USP5

Chr 12

ubiquitin specific peptidase 5

Also known as: ISOT

NCBI Gene: 8078 ENSG00000111667 UniProt: P45974

USP5 encodes a deubiquitinating enzyme that cleaves ubiquitin from target proteins and disassembles polyubiquitin chains, thereby regulating protein degradation and multiple cellular signaling pathways including Wnt, NF-kappa-B, autophagy, and immune responses. Mutations cause autosomal recessive neurodevelopmental disorder with developmental delay, intellectual disability, and behavioral abnormalities. The gene is highly constrained against loss-of-function variants, indicating that complete loss of USP5 function is likely detrimental to normal development.

ResearchSummary from RefSeq, UniProt

Ubiquitin (see MIM 191339)-dependent proteolysis is a complex pathway of protein metabolism implicated in such diverse cellular functions as maintenance of chromatin structure, receptor function, and degradation of abnormal proteins. A late step of the process involves disassembly of the polyubiquitin chains on degraded proteins into ubiquitin monomers. USP5 disassembles branched polyubiquitin chains by a sequential exo mechanism, starting at the proximal end of the chain (Wilkinson et al., 1995 [PubMed 7578059]).[supplied by OMIM, Mar 2010]

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

0.32

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)

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