KRT6B

The KRT6B gene provides instructions for making a protein called keratin 6b or K6b. 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 6b 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 6b partners with a similar protein, keratin 17, 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 6b is also among several keratins involved in wound healing.

pachyonychia congenita - caused by mutations in the KRT6B gene

At least two mutations in the KRT6B gene have been identified in people with pachyonychia congenita type 2 (PC-2). One of these mutations changes a single protein building block (amino acid) in keratin 6b, while the other mutation deletes an amino acid from the protein.

The KRT6B mutations responsible for PC-2 change the structure of keratin 6b, preventing it from working effectively with keratin 17 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 6b also disrupts the growth and function of cells in the nails and hair follicles, which explains why the signs and symptoms of PC-2 also affect these tissues.