USP5
Chr 12ubiquitin specific peptidase 5
Also known as: ISOT
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.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Highly missense-constrained (top ~0.1%)
ClinVar Variant Classifications
154 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 43 | 0 | 43 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 70 | 13 | 0 | 83 |
Likely Benign | 0 | 1 | 0 | 1 | 2 |
Benign | 0 | 0 | 0 | 5 | 5 |
| Total | 0 | 71 | 58 | 6 | 135 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
USP5 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools