OTUB1

Chr 11

OTU deubiquitinase, ubiquitin aldehyde binding 1

Also known as: HSPC263, OTB1, OTU1

NCBI Gene: 55611ENSG00000167770UniProt: Q96FW1

The product of this gene is a member of the OTU (ovarian tumor) superfamily of predicted cysteine proteases. The encoded protein is a highly specific ubiquitin iso-peptidase, and cleaves ubiquitin from branched poly-ubiquitin chains but not from ubiquitinated substrates. It interacts with another ubiquitin protease and an E3 ubiquitin ligase that inhibits cytokine gene transcription in the immune system. It is proposed to function in specific ubiquitin-dependent pathways, possibly by providing an editing function for polyubiquitin chain growth. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2008]

39
ClinVar variants
9
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— OTUB1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
9 Pathogenic / Likely Pathogenic· 29 VUS of 39 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.31LOEUF
pLI 0.971
Z-score 3.39
OE 0.07 (0.02–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

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.
2.20Z-score
OE missense 0.52 (0.43–0.62)
85 obs / 164.1 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

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.0.07 (0.02–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.43–0.62)
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.1.06
0≤1.21.6
LoF obs/exp: 1 / 15.4Missense obs/exp: 85 / 164.1Syn Z: -0.38

ClinVar Variant Classifications

39 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic3
VUS29
Likely Benign1
6
Pathogenic
3
Likely Pathogenic
29
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
3
0
3
VUS
0
27
2
0
29
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total02711139

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

OTUB1 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Deubiquitinating enzyme OTUB1 promotes cancer cell immunosuppression via preventing ER-associated degradation of immune checkpoint protein PD-L1.
Zhu D et al.·Cell Death Differ
2021
OTUB1 suppresses Hippo signaling via modulating YAP protein in gastric cancer.
Yan C et al.·Oncogene
2022
Target deubiquitinase OTUB1 as a therapeatic strategy for BLCA via β-catenin/necroptosis signal pathway.
Liao Y et al.·Int J Biol Sci
2024
CircSEC24B activates autophagy and induces chemoresistance of colorectal cancer via OTUB1-mediated deubiquitination of SRPX2.
Wang D et al.·Cell Death Dis
2024
OTUB1 promotes the progression of acute myeloid leukemia by regulating glycolysis via deubiquitinating c-Myc.
Liao Y et al.·Cell Signal
2025
The deubiquitylase OTUB1 drives gemcitabine resistance in pancreatic cancer by enhancing pyrimidine metabolism through modulating DHODH mRNA stability.
Zhang W et al.·Cell Death Dis
2025
Expression of OTUB1 in hepatocellular carcinoma and its effects on HCC cell migration and invasion.
Ni Q et al.·Acta Biochim Biophys Sin (Shanghai)
2017
The deubiquitinase OTUB1 fosters papillary thyroid carcinoma growth through EYA1 stabilization.
Xie P et al.·J Cell Mol Med
2021
Hypoxia-elicited exosomal HIF-1α promotes drug resistance of melanoma through modulating SLC7A11 ubiquitination.
Chen J et al.·Cell Signal
2025
A biomimetic senotherapy replenishing MAT2A promotes wound regeneration in preclinical models.
Lv D et al.·Nat Commun
2025Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools