HDAC6

Chr XXLD

histone deacetylase 6

Also known as: CPBHM, HD6, JM21, KDAC6, PPP1R90

NCBI Gene: 10013ENSG00000094631UniProt: Q9UBN7OMIM: 300272

HDAC6 encodes a histone deacetylase that deacetylates tubulin and other non-histone substrates, playing critical roles in microtubule dynamics, autophagy, and misfolded protein clearance. Mutations cause chondrodysplasia with platyspondyly, distinctive brachydactyly, hydrocephaly, and microphthalmia with X-linked dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating that HDAC6 function is essential for normal development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismXLDLOEUF 0.071 OMIM phenotype
Clinical Summary— HDAC6
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
32 unique Pathogenic / Likely Pathogenic· 101 VUS of 300 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.07LOEUF
pLI 1.000
Z-score 5.95
OE 0.00 (0.00–0.07)
Highly constrained

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

Missense Constraint
3.29Z-score
OE missense 0.58 (0.53–0.64)
285 obs / 490.0 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.07)
0≤0.351.4
Missense OE0.58 (0.53–0.64)
0≤0.61.4
Synonymous OE0.97
0≤1.21.6
LoF obs/exp: 0 / 41.2Missense obs/exp: 285 / 490.0Syn Z: 0.34
DN
0.3196th %ile
GOF
0.3986th %ile
LOF
0.71top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.07

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

300 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic30
Likely Pathogenic2
VUS101
Likely Benign32
Benign6
Conflicting4
30
Pathogenic
2
Likely Pathogenic
101
VUS
32
Likely Benign
6
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
29
0
30
Likely Pathogenic
0
1
1
0
2
VUS
0
94
7
0
101
Likely Benign
1
17
3
11
32
Benign
0
1
1
4
6
Conflicting
—4
Total21134115175

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

View in ClinVar →

Protein Context — Lollipop Plot

HDAC6 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

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