KRT17

The KRT17 gene provides instructions for making a protein called keratin 17 or K17. 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 17 is produced in the nails, the hair follicles, and the skin on the palms of the hands and soles of the feet. It is also found in the skin's sebaceous glands, which produce an oily substance called sebum.

Keratin 17 partners with a similar protein, keratin 6b, 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 17 is also among several keratins involved in wound healing.

pachyonychia congenita - caused by mutations in the KRT17 gene

At least 16 mutations in the KRT17 gene have been identified in people with pachyonychia congenita type 2 (PC-2). In most cases, this condition becomes apparent within the first few months of life, but KRT17 mutations are also associated with a rare form of the disorder (pachyonychia congenita tarda) that appears in adolescence or early adulthood. Most of the KRT17 mutations associated with pachyonychia congenita change a single protein building block (amino acid) in keratin 17.

The KRT17 mutations responsible for pachyonychia congenita change the structure of keratin 17, preventing it from working effectively with keratin 6b 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. In the sebaceous glands, abnormal keratin filaments lead to the development of cysts called steatocystomas. Defective keratin 17 also disrupts the growth and function of cells in the nails and hair follicles, which explains why the signs and symptoms of pachyonychia congenita also affect these tissues.

other disorders - caused by mutations in the KRT17 gene

Several mutations in the KRT17 gene have been found to cause a skin disorder called hereditary steatocystoma multiplex. Researchers suggest that this condition may be a mild variant of PC-2. Like PC-2, hereditary steatocystoma multiplex is characterized by the development of multiple sebaceous gland cysts called steatocystomas. Most people with hereditary steatocystoma multiplex do not have the other features of PC-2, although mild nail abnormalities are possible.

The KRT17 mutations responsible for hereditary steatocystoma multiplex interfere with the assembly of the keratin intermediate filament network. It is unclear why steatocystomas are typically the only feature of this disorder.