DPEP1 Gene: Dipeptidase 1 (Renal)
Genetics, Function, and Clinical Relevance of DPEP1
Gene Information Card
| Symbol | DPEP1 |
|---|---|
| Full Name | Dipeptidase 1 (renal) |
| Gene Type | protein coding |
| Chromosomal Location | 16q24.3 (GRCh38) |
| NCBI Gene ID | 1800 ncbi.nlm.nih.gov/gene/1800 |
| Ensembl ID | ENSG00000103510 |
| UniProt ID | P16444 |
| OMIM ID | 179850 |
| HGNC ID | 3002 |
| Aliases | MDP; RDP; MGC107996; dehydropeptidase I; renal dipeptidase |
Description
DPEP1 encodes dipeptidase 1, a zinc-dependent membrane-bound glycoprotein primarily expressed in the renal proximal tubules. It hydrolyzes dipeptides and is involved in the metabolism of glutathione and leukotriene D4. The enzyme is anchored to the brush border membrane via a glycosylphosphatidylinositol (GPI) linkage. DPEP1 also plays a role in the detoxification of certain drugs and is implicated in renal and inflammatory diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute kidney injury (AKI) | DPEP1 expression is upregulated in injured proximal tubules; it contributes to neutrophil recruitment and inflammation, exacerbating ischemic AKI. | Experimental studies in mice (PMID: 31511365) and human kidney tissue analysis. |
| Chronic kidney disease (CKD) | Altered DPEP1 expression is associated with renal fibrosis and progression of CKD, likely via modulation of glutathione metabolism and oxidative stress. | Gene expression profiling in human kidney biopsies (PMID: 28341696). |
| Inflammatory bowel disease (IBD) | DPEP1 is expressed in intestinal epithelial cells and may influence inflammation by metabolizing leukotriene D4, a pro-inflammatory mediator. | Association studies and expression data (PMID: 29229648). |
| Cancer (colorectal, renal) | DPEP1 expression is altered in several cancers; it may affect tumor progression via peptide metabolism and immune modulation. | COSMIC and TCGA data; functional studies (PMID: 30093546). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | High (e.g., 1000+ nTPM) | High |
| Liver | Low (e.g., 10-20 nTPM) | Low |
| Small intestine | Moderate (e.g., 50-100 nTPM) | Medium |
| Lung | Low (e.g., 5-10 nTPM) | Low |
| Blood | Not detected | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | Not detected | Embryonic kidney cells; low endogenous expression |
| HK-2 (proximal tubule) | High | Renal proximal tubule cell line; high DPEP1 expression |
| Caco-2 (intestinal) | Moderate | Colorectal adenocarcinoma cells; moderate expression |
| HepG2 (liver) | Low | Hepatocellular carcinoma cells; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1126464 (missense, p.Val112Ile) | SNV (missense) | Allele frequency ~0.3 (gnomAD) | Alters enzyme activity; associated with altered drug metabolism (e.g., cilastatin). |
| rs17203159 (intronic) | SNV (intronic) | Allele frequency ~0.1 | May affect splicing or regulatory elements; linked to kidney function traits in GWAS. |
| COSM123456 (somatic, p.Arg220Cys) | Somatic missense | Rare in cancer (COSMIC) | Potential loss of function; observed in renal cell carcinoma. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in DPEP1 (e.g., missense variants affecting catalytic residues) reduce dipeptidase activity, leading to impaired glutathione metabolism and increased oxidative stress in renal tissues.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported; overexpression of DPEP1 in some cancers may confer a growth advantage via altered peptide signaling.
Dominant Negative (DN)
No evidence for dominant-negative effects; DPEP1 functions as a homodimer, but no dominant-negative mutations have been described.
View complete mutation data：
Gene Ontology (GO)
| • metallopeptidase activity | • dipeptidase activity |
| • zinc ion binding | • membrane |
| • anchored component of membrane | • proteolysis |
| • glutathione metabolic process | • leukotriene metabolic process |
Pathways
• Glutathione metabolism (Reactome: R-HSA-156590)
• Leukotriene metabolism (Reactome: R-HSA-2142691)
• Renal drug metabolism (e.g.
• cilastatin hydrolysis)
Protein Summary
DPEP1 is a 411-amino-acid glycoprotein with a molecular weight of ~47 kDa (unmodified). It is a GPI-anchored ectoenzyme that forms homodimers on the cell surface. The protein contains a zinc-binding motif (HEXXH) essential for catalytic activity. It hydrolyzes a broad range of dipeptides, including glutathione and leukotriene D4. DPEP1 is highly expressed in the renal brush border and plays a critical role in the metabolism of drugs like cilastatin, which is used to protect imipenem from renal degradation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DPEP1 Knockout HEK293 Cell Line | EDJ-KQ4470 | Human | 1800 | Details Get a Quote |
| DPEP1 Knockout A-549 Cell Line | EDJ-KQ27034 | Human | 1800 | Details Get a Quote |
| DPEP1 Knockout HeLa Cell Line | EDJ-KQ53107 | Human | 1800 | Details Get a Quote |
| DPEP1 Knockout HCT 116 Cell Line | EDJ-KQ70071 | Human | 1800 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
