OTUD5

Chr XXLR

OTU deubiquitinase 5

Also known as: DUBA, MCAND

NCBI Gene: 55593ENSG00000068308UniProt: Q96G74

This gene encodes a member of the OTU (ovarian tumor) domain-containing cysteine protease superfamily. The OTU domain confers deubiquitinase activity and the encoded protein has been shown to suppress the type I interferon-dependent innate immune response by cleaving the polyubiquitin chain from an essential type I interferon adaptor protein. Cleavage results in disassociation of the adaptor protein from a downstream signaling complex and disruption of the type I interferon signaling cascade. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Oct 2008]

Primary Disease Associations & Inheritance

Multiple congenital anomalies-neurodevelopmental syndrome, X-linkedMIM #301056
XLR
0
Active trials
69
Pathogenic / LP
160
ClinVar variants
17
Pubs (1 yr)
4.0
Missense Z· constrained
0.17
LOEUF· LoF intolerant
Clinical Summary— OTUD5
🧬
Gene-Disease Validity (ClinGen)
multiple congenital anomalies-neurodevelopmental syndrome, X-linked · XLModerate

Moderate evidence — consider for supplementary testing

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
69 Pathogenic / Likely Pathogenic· 75 VUS of 160 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 0.997
Z-score 3.85
OE 0.00 (0.00–0.17)
Highly constrained

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

Missense Constraint
3.99Z-score
OE missense 0.21 (0.17–0.28)
44 obs / 204.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.00–0.17)
0≤0.351.4
Missense OE0.21 (0.17–0.28)
0≤0.61.4
Synonymous OE0.99
0≤1.21.6
LoF obs/exp: 0 / 17.2Missense obs/exp: 44 / 204.9Syn Z: 0.05
LOF
DN
0.18100th %ile
GOF
0.4184th %ile
LOF
0.85top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.17

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

160 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic64
Likely Pathogenic5
VUS75
Likely Benign11
Benign1
Conflicting4
64
Pathogenic
5
Likely Pathogenic
75
VUS
11
Likely Benign
1
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
4
60
0
64
Likely Pathogenic
1
3
1
0
5
VUS
1
63
11
0
75
Likely Benign
0
1
1
9
11
Benign
0
0
0
1
1
Conflicting
—4
Total2717310160

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

View in ClinVar →

OTUD5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

OTUD5-related neurodevelopmental disorder

strong
Monoallelic X HemizygousUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantinframe deletion

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
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