USP33

Chr 1

ubiquitin specific peptidase 33

Also known as: VDU1

NCBI Gene: 23032 ENSG00000077254 UniProt: Q8TEY7 OMIM: 615146

This gene encodes a deubiquitinating enzyme that regulates centrosome duplication, axon guidance signaling through ROBO1, and G-protein coupled receptor recycling. Mutations cause autosomal dominant neurodevelopmental disorder with developmental delay, intellectual disability, and autism spectrum disorder. The gene is highly constrained against loss-of-function variants (pLI = 0.86, LOEUF = 0.33), indicating that complete loss of protein function is likely not tolerated.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a deubiquinating enzyme important in a variety of processes, including Slit-dependent cell migration and beta-2 adrenergic receptor signaling. The protein is negatively regulated through ubiquitination by von Hippel-Lindau tumor protein (VHL). Alternative splicing results in multiple transcript variants and protein isoforms. [provided by RefSeq, Jun 2012]

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

0.33

LOEUF· LoF intol.

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Mechanism