WWP1

Chr 8

WW domain containing E3 ubiquitin protein ligase 1

Also known as: AIP5, Tiul1, hSDRP1

NCBI Gene: 11059 ENSG00000123124 UniProt: Q9H0M0 OMIM: 602307

The protein functions as an E3 ubiquitin ligase that targets multiple substrates for proteasomal degradation and regulates key cellular pathways including TGF-beta signaling and the Hippo pathway involved in cell contact inhibition. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. This gene is highly constrained against loss-of-function variants in the population, indicating that such variants are likely to be pathogenic.

GeneReviews OMIM ResearchSummary from RefSeq, UniProt

WW domain-containing proteins are found in all eukaryotes and play an important role in the regulation of a wide variety of cellular functions such as protein degradation, transcription, and RNA splicing. This gene encodes a protein which contains 4 tandem WW domains and a HECT (homologous to the E6-associated protein carboxyl terminus) domain. The encoded protein belongs to a family of NEDD4-like proteins, which are E3 ubiquitin-ligase molecules and regulate key trafficking decisions, including targeting of proteins to proteosomes or lysosomes. Alternative splicing of this gene generates at least 6 transcript variants; however, the full length nature of these transcripts has not been defined. [provided by RefSeq, Jul 2008]

GeneReviews 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

0.25

LOEUF· LoF intol.

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Mechanism

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GeneReview available — WWP1