PRSS1 (Serine Protease 1) Gene
Key genetic factor in hereditary pancreatitis and pancreatic cancer susceptibility
Gene Information Card
| Symbol | PRSS1 |
|---|---|
| Full Name | Serine Protease 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q34 |
| NCBI Gene ID | 5644 ncbi.nlm.nih.gov/gene/5644 |
| Ensembl ID | ENSG00000204983 |
| UniProt ID | P07477 |
| OMIM ID | 276000 |
| HGNC ID | 9475 |
| Aliases | TRY1, TRY4, TRYP1, TRYPSIN1, cationic trypsinogen |
Description
PRSS1 encodes the cationic trypsinogen, a serine protease precursor predominantly expressed in the pancreas. Trypsinogen is activated to trypsin, a key digestive enzyme that cleaves peptide bonds. Mutations in PRSS1 are the most common cause of hereditary pancreatitis and increase the risk of pancreatic ductal adenocarcinoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary pancreatitis | Gain-of-function mutations (e.g., R122H, N29I) enhance autoactivation or impair trypsin degradation, leading to premature trypsin activation within the pancreas and autodigestion. | OMIM #167800; ClinVar; multiple case-control studies |
| Pancreatic cancer | Chronic inflammation from recurrent pancreatitis promotes acinar-to-ductal metaplasia and oncogenic KRAS mutations. PRSS1 mutation carriers have a 40-55% lifetime risk of pancreatic cancer. | OMIM #260350; COSMIC; large cohort studies |
| Pancreatitis (sporadic) | Rare PRSS1 variants (e.g., A16V, K23R) with incomplete penetrance contribute to sporadic acute or chronic pancreatitis. | ClinVar; NCBI dbSNP |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Pancreas | 12567.2 | High |
| Salivary gland | 2.1 | Low |
| Stomach | 0.8 | Not detected |
| Duodenum | 0.5 | Not detected |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PANC-1 (pancreatic carcinoma) | 1450 | Moderate expression |
| MIA PaCa-2 (pancreatic carcinoma) | 820 | Low expression |
| BxPC-3 (pancreatic adenocarcinoma) | 2100 | Moderate expression |
| HPDE (normal pancreatic ductal) | 9800 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R122H | Missense (c.365G>A) | ~70% of hereditary pancreatitis families | Gain-of-function: prevents trypsin autolysis, prolonging trypsin activity |
| N29I | Missense (c.86A>T) | ~20% of hereditary pancreatitis families | Gain-of-function: enhances autoactivation of trypsinogen |
| A16V | Missense (c.47C>T) | <5% of hereditary pancreatitis families | Gain-of-function: increased trypsinogen activation |
| K23R | Missense (c.68A>G) | Rare | Gain-of-function: altered activation peptide cleavage |
| D22G | Missense (c.65A>G) | Rare | Gain-of-function: increased autoactivation |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations; PRSS1 is essential for digestion and complete loss is likely incompatible with normal pancreatic function.
Gain of Function (GOF)
Most pathogenic mutations (R122H, N29I, A16V, K23R, D22G) are gain-of-function, leading to increased trypsin activity or resistance to degradation, causing premature trypsin activation and pancreatitis.
Dominant Negative (DN)
Not described for PRSS1; all known pathogenic mutations act via gain-of-function or increased autoactivation.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG: hsa04972 – Pancreatic secretion
• KEGG: hsa04610 – Complement and coagulation cascades (trypsin involvement)
• Reactome: R-HSA-6811434 – Trypsin activates PARs
• Reactome: R-HSA-166658 – Trypsin-mediated activation of trypsinogen
Protein Summary
Cationic trypsinogen (PRSS1) is a 247-amino-acid zymogen synthesized in pancreatic acinar cells. Upon secretion into the duodenum, enteropeptidase cleaves the activation peptide to yield active trypsin. Trypsin then activates other pancreatic zymogens. The protein contains a catalytic triad (His57, Asp102, Ser195) typical of serine proteases. Mutations that stabilize the active form or prevent autolysis cause hereditary pancreatitis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PRSS1 Knockout HEK293 Cell Line | EDJ-KQ4797 | Human | 5644 | Details Get a Quote |
| PRSS12 Knockout HEK293 Cell Line | EDJ-KQ6254 | Human | 8492 | Details Get a Quote |
| PRSS16 Knockout HEK293 Cell Line | EDJ-KQ6993 | Human | 10279 | Details Get a Quote |
| PRSS12 Knockout HCT 116 Cell Line | EDJ-KQ30128 | Human | 8492 | Details Get a Quote |
| PRSS12 Knockout HeLa Cell Line | EDJ-KQ30129 | Human | 8492 | Details Get a Quote |
| PRSS16 Knockout HCT 116 Cell Line | EDJ-KQ30334 | Human | 10279 | Details Get a Quote |
| PRSS16 Knockout A-549 Cell Line | EDJ-KQ31714 | Human | 10279 | Details Get a Quote |
| PRSS16 Knockout HeLa Cell Line | EDJ-KQ31716 | Human | 10279 | Details Get a Quote |
| PRSS1 Knockout HeLa Cell Line | EDJ-KQ54227 | Human | 5644 | Details Get a Quote |
| PRSS1 Knockout A-549 Cell Line | EDJ-KQ62720 | Human | 5644 | Details Get a Quote |
| PRSS12 Knockout A-549 Cell Line | EDJ-KQ63406 | Human | 8492 | Details Get a Quote |
| PRSS1 Knockout HCT 116 Cell Line | EDJ-KQ71192 | Human | 5644 | Details Get a Quote |
