OTUD5

Chr XXLR

OTU deubiquitinase 5

Also known as: DUBA, MCAND

The protein functions as a deubiquitinase that suppresses type I interferon-dependent innate immune responses by cleaving polyubiquitin chains from essential interferon adaptor proteins, disrupting downstream signaling cascades. Loss-of-function mutations cause X-linked recessive multiple congenital anomalies-neurodevelopmental syndrome. The mechanism involves haploinsufficiency leading to dysregulated innate immune signaling and abnormal neurodevelopment.

OMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismXLRLOEUF 0.171 OMIM phenotype
Clinical SummaryOTUD5
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Dual constrained — LoF & missense intolerant
LoF Constraint
0.17LOEUF
pLI 0.997
Z-score 3.85
OE 0.00 (0.000.17)
Highly constrained

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

Missense Constraint
3.99Z-score
OE missense 0.21 (0.170.28)
44 obs / 204.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios
LoF OE0.00 (0.000.17)
00.351.4
Missense OE0.21 (0.170.28)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 0 / 17.2Missense obs/exp: 44 / 204.9Syn Z: 0.05
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
strongOTUD5-related neurodevelopmental disorderOTHERXLR
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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

OTUD5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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