CAPN14 Gene - Calpain 14: Function, Mutations, and Disease Association

CAPN14 encodes calpain 14, a member of the calpain family of calcium-dependent cysteine proteases. This enzyme is specifically expressed in the esophageal epithelium and plays a critical role in maintaining epithelial barrier integrity. CAPN14 is involved in the regulation of desmosomal proteins and tight junctions, and its dysfunction is strongly associated with eosinophilic esophagitis (EoE), an allergic inflammatory condition. Genetic variants in CAPN14 have been linked to increased risk of EoE, particularly in individuals with atopic predisposition.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Calpain-mediated proteolysis of desmosomal proteins (e.g.

• desmoglein-1)

• Epithelial barrier integrity pathway

• Eosinophilic esophagitis susceptibility pathway

Calpain 14 is a 726-amino acid calcium-dependent cysteine protease with a typical calpain domain architecture: an N-terminal anchor domain, a catalytic cysteine protease domain (CysPc), and a C-terminal calpain-type beta-sandwich domain. It is highly expressed in the esophageal epithelium, where it localizes to desmosomes and cleaves desmoglein-1 and other desmosomal cadherins, regulating cell-cell adhesion and barrier function. Dysregulation of CAPN14 leads to increased epithelial permeability and allergen sensitization, central to the pathogenesis of eosinophilic esophagitis.