USP42
protein-codingubiquitin specific peptidase 42, the group of Ubiquitin specific peptidases
Gene summary
Enables cysteine-type deubiquitinase activity. Predicted to be involved in protein deubiquitination; regulation of apoptotic process; and regulation of protein stability. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and 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 ~56.6 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 USP42 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_032172.3. 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 | 3 | 3 | 1 | 7 | ||
| missense | 315 | 26 | 341 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 321 | 29 | 1 | 351 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_115548.1 | 16 | MANE Select | |
| Ensembl | ENSP00000301962.5 | 16 | MANE Select | |
| RefSeq | NP_001352693.1 | 15 | Standard | |
| RefSeq | NP_001376579.1 | 16 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp42 | Danio rerio | Structure: trunk Quality: bent abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Post-translational protein modification
- Metabolism of proteins
- Ub-specific processing proteases
- Deubiquitination
Biological Process
- ubiquitin-dependent protein catabolic process
- spermatogenesis
- protein deubiquitination
- cell differentiation
- regulation of apoptotic process
Molecular Function
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306177
- Coding exons
- 16
- Length
- 56681
- Individuals with no LoFs
- 124547
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 108
- Defined
- 124655
- p
- 0.000433
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.63 | 916 | 787 | 1.16 | 0.0000508 | 8497 |
| Missense (PolyPhen) | 217 | 297.6 | 0.72916 | 3669 | ||
| Synonymous | -3.62 | 414 | 330 | 1.25 | 0.0000246 | 2550 |
| Loss of Function | 6.10 | 2 | 47.2 | 0.0423 | 0.00000233 | 619 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00020 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.0050 | 0.0049 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.000097 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00017 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinating enzyme which may play an important role during spermatogenesis. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.106
Intolerance Scores
- LoFtool
- 0.284
- RVIS EVS
- 0.52
- RVIS percentile EVS
- 80.4
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.503
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |