USP8
Chr 15ubiquitin specific peptidase 8
Also known as: HumORF8, PITA4, SPG59, UBPY
The protein functions as a deubiquitinating enzyme that removes ubiquitin from target proteins, regulating endosomal trafficking, cargo sorting, and cell cycle progression. Mutations cause pituitary adenoma 4 (ACTH-secreting), which follows a somatic inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI >0.99), suggesting that germline mutations would likely be severe.
Primary Disease Associations & Inheritance
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Mild missense constraint
ClinVar Variant Classifications
256 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 | 4 | 21 | 0 | 25 |
Likely Pathogenic | 0 | 0 | 0 | 0 | 0 |
VUS | 2 | 81 | 23 | 0 | 106 |
Likely Benign | 1 | 3 | 22 | 41 | 67 |
Benign | 0 | 12 | 8 | 6 | 26 |
Conflicting | — | 1 | |||
| Total | 3 | 100 | 74 | 47 | 225 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
USP8 · 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
External Resources
Links to major genomics databases and tools