Genes in the KRT family provide instructions for making proteins called keratins. Keratins are a group of tough, fibrous proteins that form the structural framework of epithelial cells, which are cells that line the surfaces and cavities of the body. Epithelial cells make up tissues such as the hair, skin, and nails. These cells also line the internal organs and are an important part of many glands.
Keratins are best known for providing strength and resilience to cells that form the hair, skin, and nails. These proteins allow tissues to resist damage from friction and minor trauma, such as rubbing and scratching. Keratins are also involved in several other critical cell functions, including cell movement (migration), regulation of cell size, cell growth and division (proliferation), wound healing, and transport of materials within cells.
Humans have at least 54 functional keratin genes, which are divided into type I and type II keratins. Most of the type I keratin genes, designated KRT9 through KRT20, are located in a cluster on chromosome 17. The type II keratin genes, designated KRT1 through KRT8, are found in another cluster on chromosome 12.
Different combinations of keratin proteins are found in different tissues. In each tissue, a type I keratin pairs with a type II keratin to form a structure called a heterodimer. Heterodimers interact with one another to form strong, flexible fibers called keratin intermediate filaments. These filaments assemble into a dense network, which forms the structural framework of cells.
Mutations in at least 20 KRT genes have been found to cause human diseases affecting the skin, hair, nails, and related tissues. The most well-studied of these diseases include epidermolysis bullosa simplex (EBS) and pachyonychia congenita. Mutations in KRT genes alter the structure of keratins, which prevent them from forming an effective network of keratin intermediate filaments. Without this network, cells become fragile and are easily damaged, making tissues 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.