Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.
Variations in the serine protease 1 (PRSS1) gene encoding human cationic trypsinogen have been conclusively associated with autosomal dominant hereditary pancreatitis and sporadic nonalcoholic chronic pancreatitis. Most high-penetrance PRSS1 variants increase intrapancreatic trypsin activity by stimulating trypsinogen autoactivation and/or by inhibiting chymotrypsin C-dependent trypsinogen degradation. Alternatively, some PRSS1 variants can cause trypsinogen misfolding, which results in intracellular retention and degradation with consequent endoplasmic reticulum stress. However, not all PRSS1 variants are pathogenic, and clinical relevance of rare variants is often difficult to ascertain. Here we review the PRSS1 variants published since 1996 and discuss their functional properties and role in chronic pancreatitis.
Department of Molecular and Cell Biology, Henry M. Goldman School of Dental Medicine, Boston University, Boston, Massachusetts.
Balázs Csaba
BC
Németh
Miklós
M
Sahin-Tóth
D000818:Animals; D006801:Humans; D023421:Models, Animal; D050500:Pancreatitis, Chronic / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D014357:Trypsin / Q000235:genetics* / Q000378:metabolism
C489303:PRSS1 protein, human; D014357:Trypsin