USP13
protein-codingubiquitin specific peptidase 13, the group of Ubiquitin specific peptidases
Gene summary
Enables several functions, including BAT3 complex binding activity; peptidase activity; and proteasome binding activity. Involved in several processes, including maintenance of unfolded protein; positive regulation of ERAD pathway; and regulation of autophagy. Acts upstream of or within protein deubiquitination and protein stabilization. Predicted to be located in nucleoplasm. Predicted to be active in cytosol and nucleus. [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 ~151.3 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 USP13 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003940.3. 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 | 2 | 8 | ||
| missense | 127 | 127 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 11 | 11 | ||||
| Total | 0 | 0 | 141 | 3 | 2 | 146 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003931.2 | 21 | MANE Select | |
| Ensembl | ENSP00000263966.3 | 21 | MANE Select | |
| Ensembl | ENSP00000417146.1 | 20 | Standard | |
| Ensembl | ENSP00000420057.1 | 9 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp13 | 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
- Ub-specific processing proteases
Biological Process
- regulation of transcription, DNA-templated
- ubiquitin-dependent protein catabolic process
- autophagy
- cell population proliferation
- regulation of autophagy
Molecular Function
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- zinc ion binding
- ubiquitin protein ligase binding
Cellular Component
- nucleoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000263966
- Coding exons
- 21
- Length
- 136647
- Individuals with no LoFs
- 125665
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 83
- Defined
- 125748
- p
- 0.000330
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 376 | 495 | 0.760 | 0.0000266 | 5709 |
| Missense (PolyPhen) | 110 | 153.24 | 0.71781 | 1807 | ||
| Synonymous | 0.751 | 173 | 186 | 0.930 | 0.0000110 | 1600 |
| Loss of Function | 2.99 | 27 | 49.7 | 0.543 | 0.00000282 | 553 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.00052 | 0.00052 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0.00037 | 0.00037 | rare |
| European (Non-Finnish) | 0.00036 | 0.00036 | rare |
| South Asian | 0.00026 | 0.00026 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Deubiquitinase that mediates deubiquitination of target proteins such as BECN1, MITF, SKP2 and USP10 and is involved in various processes such as autophagy and endoplasmic reticulum- associated degradation (ERAD). 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. Also deubiquitinates USP10, an essential regulator of p53/TP53 stability. In turn, PIK3C3/VPS34- containing complexes regulate USP13 stability, suggesting the existence of a regulatory system by which PIK3C3/VPS34-containing complexes regulate p53/TP53 protein levels via USP10 and USP13. Recruited by nuclear UFD1 and mediates deubiquitination of SKP2, thereby regulating endoplasmic reticulum-associated degradation (ERAD). Also regulates ERAD through the deubiquitination of UBL4A a component of the BAG6/BAT3 complex. Mediates stabilization of SIAH2 independently of deubiquitinase activity: binds ubiquitinated SIAH2 and acts by impairing SIAH2 autoubiquitination. Has a weak deubiquitinase activity in vitro and preferentially cleaves 'Lys-63'-linked polyubiquitin chains. In contrast to USP5, it is not able to mediate unanchored polyubiquitin disassembly. Able to cleave ISG15 in vitro; however, additional experiments are required to confirm such data. {ECO:0000269|PubMed:17653289, ECO:0000269|PubMed:21571647, ECO:0000269|PubMed:21659512, ECO:0000269|PubMed:21811243, ECO:0000269|PubMed:21962518, ECO:0000269|PubMed:22216260, ECO:0000269|PubMed:24424410}.;
Recessive Scores
- pRec
- 0.132
Intolerance Scores
- LoFtool
- 0.769
- RVIS EVS
- -1.02
- RVIS percentile EVS
- 8.04
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.894
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |