USP14

Chr 18

ubiquitin specific peptidase 14

Also known as: TGT, Ubp6

NCBI Gene: 9097 ENSG00000101557 UniProt: P54578

This deubiquitinase enzyme removes ubiquitin from proteasome-targeted proteins and regulates protein degradation pathways essential for synaptic function. Mutations cause autosomal recessive neurodevelopmental disorders with early-onset developmental delay, ataxia, and intellectual disability. The gene is highly constrained against loss-of-function variants (pLI 0.91), reflecting its critical role in neuronal development and synaptic transmission.

ResearchSummary from RefSeq, UniProt

This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. Mice with a mutation that results in reduced expression of the ortholog of this protein are retarded for growth, develop severe tremors by 2 to 3 weeks of age followed by hindlimb paralysis and death by 6 to 10 weeks of age. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

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.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

107

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.35

LOEUF· LoF intol.

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Mechanism

Some data sources returned errors (1)