*4.2.1 PRSS1 and PRSS2*

Hereditary pancreatitis (HP) is a specific subtype of CP. The mutations in the human cationic trypsinogen (PRSS1) can cause the premature activation of the trypsinogen in various ways. 90% percent of the HP patients diagnosed with PRSS1 mutation carry one of the 3 mutations: p.N29I, p.R122C, or p.R122H in the heterozygous state. The p.N29I variant causes an increase in N-terminal processing, decreased CTRC -dependent degradation, and an increased propensity for autoactivation of the trypsin. The p.R122C and p.R122H mutations mainly prevent CTRC-mediated trypsinogen degradation [27–29].

There is no pathologic variants of human anionic trypsinogen (PRSS2) found in patients with CP. Even Genome wide association studies (GWASs) have identified a protective PRSS2 locus that slightly decreases CP risk, with a more pronounced effect in alcoholic [30].
