OTUD6B

Chr 8AR

OTU deubiquitinase 6B

Also known as: CGI-77, DUBA-5, DUBA5, IDDFSDA

NCBI Gene: 51633ENSG00000155100UniProt: Q8N6M0

This gene encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Deubiquitinating enzymes are primarily involved in removing ubiquitin from proteins targeted for degradation. This protein may function as a negative regulator of the cell cycle in B cells. [provided by RefSeq, Nov 2013]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomaliesMIM #617452
AR
0
Active trials
54
Pathogenic / LP
142
ClinVar variants
13
Pubs (1 yr)
0.3
Missense Z
1.32
LOEUF
Clinical Summary— OTUD6B
🧬
Gene-Disease Validity (ClinGen)
syndromic intellectual disability · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
54 Pathogenic / Likely Pathogenic· 68 VUS of 142 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.32LOEUF
pLI 0.000
Z-score 0.65
OE 0.82 (0.52–1.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.30Z-score
OE missense 0.93 (0.81–1.07)
145 obs / 155.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.82 (0.52–1.32)
0≤0.351.4
Missense OE0.93 (0.81–1.07)
0≤0.61.4
Synonymous OE1.01
0≤1.21.6
LoF obs/exp: 12 / 14.7Missense obs/exp: 145 / 155.4Syn Z: -0.05
DN
DN
0.7131th %ile
GOF
0.5366th %ile
LOF
0.2484th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

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.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

142 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
Likely Pathogenic8
VUS68
Likely Benign11
Benign4
Conflicting5
46
Pathogenic
8
Likely Pathogenic
68
VUS
11
Likely Benign
4
Benign
5
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
0
38
0
46
Likely Pathogenic
2
4
2
0
8
VUS
1
49
17
1
68
Likely Benign
0
1
4
6
11
Benign
0
1
2
1
4
Conflicting
—5
Total1155638142

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

View in ClinVar →

OTUD6B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

OTUD6B-related intellectual disability syndrome associated with seizures and dysmorphic features

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Proximity proteomics reveals OTUD6B regulation of stress granule dynamics through coalescence with VCP/p97.
Yang D et al.·Cell Death Dis
2026Open Access
RETRACTION: lncRNA OTUD6B-AS1 Exacerbates As2O3-Induced Oxidative Damage in Bladder Cancer via miR-6734-5p-Mediated Functional Inhibition of IDH2.
Cellular Longevity OMA.·Oxid Med Cell Longev
2025Open AccessFunctional
Novel variant causing OTUD6B-related syndrome with ocular dysplasia and hypothyroidism: the first Chinese case.
Chen J et al.·BMC Pediatr
2025Open Access
ATRA upregulates OTUD6B to recruit CD8+ T cells to suppress colorectal liver metastasis by stabilizing DDX5/STAT3/CXCL11 axis.
Li J et al.·Cell Death Dis
2025Open Access
Dual role of lncRNA OTUD6B-AS1 in immune evasion and ferroptosis resistance: A prognostic and therapeutic biomarker in breast cancer.
Zhang JN et al.·Noncoding RNA Res
2025Open Access
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients