DOCK4

Chr 7

dedicator of cytokinesis 4

NCBI Gene: 9732 ENSG00000128512 UniProt: Q8N1I0 OMIM: 607679

The DOCK4 protein functions as a guanine nucleotide exchange factor that activates small GTPases and regulates adherens junctions between cells, playing a role in cell migration. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and autism spectrum features. The gene is highly constrained against loss-of-function variants (pLI=0.83, LOEUF=0.30), indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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)

—

P/LP submissions

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P/LP missense

0.30

LOEUF· LoF intol.

LOF

Mechanism· G2P