

NCT03012321Phase PHASE2Northwestern UniversityStarted 2017-01-12

OlaparibAbiraterone AcetatePrednisone

Clinical Literature

Open Research Assistant →

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3

PubTator3

Histone deacetylase-2: A potential regulator and therapeutic target in liver disease (Review)

Liu YR et al.·Int J Mol Med

2021Review