USP7 (Ubiquitin Specific Peptidase 7)
A deubiquitinating enzyme regulating p53, MDM2, and other key cellular pathways; implicated in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | USP7 |
|---|---|
| Full Name | Ubiquitin Specific Peptidase 7 |
| Gene Type | Protein coding |
| Chromosomal Location | 16p13.2 |
| NCBI Gene ID | 7874 ncbi.nlm.nih.gov/gene/7874 |
| Ensembl ID | ENSG00000138685 |
| UniProt ID | Q93009 |
| OMIM ID | 602519 |
| HGNC ID | 12630 |
| Aliases | HAUSP, TEF1, CGI-11 |
Description
USP7 (Ubiquitin Specific Peptidase 7), also known as HAUSP (Herpesvirus-Associated Ubiquitin-Specific Protease), is a deubiquitinating enzyme that removes ubiquitin from target proteins, thereby regulating their stability and function. It plays a critical role in the p53/MDM2 pathway, DNA damage response, epigenetic regulation, and immune signaling. Mutations in USP7 are associated with neurodevelopmental disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia, behavioral abnormalities, and seizures (NEDHBS) | Loss-of-function mutations in USP7 impair deubiquitination of substrates such as p53 and MDM2, disrupting neuronal development and synaptic function. | ClinVar, OMIM #616901 |
| Prostate cancer | USP7 overexpression stabilizes MDM2, promoting p53 degradation and tumor progression. | COSMIC, PMID: 26921392 |
| Multiple myeloma | USP7 deubiquitinates and stabilizes the oncoprotein MYC, enhancing proliferation. | COSMIC, PMID: 27565344 |
| Colorectal cancer | USP7 overexpression correlates with poor prognosis; regulates β-catenin and p53 pathways. | COSMIC, PMID: 25329317 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 18.5 | Medium |
| Testis | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 10.1 | Low |
| Heart | 8.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 (embryonic kidney) | 22.4 | High expression |
| HeLa (cervical carcinoma) | 19.7 | High expression |
| K562 (leukemia) | 14.1 | Medium expression |
| HepG2 (hepatocellular carcinoma) | 11.3 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.208C>T (p.Arg70*) | Nonsense | <0.01% | Loss of function; associated with NEDHBS |
| c.512G>A (p.Arg171Gln) | Missense | <0.01% | Loss of function; reduced deubiquitinase activity |
| c.2155C>T (p.Arg719Trp) | Missense | <0.01% | Loss of function; impaired substrate binding |
| c.2633A>G (p.Tyr878Cys) | Missense | <0.01% | Loss of function; altered protein stability |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations in USP7 are loss-of-function, leading to reduced deubiquitinase activity and dysregulation of substrates like p53, MDM2, and FOXO4. These are primarily associated with neurodevelopmental disorders.
Gain of Function (GOF)
Gain-of-function mutations are rare but may involve overexpression or increased catalytic activity, observed in some cancers where USP7 stabilizes oncoproteins.
Dominant Negative (DN)
Dominant-negative effects have been proposed for certain missense mutations that retain partial activity but disrupt normal USP7 complex formation, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type deubiquitinase activity | • protein deubiquitination |
| • ubiquitin-dependent protein catabolic process | • regulation of protein stability |
| • DNA damage response | • chromatin remodeling |
| • negative regulation of apoptotic process | • viral process |
Pathways
• p53 pathway (Reactome: R-HSA-3700989)
• MDM2-mediated degradation of p53 (Reactome: R-HSA-6804756)
• Deubiquitination (Reactome: R-HSA-5688426)
• Regulation of FOXO transcription factors (Reactome: R-HSA-9614085)
Protein Summary
USP7 is a 1102-amino acid deubiquitinating enzyme containing a TRAF-like domain, a catalytic USP domain, and multiple ubiquitin-like domains. It removes ubiquitin from specific substrates, including p53, MDM2, FOXO4, and PTEN, thereby regulating their stability and cellular localization. USP7 is essential for embryonic development, DNA repair, and immune responses. Its dysregulation contributes to cancer and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP7 Knockout HAP1 Cell Line | EDC08040 | Human | 7874 | Details Get a Quote |
