HDAC8

Chr XXLD

histone deacetylase 8

This histone deacetylase catalyzes the deacetylation of lysine residues in histone N-terminal tails, repressing transcription in large multiprotein complexes. Loss-of-function mutations cause Cornelia de Lange syndrome 5, inherited in an X-linked dominant pattern. The high constraint scores (pLI 0.98, LOEUF 0.30) indicate the gene is highly intolerant to loss-of-function variants.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLDLOEUF 0.301 OMIM phenotype
Clinical SummaryHDAC8
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Gene-Disease Validity (ClinGen)
Cornelia de Lange syndrome · XLDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.977
Z-score 3.47
OE 0.06 (0.020.30)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.82Z-score
OE missense 0.35 (0.280.44)
51 obs / 147.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.06 (0.020.30)
00.351.4
Missense OE0.35 (0.280.44)
00.61.4
Synonymous OE0.94
01.21.6
LoF obs/exp: 1 / 16.0Missense obs/exp: 51 / 147.4Syn Z: 0.34
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveHDAC8-related Cornelia de Lange syndromeLOFXLR
definitiveHDAC8-related Cornelia de Lange syndromeLOFmonoallelic_X_heterozygous
DN
0.3495th %ile
GOF
0.3491th %ile
LOF
0.66top 25%

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

LOFprediction above median · LOEUF 0.30

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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

HDAC8 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
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