USPL1
protein-codingubiquitin specific peptidase like 1, the group of Ubiquitin specific peptidase like |Ubiquitin specific peptidases
Gene summary
Enables SUMO binding activity and deSUMOylase activity. Involved in several processes, including Cajal body organization; protein desumoylation; and snRNA transcription. Located in Cajal body. [provided by Alliance of Genome Resources, Jul 2025]
- C13orf22
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~43.1 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 USPL1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005800.5. 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 | 156 | 19 | 175 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 158 | 19 | 0 | 177 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005791.3 | 8 | MANE Select | |
| Ensembl | ENSP00000255304.4 | 8 | MANE Select | |
| RefSeq | NP_001308461.1 | 6 | Standard | |
| RefSeq | NP_001308462.1 | 4 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| uspl1 | Danio rerio | Structure: trunk Quality: curved dorsal abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- cell population proliferation
- snRNA transcription
- protein desumoylation
- Cajal body organization
Molecular Function
- protein binding
- SUMO binding
- ubiquitin binding
- SUMO-specific isopeptidase activity
Cellular Component
- extracellular space
- Cajal body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000255304
- Coding exons
- 8
- Length
- 41857
- Individuals with no LoFs
- 125714
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125748
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.427 | 528 | 556 | 0.949 | 0.0000269 | 7142 |
| Missense (PolyPhen) | 115 | 139.76 | 0.82284 | 1985 | ||
| Synonymous | 0.0532 | 209 | 210 | 0.995 | 0.0000108 | 2121 |
| Loss of Function | 4.24 | 11 | 39.9 | 0.276 | 0.00000191 | 570 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.00017 | 0.00017 | rare |
| South Asian | 0.00023 | 0.00023 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: SUMO-specific isopeptidase involved in protein desumoylation. Specifically binds SUMO proteins with a higher affinity for SUMO2 and SUMO3 which it cleaves more efficiently. Also able to process full-length SUMO proteins to their mature forms (PubMed:22878415). Plays a key role in RNA polymerase-II- mediated snRNA transcription in the Cajal bodies (PubMed:24413172). Is a component of complexes that can bind to U snRNA genes (PubMed:24413172). {ECO:0000269|PubMed:22878415, ECO:0000269|PubMed:24413172}.;
Recessive Scores
- pRec
- 0.0852
Intolerance Scores
- LoFtool
- 0.724
- RVIS EVS
- 0.45
- RVIS percentile EVS
- 78.05
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.948
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | High |
| Cancer | Medium | Medium | Medium |