PAK3

Chr XXLR

p21 (RAC1) activated kinase 3

Also known as: ARA, MRX30, MRX47, OPHN3, PAK-3, PAK3beta, XLID30, bPAK

NCBI Gene: 5063 ENSG00000077264 UniProt: O75914 OMIM: 300142

PAK3 encodes a serine/threonine kinase that regulates cytoskeletal reorganization, dendritic spine morphogenesis, and synaptic plasticity by acting downstream of CDC42 and RAC1. Mutations cause X-linked intellectual developmental disorder with inheritance following an X-linked recessive pattern. The gene is highly constrained against loss-of-function variants, indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

The protein encoded by this gene is a serine-threonine kinase and forms an activated complex with GTP-bound RAS-like (P21), CDC2 and RAC1. This protein may be necessary for dendritic development and for the rapid cytoskeletal reorganization in dendritic spines associated with synaptic plasticity. Defects in this gene are the cause of a non-syndromic form of X-linked intellectual disability. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2017]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Intellectual developmental disorder, X-linked 30MIM #300558

XLR

Clinical highlights

Gene-disease validity (ClinGen)

X-linked complex neurodevelopmental disorder · XLDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.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

0.29

LOEUF· LoF intol.

Multiple*

Mechanism· G2P