DOCK3

Chr 3

dedicator of cytokinesis 3

Also known as: MOCA, NEDIDHA, PBP

NCBI Gene: 1795 ENSG00000088538 UniProt: Q8IZD9

DOCK3 encodes a guanine nucleotide exchange factor that activates Rac1 and induces axonal outgrowth in the central nervous system through stimulation of the WAVE complex. Biallelic mutations cause autosomal recessive neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia. The gene is highly constrained against loss-of-function variants (pLI >0.99, LOEUF 0.158), indicating that functional copies are critical for normal development.

ResearchSummary from RefSeq, OMIM, UniProt

This gene is specifically expressed in the central nervous system (CNS). It encodes a member of the DOCK (dedicator of cytokinesis) family of guanine nucleotide exchange factors (GEFs). This protein, dedicator of cytokinesis 3 (DOCK3), is also known as modifier of cell adhesion (MOCA) and presenilin-binding protein (PBP). The DOCK3 and DOCK1, -2 and -4 share several conserved amino acids in their DHR-2 (DOCK homology region 2) domains that are required for GEF activity, and bind directly to WAVE proteins [Wiskott-Aldrich syndrome protein (WASP) family Verprolin-homologous proteins] via their DHR-1 domains. The DOCK3 induces axonal outgrowth in CNS by stimulating membrane recruitment of the WAVE complex and activating the small G protein Rac1. This gene is associated with an attention deficit hyperactivity disorder-like phenotype by a complex chromosomal rearrangement. [provided by RefSeq, Aug 2010]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtNeurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia

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

0.16

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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