JOSD1
protein-codingJosephin domain containing 1, the group of MJD deubiquinating enzymes
Gene summary
Predicted to enable cysteine-type deubiquitinase activity. Predicted to be involved in proteolysis. Predicted to act upstream of or within several processes, including endocytosis; membrane biogenesis; and protein deubiquitination. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~16.0 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 JOSD1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001360236.2. 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 | 15 | 15 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 16 | 0 | 0 | 16 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001347165.1 | 4 | MANE Select | |
| Ensembl | ENSP00000506752.1 | 4 | MANE Select | |
| RefSeq | NP_001347164.1 | 4 | Standard | |
| RefSeq | NP_055691.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| josd1 | Danio rerio | Structure: pharyngeal arch cartilage Quality: malformed abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Josephin domain DUBs
- Post-translational protein modification
- Metabolism of proteins
- Deubiquitination
Biological Process
- protein deubiquitination
Molecular Function
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- cytosol
- plasma membrane
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000216039
- Coding exons
- 4
- Length
- 16014
- Individuals with no LoFs
- 125743
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 5
- Defined
- 125748
- p
- 0.0000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 63 | 119 | 0.531 | 0.00000629 | 1335 |
| Missense (PolyPhen) | 13 | 38.768 | 0.33533 | 506 | ||
| Synonymous | -1.75 | 62 | 46.8 | 1.32 | 0.00000289 | 375 |
| Loss of Function | 1.97 | 4 | 11.1 | 0.362 | 6.21e-7 | 109 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinates monoubiquitinated probes (in vitro). When ubiquitinated, cleaves 'Lys-63'-linked and 'Lys-48'-linked poly-ubiquitin chains (in vitro), hence may act as a deubiquitinating enzyme. May increase macropinocytosis and suppress clathrin- and caveolae-mediated endocytosis. May enhance membrane dynamics and cell motility independently of its catalytic activity. {ECO:0000269|PubMed:21118805, ECO:0000269|PubMed:23625928}.;
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- LoFtool
- 0.245
- RVIS EVS
- -0.01
- RVIS percentile EVS
- 53.19
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.706
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |