HDAC8

Chr XXLD

histone deacetylase 8

Also known as: CDA07, CDLS5, HD8, HDACL1, KDAC8, MRXS6, RPD3, WTS

NCBI Gene: 55869 ENSG00000147099 UniProt: Q9BY41 OMIM: 300269

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

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 I of the histone deacetylase family. It catalyzes the deacetylation of lysine residues in the histone N-terminal tails and represses transcription in large multiprotein complexes with transcriptional co-repressors. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Cornelia de Lange syndrome 5MIM #300882

XLD

Clinical highlights

Gene-disease validity (ClinGen)

Cornelia de Lange syndrome · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

110

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· G2P

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