OTUD3
protein-codingOTU deubiquitinase 3, the group of OTU domain containing
Gene summary
Enables cysteine-type deubiquitinase activity. Involved in cellular response to nutrient levels and protein deubiquitination. Acts upstream of or within negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; protein deubiquitination; and protein stabilization. Located in cytoplasm. Is active in nucleus. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.6 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to OTUD3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015207.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 0 | |||||
| missense | 45 | 2 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 48 | 2 | 0 | 50 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056022.1 | 8 | MANE Select | |
| Ensembl | ENSP00000364261.3 | 8 | MANE Select | |
| Ensembl | ENSP00000550312.1 | 6 | Standard | |
| Ensembl | ENSP00000550312.1 | 6 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| otud3 | Danio rerio | Structure: post-vent region Quality: curled abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signal Transduction
- Regulation of PTEN stability and activity
- Post-translational protein modification
- Metabolism of proteins
- PTEN Regulation
Biological Process
- protein deubiquitination
- protein K11-linked deubiquitination
- protein K6-linked deubiquitination
- protein stabilization
- negative regulation of protein kinase B signaling
Molecular Function
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375120
- Coding exons
- 8
- Length
- 30433
- Individuals with no LoFs
- 124730
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 76
- Defined
- 124806
- p
- 0.000305
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.766 | 169 | 199 | 0.847 | 0.0000110 | 2627 |
| Missense (PolyPhen) | 39 | 56.302 | 0.6927 | 750 | ||
| Synonymous | 1.10 | 61 | 73.0 | 0.836 | 0.00000418 | 723 |
| Loss of Function | 1.81 | 10 | 18.4 | 0.544 | 0.00000103 | 226 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.0012 | 0.0012 | notable |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00023 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinating enzyme that hydrolyzes 'Lys-6'- and 'Lys-11'-linked polyubiquitin. Also hydrolyzes heterotypic (mixed and branched) and homotypic chains. {ECO:0000269|PubMed:23827681}.;
Recessive Scores
- pRec
- 0.103
Intolerance Scores
- LoFtool
- 0.789
- RVIS EVS
- 0.35
- RVIS percentile EVS
- 74.18
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.543
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |