USP10
protein-codingubiquitin specific peptidase 10, the group of Ubiquitin specific peptidases
Gene summary
Ubiquitin is a highly conserved protein that is covalently linked to other proteins to regulate their function and degradation. This gene encodes a member of the ubiquitin-specific protease family of cysteine proteases. The enzyme specifically cleaves ubiquitin from ubiquitin-conjugated protein substrates. The protein is found in the nucleus and cytoplasm. It functions as a co-factor of the DNA-bound androgen receptor complex, and is inhibited by a protein in the Ras-GTPase pathway. The human genome contains several pseudogenes similar to this gene. Several transcript variants, some protein-coding and others not protein-coding, have been found for this gene. [provided by RefSeq, Jan 2013]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~79.9 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 USP10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005153.3. 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 | 2 | 1 | 3 | |||
| missense | 144 | 8 | 152 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 148 | 9 | 0 | 157 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005144.2 | 14 | MANE Select | |
| Ensembl | ENSP00000219473.7 | 14 | MANE Select | |
| RefSeq | NP_001259004.1 | 14 | Standard | |
| Ensembl | ENSP00000445589.2 | 3 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp10 | Danio rerio | Structure: post-vent region Quality: curled abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- DNA Repair
- Post-translational protein modification
- Metabolism of proteins
- Ub-specific processing proteases
- Deubiquitination
Biological Process
- ubiquitin-dependent protein catabolic process
- autophagy
- cellular response to DNA damage stimulus
- regulation of autophagy
- protein deubiquitination
Molecular Function
- p53 binding
- RNA binding
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- early endosome
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000219473
- Coding exons
- 14
- Length
- 79945
- Individuals with no LoFs
- 124298
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 345
- Defined
- 124643
- p
- 0.00138
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.674 | 494 | 454 | 1.09 | 0.0000256 | 5158 |
| Missense (PolyPhen) | 116 | 162.09 | 0.71565 | 1942 | ||
| Synonymous | -2.29 | 227 | 187 | 1.21 | 0.0000121 | 1611 |
| Loss of Function | 4.90 | 5 | 37.3 | 0.134 | 0.00000205 | 434 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00028 | 0.00026 | rare |
| Latino/Admixed American | 0.000094 | 0.000087 | rare |
| Ashkenazi Jewish | 0.0020 | 0.0019 | notable |
| East Asian | 0.017 | 0.017 | notable |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.000097 | rare |
| South Asian | 0.00025 | 0.00023 | rare |
| Other | 0.00035 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolase that can remove conjugated ubiquitin from target proteins such as p53/TP53, BECN1, SNX3 and CFTR. Acts as an essential regulator of p53/TP53 stability: in unstressed cells, specifically deubiquitinates p53/TP53 in the cytoplasm, leading to counteract MDM2 action and stabilize p53/TP53. Following DNA damage, translocates to the nucleus and deubiquitinates p53/TP53, leading to regulate the p53/TP53-dependent DNA damage response. Component of a regulatory loop that controls autophagy and p53/TP53 levels: mediates deubiquitination of BECN1, a key regulator of autophagy, leading to stabilize the PIK3C3/VPS34- containing complexes. In turn, PIK3C3/VPS34-containing complexes regulate USP10 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Does not deubiquitinate MDM2. Deubiquitinates CFTR in early endosomes, enhancing its endocytic recycling. Involved in a TANK-dependent negative feedback response to attenuate NF-kappaB activation via deubiquitinating IKBKG or TRAF6 in response to interleukin-1-beta (IL1B) stimulation or upon DNA damage (PubMed:25861989). Deubiquitinates TBX21 leading to its stabilization (PubMed:24845384). {ECO:0000269|PubMed:11439350, ECO:0000269|PubMed:18632802, ECO:0000269|PubMed:19398555, ECO:0000269|PubMed:20096447, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:24845384, ECO:0000269|PubMed:25861989}.;
Recessive Scores
- pRec
- 0.105
Intolerance Scores
- LoFtool
- 0.523
- RVIS EVS
- -0.24
- RVIS percentile EVS
- 36.31
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- S
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.501
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |