CDK5RAP2

Chr 9AR

CDK5 regulatory subunit associated protein 2

Also known as: C48, Cep215, MCPH3

NCBI Gene: 55755 ENSG00000136861 UniProt: Q96SN8 OMIM: 608201

The protein regulates CDK5 activity and localizes to the centrosome where it functions in centriole engagement and microtubule nucleation. Mutations cause primary microcephaly 3, an autosomal recessive disorder characterized by reduced brain size. The pathogenic mechanism involves dominant-negative effects that disrupt normal centrosome function and microtubule organization.

OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

This gene encodes a regulator of CDK5 (cyclin-dependent kinase 5) activity. The protein encoded by this gene is localized to the centrosome and Golgi complex, interacts with CDK5R1 and pericentrin (PCNT), plays a role in centriole engagement and microtubule nucleation, and has been linked to primary microcephaly and Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Microcephaly 3, primary, autosomal recessiveMIM #604804

Clinical highlights

Gene-disease validity (ClinGen)

autosomal recessive primary microcephaly · ARDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.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

0.66

LOEUF

LOF

Mechanism· G2P