KRT6C

The KRT6C gene provides instructions for making a protein called keratin 6c or K6c. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, and nails. Keratin 6c is found in the skin, although it is unknown which other tissues may produce this protein.

Keratin 6c is a component of molecules called keratin intermediate filaments. These filaments assemble into dense networks that provide strength and resilience to the skin, nails, and other tissues. Networks of keratin filaments protect these tissues from being damaged by friction and other everyday physical stresses.

focal palmoplantar keratoderma - caused by mutations in the KRT6C gene

At least three KRT6C gene mutations have been found to cause focal palmoplantar keratoderma. This condition causes painful blisters and calluses to develop on the soles of the feet and, less commonly, on the palms of the hands. It is sometimes considered a mild form (variant) of pachyonychia congenita, a related skin disorder that also results from mutations in keratin genes. However, most people with focal palmoplantar keratoderma do not have the severe nail abnormalities or other skin problems that are characteristic of pachyonychia congenita.

One of the mutations associated with focal palmoplantar keratoderma changes a single protein building block (amino acid) in the keratin 6c protein. Specifically, this mutation replaces the amino acid glutamic acid with the amino acid lysine at protein position 472 (written as Glu472Lys or E472K). The other KRT6C gene mutations delete one or more amino acids from the keratin 6c protein.

All of the known KRT6C gene mutations alter the structure of keratin 6c and interfere with the assembly of the keratin intermediate filament network. Skin cells with defective keratin are fragile and prone to damage, making the skin less resistant to friction and minor trauma. The soles of the feet experience a significant amount of friction compared with many other parts of the body and must bear the body's weight, which may help explain why blisters and calluses occur primarily in this area in people with focal palmoplantar keratoderma.