Comprehensive functional analysis of chymotrypsin C ( <i>CTRC</i> ) variants reveals distinct loss-of-function mechanisms associated with pancreatitis risk

Abstract

Pathogenic CTRC variants cause loss of function by three distinct but mutually non-exclusive mechanisms that affect secretion, activity and proteolytic stability. ER stress may be induced by a subset of CTRC mutants, but does not represent a common pathological mechanism of CTRC variants. This phenotypic dataset should aid in the classification of the clinical relevance of CTRC variants identified in patients with chronic pancreatitis.