KRT18 Gene: Keratin 18 Function, Mutations, and Clinical Significance

KRT18 encodes keratin 18, a type I intermediate filament protein that forms heteropolymers with type II keratins (e.g., keratin 8). It is primarily expressed in simple epithelial tissues, including liver, pancreas, intestine, and breast. Keratin 18 provides mechanical stability, regulates cell signaling, and protects cells from apoptosis. Mutations in KRT18 are associated with cryptogenic cirrhosis and susceptibility to liver disease. Altered expression and fragmentation of keratin 18 are biomarkers in non-alcoholic steatohepatitis (NASH) and various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Intermediate filament organization (Reactome: R-HSA-6809371)

• Apoptotic cleavage of cell adhesion proteins (Reactome: R-HSA-351906)

• Keratinization (KEGG: hsa04540)

Keratin 18 (UniProt P05783) is a 48 kDa type I intermediate filament protein composed of a central alpha-helical rod domain flanked by non-helical head and tail domains. It heteropolymerizes with keratin 8 to form filaments that provide mechanical resilience to simple epithelial cells. Post-translational modifications include phosphorylation at Ser33 and Ser52, which regulate filament reorganization during mitosis and apoptosis. Caspase cleavage at Asp238 generates neo-epitopes (M30, M65) used as biomarkers for cell death. The protein also interacts with TRADD and TNFR1 to modulate death receptor signaling.