USP1
protein-codingubiquitin specific peptidase 1, the group of Ubiquitin specific peptidases
Gene summary
This gene encodes a member of the ubiquitin-specific processing (UBP) family of proteases that is a deubiquitinating enzyme (DUB) with His and Cys domains. This protein is located in the cytoplasm and cleaves the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins. The protein specifically deubiquitinates a protein in the Fanconi anemia (FA) DNA repair pathway. Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: Unknown
Disease ID:MONDO:0007661
Submitter: Labcorp Genetics (formerly Invitae)
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to USP1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003368.5. 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 | 2 | 2 | ||||
| missense | 81 | 3 | 84 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 83 | 3 | 2 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003359.3 | 8 | MANE Select | |
| Ensembl | ENSP00000343526.4 | 8 | MANE Select | |
| RefSeq | NP_001017415.1 | 8 | Standard | |
| RefSeq | NP_001017416.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| usp1 | Danio rerio | Structure: post-vent region Quality: curled abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Fanconi anemia pathway - Homo sapiens (human)
- miR-targeted genes in leukocytes - TarBase
- miR-targeted genes in lymphocytes - TarBase
- miR-targeted genes in muscle cell - TarBase
- miR-517 relationship with ARCN1 and USP1
Biological Process
- skeletal system development
- DNA repair
- regulation of DNA repair
- ubiquitin-dependent protein catabolic process
- response to UV
Molecular Function
- cysteine-type endopeptidase activity
- thiol-dependent ubiquitin-specific protease activity
- protein binding
- peptidase activity
- thiol-dependent ubiquitinyl hydrolase activity
Cellular Component
- nucleus
- nucleoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000339950
- Coding exons
- 8
- Length
- 15508
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125739
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.06 | 321 | 379 | 0.847 | 0.0000171 | 5204 |
| Missense (PolyPhen) | 64 | 143.54 | 0.44588 | 2023 | ||
| Synonymous | -0.738 | 148 | 137 | 1.08 | 0.00000668 | 1419 |
| Loss of Function | 4.59 | 3 | 30.2 | 0.0993 | 0.00000144 | 456 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000063 | 0.000062 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Negative regulator of DNA damage repair which specifically deubiquitinates monoubiquitinated FANCD2 (PubMed:15694335). Also involved in PCNA-mediated translesion synthesis (TLS) by deubiquitinating monoubiquitinated PCNA (PubMed:16531995). Has almost no deubiquitinating activity by itself and requires the interaction with WDR48 to have a high activity (PubMed:18082604, PubMed:26388029). {ECO:0000269|PubMed:15694335, ECO:0000269|PubMed:16531995, ECO:0000269|PubMed:18082604, ECO:0000269|PubMed:26388029}.;
Recessive Scores
- pRec
- 0.138
Intolerance Scores
- LoFtool
- 0.535
- RVIS EVS
- -0.64
- RVIS percentile EVS
- 16.63
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.898
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |