JOSD2
protein-codingJosephin domain containing 2, the group of MJD deubiquinating enzymes
Gene summary
This gene encodes a protein containing a Josephin domain. Josephin domain-containing proteins are deubiquitinating enzymes which catalyze the hydrolysis of the bond between the C-terminal glycine of the ubiquitin peptide and protein substrates. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jul 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.2 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 JOSD2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001270639.2. 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 | 1 | 1 | 2 | |||
| missense | 37 | 37 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 38 | 1 | 0 | 39 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001257568.1 | 4 | MANE Select | |
| Ensembl | ENSP00000468956.2 | 4 | MANE Select | |
| RefSeq | NP_001257569.1 | 4 | Standard | |
| RefSeq | NP_001257570.1 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| josd2 | 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
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000598418
- Coding exons
- 4
- Length
- 5356
- Individuals with no LoFs
- 125298
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125306
- p
- 0.0000319
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.834 | 95 | 121 | 0.786 | 0.00000810 | 1169 |
| Missense (PolyPhen) | 35 | 50.233 | 0.69675 | 512 | ||
| Synonymous | 0.416 | 57 | 61.1 | 0.932 | 0.00000422 | 436 |
| Loss of Function | 0.324 | 6 | 6.92 | 0.867 | 2.97e-7 | 71 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000018 | 0.000018 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Cleaves 'Lys-63'-linked poly-ubiquitin chains, and with lesser efficiency 'Lys-48'-linked poly-ubiquitin chains (in vitro). May act as a deubiquitinating enzyme. {ECO:0000269|PubMed:17696782, ECO:0000269|PubMed:21118805, ECO:0000269|PubMed:23625928}.;
Recessive Scores
- pRec
- 0.107
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.434
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |