KRT16

The KRT16 gene provides instructions for making a protein called keratin 16 or K16. Keratins are a group of tough, fibrous proteins that form the structural framework of certain cells, particularly cells that make up the skin, hair, nails, and similar tissues. Keratin 16 is produced in the nails, the skin on the palms of the hands and soles of the feet, and the oral mucosa that lines the inside of the mouth. It has also been found in specialized pigment cells called melanocytes, although its function in these cells is unknown.

Keratin 16 partners with a similar protein, keratin 6a, to form molecules called keratin intermediate filaments. These filaments assemble into dense networks that provide strength and resiliency to the skin, nails, and other tissues. Networks of keratin filaments protect these tissues from being damaged by friction and other everyday physical stresses. Keratin 16 is also among several keratins involved in wound healing.

pachyonychia congenita - caused by mutations in the KRT16 gene

At least 13 mutations in the KRT16 gene have been identified in people with pachyonychia congenita type 1 (PC-1). In most cases, this condition becomes apparent within the first few months of life, but KRT16 mutations are also associated with a rare form of the disorder (pachyonychia congenita tarda) that appears in adolescence or early adulthood. Most of the KRT16 mutations associated with pachyonychia congenita change single protein building blocks (amino acids) in keratin 16. A few mutations delete a small number of amino acids from the protein.

The KRT16 mutations responsible for pachyonychia congenita change the structure of keratin 16, preventing it from working effectively with keratin 6a and interfering with the assembly of the keratin intermediate filament network. Without this network, skin cells become fragile and are easily damaged, making the skin less resistant to friction and minor trauma. Even normal activities such as walking can cause skin cells to break down, resulting in the formation of painful blisters and calluses. Additionally, fragile skin cells may abnormally produce more keratin in response to damage, which makes the skin problems worse.

Defective keratin 16 also disrupts the growth and function of cells in the nails and oral mucosa, which explains why the signs and symptoms of pachyonychia congenita also affect these tissues.

other disorders - caused by mutations in the KRT16 gene

Several mutations in the KRT16 gene have been found to cause a skin disorder called focal non-epidermolytic palmoplantar keratoderma (FNEPPK). This condition is similar to pachyonychia congenita, and it is often described as a mild variant of that disorder. People with FNEPPK develop painful calluses and blisters on the skin. The blistering is most severe in weight-bearing areas, such as the soles of the feet, and in other areas that experience trauma or friction. Most people with FNEPPK do not have the significant fingernail abnormalities that are characteristic of pachyonychia congenita.

Like the KRT16 mutations that cause pachyonychia congenita, the mutations that underlie FNEPPK 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.