STUB1

Chr 16ADAR

STIP1 homology and U-box containing protein 1

Also known as: CHIP, HSPABP2, NY-CO-7, SCA48, SCAR16, SDCCAG7, UBOX1

NCBI Gene: 10273ENSG00000103266UniProt: Q9UNE7

This gene encodes a protein containing tetratricopeptide repeat and a U-box that functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2. [provided by RefSeq, Jun 2014]

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 48MIM #618093
AD
Spinocerebellar ataxia, autosomal recessive 16MIM #615768
AR
341
ClinVar variants
93
Pathogenic / LP
0.02
pLI score
1
Active trials
Clinical Summary— STUB1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.34) despite low pLI — interpret in context.
📋
ClinVar Variants
93 Pathogenic / Likely Pathogenic· 140 VUS of 341 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.68LOEUF
pLI 0.019
Z-score 2.54
OE 0.34 (0.19–0.68)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.16Z-score
OE missense 0.76 (0.66–0.87)
143 obs / 187.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.34 (0.19–0.68)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.76 (0.66–0.87)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.40
0≤1.21.6
LoF obs/exp: 6 / 17.4Missense obs/exp: 143 / 187.9Syn Z: -2.79

ClinVar Variant Classifications

341 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic63
Likely Pathogenic30
VUS140
Likely Benign77
Benign21
Conflicting10
63
Pathogenic
30
Likely Pathogenic
140
VUS
77
Likely Benign
21
Benign
10
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
9
50
0
63
Likely Pathogenic
10
11
9
0
30
VUS
3
101
35
1
140
Likely Benign
0
3
32
42
77
Benign
0
0
21
0
21
Conflicting
—10
Total1712414743341

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Spinocerebellar ataxia 48

MIM #618093

Molecular basis of disorder known

Autosomal dominant

Spinocerebellar ataxia, autosomal recessive 16

MIM #615768

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
NGS in Hereditary Ataxia: When Rare Becomes Frequent.
Galatolo D et al.·Int J Mol Sci
2021
Autosomal dominant cerebellar ataxias: new genes and progress towards treatments.
Coarelli G et al.·Lancet Neurol
2023Review
Trehalose induces autophagy via lysosomal-mediated TFEB activation in models of motoneuron degeneration.
Rusmini P et al.·Autophagy
2019Functional
Xbp1s-FoxO1 axis governs lipid accumulation and contractile performance in heart failure with preserved ejection fraction.
Schiattarella GG et al.·Nat Commun
2021
DDX39B drives colorectal cancer progression by promoting the stability and nuclear translocation of PKM2.
Zhao G et al.·Signal Transduct Target Ther
2022
STUB1/CHIP: New insights in cancer and immunity.
Liu Y et al.·Biomed Pharmacother
2023Review
The UBA1-STUB1 Axis Mediates Cancer Immune Escape and Resistance to Checkpoint Blockade.
Bao Y et al.·Cancer Discov
2025
BAG2 Inhibits Cervical Cancer Progression by Modulating Type I Interferon Signaling through Stabilizing STING.
Yao S et al.·Adv Sci (Weinh)
2025
Extreme phenotypic heterogeneity in non-expansion spinocerebellar ataxias.
Cunha P et al.·Am J Hum Genet
2023
Clinical and functional characterization of a novel STUB1 mutation in a Chinese spinocerebellar ataxia 48 pedigree.
Li J et al.·Orphanet J Rare Dis
2024Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Bisphosphate nucleotidase 1 promotes progression and docetaxel resistance in triple-negative breast cancer via STUB1-mediated destabilization of LIMA1.
Ling YX et al.·Cell Death Dis
2026🔓 Open Access
STUB1-mediated PGC-1α ubiquitination promotes postoperative cognitive dysfunction in aged mice via modulating autophagy-lysosome machinery.
Shen QH et al.·Eur J Med Res
2025🔓 Open Access
UBE2K promotes breast cancer growth by ubiquitinating and degrading STUB1 to regulate the PKA/CREB1 signaling pathway, forming a feedback loop.
Mou J et al.·Biochim Biophys Acta Mol Basis Dis
2026
Hypoxia-activated HSP90AA1/STUB1 axis promotes acute pancreatitis via necroptosis protein stabilization.
Song TJ et al.·Life Sci
2026
ARCN1 suppresses innate immune responses against respiratory syncytial virus by promoting STUB1-mediated IKKε degradation.
Cai J et al.·PLoS Pathog
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Rare DisordersUndiagnosed DisordersDisorders of Unknown Prevalence

Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford

RECRUITING
NCT01793168Sanford HealthStarted 2010-07

External Resources

Links to major genomics databases and tools