KRT81 Gene – Keratin 81: Function, Mutations, and Disease Associations

KRT81 (Keratin 81) is a protein-coding gene that encodes a type II hair keratin. This intermediate filament protein is a basic (type II) keratin that heteropolymerizes with type I keratins to form hair and nail structures. KRT81 is expressed in the hair cortex and is involved in hair shaft integrity. Mutations in KRT81 are associated with monilethrix, a rare autosomal dominant hair disorder characterized by beaded hair and fragility. The gene is also implicated in various cancers, including breast and lung cancer, where altered expression may contribute to tumor progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

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

• Keratinization (Reactome: R-HSA-6805567)

• Formation of the cornified envelope (Reactome: R-HSA-6809374)

Keratin 81 (KRT81) is a 55.6 kDa type II hair keratin protein composed of 505 amino acids. It contains a central alpha-helical rod domain flanked by non-helical head and tail domains. KRT81 heteropolymerizes with type I hair keratins (e.g., KRT31, KRT35) to form intermediate filaments that provide mechanical strength to hair shafts. The protein is predominantly expressed in the hair cortex and is essential for hair integrity. Mutations in the helix initiation motif cause monilethrix, while aberrant expression is observed in several cancers.