OTUD1

Chr 10

OTU deubiquitinase 1

Also known as: DUBA7, OTDC1

The OTUD1 protein is a deubiquitinating enzyme that specifically cleaves lysine-63-linked polyubiquitin chains and regulates ribosomal protein stability to ensure proper translation of mRNAs containing rare codons. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures, typically presenting in infancy. This gene shows moderate constraint against loss-of-function variants (LOEUF 0.619), suggesting some tolerance to haploinsufficiency.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
25
Pubs (1 yr)
9
P/LP submissions
0%
P/LP missense
0.62
LOEUF
LOF
Mechanism· predicted
Clinical SummaryOTUD1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.65) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
9 unique Pathogenic / Likely Pathogenic· 101 VUS of 128 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.62LOEUF
pLI 0.651
Z-score 2.23
OE 0.13 (0.040.62)
Moderately constrained

Typical tolerance to LoF variation

Missense Constraint
1.26Z-score
OE missense 0.71 (0.600.83)
104 obs / 147.1 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.13 (0.040.62)
00.351.4
Missense OE0.71 (0.600.83)
00.61.4
Synonymous OE0.98
01.21.6
LoF obs/exp: 1 / 7.7Missense obs/exp: 104 / 147.1Syn Z: 0.13
DN
0.3495th %ile
GOF
0.6346th %ile
LOF
0.64top 25%

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

LOFprediction above median

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

ClinVar Variant Classifications

128 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic1
VUS101
Likely Benign11
Benign6
8
Pathogenic
1
Likely Pathogenic
101
VUS
11
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
1
0
1
VUS
0
101
0
0
101
Likely Benign
0
4
0
7
11
Benign
0
2
1
3
6
Total01071010127

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

View in ClinVar →

Protein Context — Lollipop Plot

OTUD1 · 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.

Search ClinicalTrials.gov →
Clinical Literature
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