CHD4

Chr 12AD

chromodomain helicase DNA binding protein 4

Also known as: CHD-4, Mi-2b, Mi2-BETA, SIHIWES

NCBI Gene: 1108 ENSG00000111642 UniProt: Q14839 OMIM: 603277

CHD4 encodes an ATP-dependent chromatin-remodeling factor that binds and distorts nucleosomal DNA as a component of the histone deacetylase NuRD complex, participating in chromatin remodeling, transcriptional repression, and DNA repair. Loss-of-function mutations cause Sifrim-Hitz-Weiss syndrome, inherited in an autosomal dominant pattern. The protein is involved in neurogenesis and localizes to damaged chromatin to promote double-strand break repair.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

The product of this gene belongs to the SNF2/RAD54 helicase family. It represents the main component of the nucleosome remodeling and deacetylase complex and plays an important role in epigenetic transcriptional repression. Patients with dermatomyositis develop antibodies against this protein. Somatic mutations in this gene are associated with serous endometrial tumors. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2014]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Sifrim-Hitz-Weiss syndromeMIM #617159

Clinical highlights

Gene-disease validity (ClinGen)

syndromic intellectual disability · ADDefinitivesufficient 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

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.16

LOEUF· LoF intol.

LOF

Mechanism· G2P