PRR5

Chr 22

proline rich 5

Also known as: FLJ20185k, PP610, PROTOR-1, PROTOR1

NCBI Gene: 55615 ENSG00000186654 UniProt: P85299 OMIM: 609406

The protein is an associated subunit of mTORC2, which regulates cell growth and survival in response to hormonal signals and controls actin cytoskeleton organization upstream of Rho GTPases. Mutations in this gene cause autosomal recessive intellectual disability with microcephaly, seizures, and brain malformations including cortical dysplasia. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.635), and affected individuals typically present in infancy with developmental delays and neurological symptoms.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a protein with a proline-rich domain. This gene is located in a region of chromosome 22 reported to contain a tumor suppressor gene that may be involved in breast and colorectal tumorigenesis. The protein is a component of the mammalian target of rapamycin complex 2 (mTORC2), and it regulates platelet-derived growth factor (PDGF) receptor beta expression and PDGF signaling to Akt and S6K1. Alternative splicing and the use of alternative promoters results in transcripts encoding different isoforms. Read-through transcripts from this gene into the downstream Rho GTPase activating protein 8 (ARHGAP8) gene also exist, which led to the original description of PRR5 and ARHGAP8 being a single gene. [provided by RefSeq, Nov 2010]

OMIM ResearchGenerating clinical summary…

Clinical highlights

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.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.64

LOEUF

Multiple*

Mechanism· predicted