USP40 (Ubiquitin Specific Peptidase 40) Gene
Explore the USP40 gene: its location, function, expression, and associated diseases. Learn about its role in ubiquitin-dependent proteolysis and potential implications in cancer and other conditions.
Gene Information Card
| Symbol | USP40 |
|---|---|
| Full Name | Ubiquitin specific peptidase 40 |
| Gene Type | protein coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 55284 ncbi.nlm.nih.gov/gene/55284 |
| Ensembl ID | ENSG00000115155 |
| UniProt ID | Q9NVE5 |
| OMIM ID | 618465 |
| HGNC ID | 20082 |
| Aliases | FLJ12529, MGC126851 |
Description
USP40 (ubiquitin specific peptidase 40) is a protein-coding gene located on chromosome 2q37.3. It encodes a deubiquitinating enzyme that belongs to the ubiquitin-specific protease (USP) family. USP40 is involved in the removal of ubiquitin from target proteins, thereby regulating protein stability, cellular signaling, and various physiological processes. Its expression is widespread, with notable levels in the kidney, liver, and testis. USP40 has been implicated in several diseases, including cancer and neurodegenerative disorders, though its precise roles are still under investigation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | Altered expression and potential regulation of oncogenic pathways; deubiquitinase activity may stabilize oncoproteins or degrade tumor suppressors. | COSMIC: somatic mutations and copy number alterations observed in multiple cancer types; expression changes reported in literature. |
| Neurodegenerative disorders (e.g., Parkinson's disease) | Potential involvement in protein aggregation and clearance via ubiquitin-proteasome system; genetic variants may affect enzyme activity. | ClinVar: rare variants reported; limited functional studies suggest a role in neuronal protein homeostasis. |
| Kidney disease | High expression in kidney; possible role in renal cell function and injury response. | Expression data from GTEx and literature; no direct disease association confirmed yet. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 25.3 | High |
| Liver | 18.7 | Medium |
| Testis | 16.2 | Medium |
| Brain | 12.5 | Medium |
| Heart | 8.4 | Low |
| Lung | 7.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 20.1 | High expression in embryonic kidney cells |
| HepG2 | 15.4 | Liver cancer cell line with moderate expression |
| A549 | 10.2 | Lung carcinoma cell line with low expression |
| MCF7 | 8.7 | Breast cancer cell line with low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Ile412Val) | Missense | 0.5% (gnomAD) | Unknown; predicted benign by in silico tools |
| c.567C>T (p.Pro189Leu) | Missense | 0.1% (COSMIC) | Potential impact on protein stability; observed in colorectal cancer |
| c.2345_2346del (p.Leu782fs) | Frameshift | Rare | Loss of function; likely pathogenic if homozygous |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the protein are likely to result in loss of deubiquitinase activity, leading to accumulation of ubiquitinated substrates and disrupted cellular signaling.
Gain of Function (GOF)
Missense mutations that increase enzyme activity or alter substrate specificity could lead to excessive deubiquitination, potentially stabilizing oncoproteins or destabilizing tumor suppressors.
Dominant Negative (DN)
Some missense mutations may produce a protein that retains binding to substrates but lacks catalytic activity, thereby interfering with wild-type USP40 function in a dominant-negative manner.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase activity | • ubiquitin-specific protease activity |
| • proteolysis | • ubiquitin-dependent protein catabolic process |
| • protein deubiquitination |
Pathways
• Ubiquitin-Proteasome Dependent Proteolysis
• Protein modification and ubiquitination
Protein Summary
The USP40 protein is a deubiquitinating enzyme that cleaves ubiquitin moieties from target proteins, thereby regulating their stability and function. It contains a catalytic domain characteristic of ubiquitin-specific proteases. USP40 is widely expressed, with highest levels in kidney, liver, and testis. It plays a role in various cellular processes, including cell cycle control, DNA damage response, and signal transduction. Dysregulation of USP40 has been linked to cancer and other diseases, making it a potential therapeutic target.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| USP40 Knockout HEK293 Cell Line | EDJ-KQ16080 | Human | 55230 | Details Get a Quote |
| USP40 Knockout A-549 Cell Line | EDJ-KQ45990 | Human | 55230 | Details Get a Quote |
| USP40 Knockout HCT 116 Cell Line | EDJ-KQ47214 | Human | 55230 | Details Get a Quote |
| USP40 Knockout HeLa Cell Line | EDJ-KQ47215 | Human | 55230 | Details Get a Quote |
