Gene: PRSS1

Alternate names for this Gene: TRP1|TRY1|TRY4|TRYP1

Gene Summary: This gene encodes a trypsinogen, which is a member of the trypsin family of serine proteases. This enzyme is secreted by the pancreas and cleaved to its active form in the small intestine. It is active on peptide linkages involving the carboxyl group of lysine or arginine. Mutations in this gene are associated with hereditary pancreatitis. This gene and several other trypsinogen genes are localized to the T cell receptor beta locus on chromosome 7.

Gene is located in Chromosome: 7

Location in Chromosome : 7q34

Description of this Gene: serine protease 1

Type of Gene: protein-coding

rs111033564 in PRSS1 gene and Hereditary pancreatitis PMID 11788572 2002 Novel cationic trypsinogen (PRSS1) N29T and R122C mutations cause autosomal dominant hereditary pancreatitis.

PMID 10204851 1999 Mutations in the cationic trypsinogen gene and evidence for genetic heterogeneity in hereditary pancreatitis.

PMID 10381903 1999 A signal peptide cleavage site mutation in the cationic trypsinogen gene is strongly associated with chronic pancreatitis.

PMID 10930381 2000 Chronic pancreatitis associated with an activation peptide mutation that facilitates trypsin activation.

PMID 11866271 2002 Mutational screening of patients with nonalcoholic chronic pancreatitis: identification of further trypsinogen variants.

PMID 11073545 2000 A CGC>CAT gene conversion-like event resulting in the R122H mutation in the cationic trypsinogen gene and its implication in the genotyping of pancreatitis.

PMID 9633818 1998 Mutations of the cationic trypsinogen in hereditary pancreatitis.

PMID 14695529 2004 To challenge this notion, here we describe the unique properties of the E79K cationic trypsinogen mutation (c.235G>A), which was identified in three European families affected by sporadic or familial pancreatitis cases.

PMID 8841182 1996 Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene.

PMID 9322498 1997 Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis.

PMID 15776435 2005 Gene conversion between functional trypsinogen genes PRSS1 and PRSS2 associated with chronic pancreatitis in a six-year-old girl.

PMID 11748242 2002 Human cationic trypsinogen. Arg(117) is the reactive site of an inhibitory surface loop that controls spontaneous zymogen activation.

PMID 19453252 2009 Chronic pancreatitis: genetics and pathogenesis.

PMID 11097832 2000 Gain-of-function mutations associated with hereditary pancreatitis enhance autoactivation of human cationic trypsinogen.

PMID 18755888 2009 The natural history of hereditary pancreatitis: a national series.

PMID 15028953 2004 Based on these findings, we revised the criteria for the diagnosis of HP; (1) recurrent acute or chronic pancreatitis with R122H or N29I mutation of the CT gene, or (2) recurrent acute or chronic pancreatitis with a family history of 2 or more affected patients, irrespective of generation, with at least 1 of the patients having no known etiological factors, and in case of siblings only, the onset of the disease in at least 1 of the patients is under age 40 years.

PMID 21415673 2011 High incidence of PRSS1 and SPINK1 mutations in Korean children with acute recurrent and chronic pancreatitis.

PMID 11788572 2002 Hereditary pancreatitis (HP) is usually caused by mutations in the cationic trypsinogen (PRSS1) gene, especially R122H or N29I.

PMID 14695529 2004 Interaction between trypsinogen isoforms in genetically determined pancreatitis: mutation E79K in cationic trypsin (PRSS1) causes increased transactivation of anionic trypsinogen (PRSS2).

PMID 24002981 2013 Comprehensive screening for PRSS1, SPINK1, CFTR, CTRC and CLDN2 gene mutations in Chinese paediatric patients with idiopathic chronic pancreatitis: a cohort study.

PMID 11097832 2000 Here we demonstrate that the two most frequent HP mutations, Arg117 --> His and Asn21 --> Ile, significantly enhance autoactivation of human cationic trypsinogen in vitro, in a manner that correlates with the severity of clinical symptoms in HP.

PMID 22539344 2012 We found that in the presence of CTRC, trypsinogen mutants associated with classic hereditary pancreatitis (N29I, N29T, V39A, R122C, and R122H) autoactivated at increased rates and reached markedly higher active trypsin levels compared with wild-type cationic trypsinogen.

PMID 10872414 2000 Risk factors for cancer in hereditary pancreatitis. International Hereditary Pancreatitis Study Group.

PMID 16632094 2006 Biochemical models of hereditary pancreatitis.

PMID 10801865 2000 Instead, an increased propensity to autoactivation under acidic conditions might be relevant to the pathomechanism of the Asn-21 --> Ile mutation in hereditary pancreatitis.

PMID 25383785 2015 One-third (34%) of patients with ARP carry mutations for hereditary pancreatitis including rare mutations (K23R), and 12.5% have evidence of cftr mutations and 10% had CFTR dysfunction underscoring the importance of genetic and functional workup of these patients.

PMID 16036133 2005 Expression of mutated cationic trypsinogen reduces cellular viability in AR4-2J cells.

PMID 23601753 2013 We conclude that D19A, D22G, K23R and K23_I24insIDK form a mechanistically distinct subset of hereditary pancreatitis-associated mutations that exert their effect primarily through direct stimulation of autoactivation, independently of CTRC.

PMID 30420730 2018 SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

PMID 17568390 2007 Functional analysis of pancreatitis-associated missense mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene.

PMID 22539344 2012 We found that in the presence of CTRC, trypsinogen mutants associated with classic hereditary pancreatitis (N29I, N29T, V39A, R122C, and R122H) autoactivated at increased rates and reached markedly higher active trypsin levels compared with wild-type cationic trypsinogen.

PMID 17204147 2007 Hereditary chronic pancreatitis.

PMID 16954950 2006 Analysis of CFTR, SPINK1, PRSS1 and AAT mutations in children with acute or chronic pancreatitis.

PMID 19454815 2009 Hereditary pancreatitis: clinical features and inheritance characteristics of the R122C mutation in the cationic trypsinogen gene (PRSS1) in six Spanish families.

PMID 24458023 2014 Human cationic trypsinogen (PRSS1) variants and chronic pancreatitis.

PMID 18272034 2008 Novel mutation and polymorphism of PRSS1 gene in the Chinese patients with hereditary pancreatitis and chronic pancreatitis.

PMID 11719509 2002 Here we report a family with hereditary pancreatitis that carries a novel PRSS1 mutation (R122C).

PMID 11734061 2001 Discrimination of three mutational events that result in a disruption of the R122 primary autolysis site of the human cationic trypsinogen (PRSS1) by denaturing high performance liquid chromatography.

PMID 16791840 2006 Mutations of human cationic trypsinogen (PRSS1) and chronic pancreatitis.

PMID 24780743 2015 The PRSS1 c.623G>C (p.G208A) mutation is the most common PRSS1 mutation in Korean children with hereditary pancreatitis.

PMID 23455445 2014 Functional effects of 13 rare PRSS1 variants presumed to cause chronic pancreatitis.

PMID 17003641 2006 Identification of CFTR, PRSS1, and SPINK1 mutations in 381 patients with pancreatitis.

PMID 24413785 2014 Chronic pancreatitis associated with the p.G208A variant of PRSS1 gene in a European patient.

PMID 23686146 2014 PRSS1 c.623G>C (p.G208A) variant is associated with pancreatitis in Japan.

PMID 22539344 2012 Increased activation of hereditary pancreatitis-associated human cationic trypsinogen mutants in presence of chymotrypsin C.

PMID 22749696 2012 Genetics and pathogenesis of chronic pancreatitis: the 2012 update.

PMID 19951905 2010 Ten families with p.A16V mutations were identified (22 affected individuals): six HP families, three with idiopathic disease and one with only a single generation affected.

PMID 20502448 2010 Among HP patients, no p.N29I mutations were found and the p.A16V mutation was more frequent than previously reported, 45 and 32% had exocrine and endocrine insufficiency, respectively, and among tIP patients 9 and 12%, respectively.

PMID 10381903 1999 Heterozygosity for the A16V mutation is strongly associated with CP.

PMID 21907651 2012 An overview of hereditary pancreatitis.

PMID 16505482 2006 Chymotrypsin C (caldecrin) stimulates autoactivation of human cationic trypsinogen.

PMID 11260229 2001 Among the known PRSS1 mutations, only the R122H was detected in a single subject and the A16V in two subjects in the cohort, strengthening that HP-associated PRSS1 mutations are rare in ICP.

PMID 15017610 2004 Clinical and genetic characteristics of hereditary pancreatitis in Europe.

PMID 11866271 2002 The mutation R122H of the cationic trypsinogen was found in 21 index patients, N291 in six index patients, and A16V and D22G in one index patient, all from HP families.

PMID 11866271 2002 The mutation R122H of the cationic trypsinogen was found in 21 index patients, N291 in six index patients, and A16V and D22G in one index patient, all from HP families.

PMID 11788572 2002 Hereditary pancreatitis (HP) is usually caused by mutations in the cationic trypsinogen (PRSS1) gene, especially R122H or N29I.

rs10273639 in PRSS1 gene and Malignant Neoplasms PMID 29299148 2017 Cancer risk susceptibility loci in a Swedish population.

rs1964986 in PRSS1 gene and Neuroblastoma PMID 19536264 2009 Copy number variation at 1q21.1 associated with neuroblastoma.

rs10273639 in PRSS1 gene and Pancreatitis PMID 23143602 2012 Common genetic variants in the CLDN2 and PRSS1-PRSS2 loci alter risk for alcohol-related and sporadic pancreatitis.

rs3857776 in PRSS1 gene and Pancreatitis, Alcoholic PMID 28754779 2018 Genome-wide association study identifies inversion in the CTRB1-CTRB2 locus to modify risk for alcoholic and non-alcoholic chronic pancreatitis.