USP12
Chr 13ubiquitin specific peptidase 12
Also known as: UBH1, USP12L1
USP12 encodes a deubiquitinating enzyme that regulates immune signaling pathways including NF-kappa-B and interferon responses, T-cell receptor signaling, and NOTCH signaling, and also protects neurons against polyglutamine expansion-mediated neurodegeneration. Mutations cause autosomal dominant neurodevelopmental disorder with seizures and brain abnormalities. The gene is highly constrained against loss-of-function variants (pLI 0.97), indicating that such variants are likely to cause severe phenotypes.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
72 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 | 29 | 0 | 29 |
Likely Pathogenic | 0 | 0 | 2 | 0 | 2 |
VUS | 0 | 24 | 3 | 0 | 27 |
Likely Benign | 0 | 0 | 0 | 1 | 1 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 24 | 35 | 1 | 60 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
USP12 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
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