PREP (Prolyl Endopeptidase) Gene: Function, Expression, and Clinical Significance
Comprehensive resource on the PREP gene, including genomic context, protein function, tissue expression, associated diseases, and mutation landscape.
Gene Information Card
| Symbol | PREP |
|---|---|
| Full Name | prolyl endopeptidase |
| Gene Type | protein coding |
| Chromosomal Location | 6q22.31 |
| NCBI Gene ID | 5550 ncbi.nlm.nih.gov/gene/5550 |
| Ensembl ID | ENSG00000103657 |
| UniProt ID | P48147 |
| OMIM ID | 600400 |
| HGNC ID | 9358 |
| Aliases | PE, PEPT, prolyl oligopeptidase |
Description
The PREP gene encodes prolyl endopeptidase (also known as prolyl oligopeptidase), a serine protease that cleaves peptide bonds at the C-terminal side of proline residues. This enzyme is involved in the maturation and degradation of peptide hormones and neuropeptides, and has been implicated in various physiological processes including learning, memory, and blood pressure regulation. PREP is widely expressed in multiple tissues, with highest levels in the brain, and has been studied in the context of neuropsychiatric disorders, cancer, and hypertension.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypertension | PREP degrades bradykinin and other vasoactive peptides, influencing blood pressure regulation. | PMID: 10486221; OMIM 600400 |
| Alzheimer's disease | PREP activity is altered in brain regions affected by Alzheimer's, potentially affecting amyloid precursor protein processing. | PMID: 10486221; OMIM 600400 |
| Major depressive disorder | Genetic variants in PREP have been associated with depression in some populations. | PMID: 10486221; OMIM 600400 |
| Cancer (various) | PREP expression is dysregulated in several cancers, affecting tumor progression and metastasis. | COSMIC; PMID: 10486221 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | High | High |
| Lung | Medium | Medium |
| Kidney | Medium | Medium |
| Liver | Low | Low |
| Heart | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | Medium | Cervical cancer cell line |
| A549 | Medium | Lung carcinoma cell line |
| HepG2 | Low | Hepatocellular carcinoma cell line |
| SH-SY5Y | High | Neuroblastoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1042C>T (p.Arg348Cys) | Missense | Rare | Reported in ClinVar; functional impact not fully characterized |
| c.1573G>A (p.Val525Ile) | Missense | Rare | Reported in ClinVar; likely benign |
| c.1648C>T (p.Arg550Cys) | Missense | Rare | Reported in ClinVar; uncertain significance |
| c.1966G>A (p.Val656Met) | Missense | Rare | Reported in ClinVar; uncertain significance |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in PREP are rare and not well-documented; complete loss may be lethal or compensated by other proteases.
Gain of Function (GOF)
Gain-of-function mutations have not been reported; increased PREP activity may be due to overexpression rather than mutation.
Dominant Negative (DN)
No dominant-negative mutations have been described for PREP.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity | • prolyl oligopeptidase activity |
| • proteolysis | • peptide metabolic process |
| • cytoplasm | • cytosol |
| • extracellular exosome |
Pathways
• Prolyl oligopeptidase pathway
• Neuropeptide processing
• Renin-angiotensin system (via bradykinin degradation)
Protein Summary
Prolyl endopeptidase (PREP) is a 76 kDa cytosolic serine protease that specifically hydrolyzes proline-containing peptides. It is composed of a peptidase S9 domain and a seven-bladed beta-propeller domain that restricts access to the active site. PREP is involved in the maturation and degradation of neuropeptides such as substance P, thyrotropin-releasing hormone, and bradykinin. It is highly expressed in the brain and has been implicated in cognitive function, mood regulation, and blood pressure control. PREP also interacts with proteins involved in cytoskeletal dynamics and cell signaling, suggesting additional non-proteolytic functions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PREP Knockout HEK293 Cell Line | EDJ-KQ5530 | Human | 5550 | Details Get a Quote |
| PREPL Knockout HEK293 Cell Line | EDJ-KQ6645 | Human | 9581 | Details Get a Quote |
| PREPL Knockout A-549 Cell Line | EDJ-KQ30921 | Human | 9581 | Details Get a Quote |
| PREPL Knockout HCT 116 Cell Line | EDJ-KQ30922 | Human | 9581 | Details Get a Quote |
| PREP Knockout A-549 Cell Line | EDJ-KQ28775 | Human | 5550 | Details Get a Quote |
| PREP Knockout HCT 116 Cell Line | EDJ-KQ28776 | Human | 5550 | Details Get a Quote |
| PREP Knockout HeLa Cell Line | EDJ-KQ28777 | Human | 5550 | Details Get a Quote |
| PREPL Knockout HeLa Cell Line | EDJ-KQ29570 | Human | 9581 | Details Get a Quote |
