STUB1
Chr 16ADARSTIP1 homology and U-box containing protein 1
Also known as: CHIP, HSPABP2, NY-CO-7, SCA48, SCAR16, SDCCAG7, UBOX1
The STUB1 protein functions as an E3 ubiquitin ligase and cochaperone that targets misfolded proteins for proteasomal degradation and maintains mitochondrial quality control. Mutations cause spinocerebellar ataxia with both autosomal recessive (SCA16) and autosomal dominant (SCA48) inheritance patterns. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.68), and the ataxias primarily affect the cerebellum and result in progressive movement disorders.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). The Badonyi & Marsh model scores gain-of-function highest among its predictions, but genomic evidence (constraint, ClinVar variant spectrum, and literature) most strongly supports dominant-negative. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
262 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 | 6 | 9 | 46 | 0 | 61 |
Likely Pathogenic | 16 | 10 | 1 | 0 | 27 |
VUS | 3 | 59 | 23 | 1 | 86 |
Likely Benign | 0 | 3 | 24 | 31 | 58 |
Benign | 0 | 0 | 21 | 0 | 21 |
Conflicting | — | 9 | |||
| Total | 25 | 81 | 115 | 32 | 262 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
STUB1 · 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
External Resources
Links to major genomics databases and tools