CDC42

Chr 1

cell division cycle 42

Also known as: CDC42Hs, G25K, TKS

NCBI Gene: 998 ENSG00000070831 UniProt: P60953

CDC42 encodes a small GTPase that regulates actin cytoskeleton dynamics, cell migration, and neuronal processes including dendritic spine formation and filopodia extension. Mutations cause Takenouchi-Kosaki syndrome, a neurodevelopmental disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (LOEUF 0.501), reflecting its essential role in cellular functions.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a small GTPase of the Rho-subfamily, which regulates signaling pathways that control diverse cellular functions including cell morphology, migration, endocytosis and cell cycle progression. This protein is highly similar to Saccharomyces cerevisiae Cdc 42, and is able to complement the yeast cdc42-1 mutant. The product of oncogene Dbl was reported to specifically catalyze the dissociation of GDP from this protein. This protein could regulate actin polymerization through its direct binding to Neural Wiskott-Aldrich syndrome protein (N-WASP), which subsequently activates Arp2/3 complex. Alternative splicing of this gene results in multiple transcript variants. Pseudogenes of this gene have been identified on chromosomes 3, 4, 5, 7, 8 and 20. [provided by RefSeq, Apr 2013]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtTakenouchi-Kosaki syndrome

Clinical highlights

Gene-disease validity (ClinGen)

macrothrombocytopenia-lymphedema-developmental delay-facial dysmorphism-camptodactyly syndrome · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

421

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.50

LOEUF

Multiple*

Mechanism· predicted

📖