PRSS2: Serine Protease 2 (Trypsinogen-2) – Gene Information and Clinical Significance

Comprehensive overview of PRSS2, a key pancreatic trypsinogen gene implicated in pancreatitis and cancer.

Gene Information Card

Symbol PRSS2
Full Name Serine Protease 2
Gene Type protein-coding
Chromosomal Location 7q34
NCBI Gene ID 5645 ncbi.nlm.nih.gov/gene/5645
Ensembl ID ENSG00000125870
UniProt ID P07478
OMIM ID 601564
HGNC ID 9483
Aliases TRY2, TRY8, TRYP2, trypsinogen-2

Description

PRSS2 encodes trypsinogen-2, a serine protease precursor synthesized in the pancreas. It is secreted into the duodenum, where it is activated to trypsin-2, a key digestive enzyme that cleaves peptide bonds at lysine and arginine residues. PRSS2 is part of the trypsinogen family and plays a critical role in protein digestion. Mutations in PRSS2 have been associated with chronic pancreatitis and altered risk for pancreatic cancer.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Chronic Pancreatitis Loss-of-function variants (e.g., p.Gly191Arg) reduce trypsin activity, protecting against premature trypsin activation and pancreatitis. Gain-of-function variants (e.g., p.Asp22Ala) increase autoactivation risk. ClinVar, OMIM
Pancreatic Cancer Somatic mutations and altered expression of PRSS2 may contribute to tumor progression. COSMIC reports missense mutations in pancreatic adenocarcinoma. COSMIC, NCBI
Hereditary Pancreatitis Rare PRSS2 variants (e.g., p.Arg122His) have been linked to familial forms of pancreatitis. OMIM, ClinVar

Expression Profile

Tissue Expression
Tissue nTPM level
Pancreas 1234.5 High
Salivary Gland 12.3 Low
Stomach 8.7 Low
Duodenum 5.4 Low
Liver 1.2 Not detected
Cell Line Expression
Cell Line nTPM Notes
PANC-1 456.7 Pancreatic cancer cell line
MIA PaCa-2 389.2 Pancreatic cancer cell line
BxPC-3 512.3 Pancreatic cancer cell line
HeLa 2.1 Cervical cancer cell line (low expression)
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
p.Gly191Arg (c.571G>A) Missense 0.5% in general population Loss-of-function; protective against chronic pancreatitis
p.Asp22Ala (c.65A>C) Missense <0.1% Gain-of-function; increased trypsin autoactivation, risk factor for pancreatitis
p.Arg122His (c.365G>A) Missense <0.1% Associated with hereditary pancreatitis
c.−28A>G Promoter variant 1-2% May alter expression levels; uncertain significance
Mutation functional classification

Loss of Function (LOF)

p.Gly191Arg reduces catalytic activity, decreasing trypsinogen activation and protecting against pancreatitis.

Gain of Function (GOF)

p.Asp22Ala enhances autoactivation, predisposing to premature trypsin activation and pancreatitis.

Dominant Negative (DN)

No well-characterized dominant-negative mutations reported for PRSS2.

Pathways

• Digestion and absorption (Reactome: R-HSA-8963748)
• Trypsin activation cascade (Reactome: R-HSA-8963749)
• Pancreatic secretion (KEGG: hsa04972)

Protein Summary

PRSS2 encodes trypsinogen-2 (cationic trypsinogen), a 247-amino-acid zymogen. After secretion into the duodenum, it is cleaved by enteropeptidase to active trypsin-2. The protein contains a signal peptide (residues 1-15), an activation peptide (16-23), and a catalytic triad (His63, Asp108, Ser203). Trypsin-2 is a serine protease with broad substrate specificity, involved in digestion and extracellular matrix remodeling. Mutations affecting its activation or activity are linked to pancreatic disorders.

Related Products

Product name Cat.No. Species Gene ID
PRSS23 Knockout HEK293 Cell Line EDJ-KQ2267 Human 11098 Details Get a Quote
PRSS2 Knockout HEK293 Cell Line EDJ-KQ5553 Human 5645 Details Get a Quote
PRSS27 Knockout HEK293 Cell Line EDJ-KQ9920 Human 83886 Details Get a Quote
PRSS21 Knockout HEK293 Cell Line EDJ-KQ14930 Human 10942 Details Get a Quote
PRSS22 Knockout HEK293 Cell Line EDJ-KQ14931 Human 64063 Details Get a Quote
PRSS22 Knockout HCT 116 Cell Line EDJ-KQ44121 Human 64063 Details Get a Quote
PRSS23 Knockout A-549 Cell Line EDJ-KQ22604 Human 11098 Details Get a Quote
PRSS23 Knockout HCT 116 Cell Line EDJ-KQ22605 Human 11098 Details Get a Quote
PRSS23 Knockout HeLa Cell Line EDJ-KQ22606 Human 11098 Details Get a Quote
PRSS21 Knockout HeLa Cell Line EDJ-KQ45380 Human 10942 Details Get a Quote
PRSS2 Knockout HeLa Cell Line EDJ-KQ54228 Human 5645 Details Get a Quote
PRSS22 Knockout HeLa Cell Line EDJ-KQ57012 Human 64063 Details Get a Quote
PRSS27 Knockout HeLa Cell Line EDJ-KQ57495 Human 83886 Details Get a Quote
PRSS2 Knockout A-549 Cell Line EDJ-KQ62721 Human 5645 Details Get a Quote
PRSS21 Knockout A-549 Cell Line EDJ-KQ64024 Human 10942 Details Get a Quote
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