USP15

Chr 12

ubiquitin specific peptidase 15

Also known as: UNPH-2, UNPH4

NCBI Gene: 9958ENSG00000135655UniProt: Q9Y4E8

This gene encodes a member of the ubiquitin specific protease (USP) family of deubiquitinating enzymes. USP enzymes play critical roles in ubiquitin-dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin-substrate bonds. The encoded protein associates with the COP9 signalosome, and also plays a role in transforming growth factor beta signalling through deubiquitination of receptor-activated SMAD transcription factors. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 2. [provided by RefSeq, Nov 2011]

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.
0
Active trials
61
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.21
LOEUF· LoF intol.
LOF
Mechanism· predicted
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?
0.21LOEUF
pLI 1.000
Z-score 6.20
OE 0.11 (0.06–0.21)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
3.50Z-score
OE missense 0.56 (0.50–0.61)
275 obs / 493.8 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?
LoF OE?0.11 (0.06–0.21)
0≤0.351.4
Missense OE?0.56 (0.50–0.61)
0≤0.61.4
Synonymous OE?0.88
0≤1.21.6
LoF obs/exp: 6 / 56.2Missense obs/exp: 275 / 493.8Syn Z: 1.24

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

USP15 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients