KRT5

The KRT5 gene provides instructions for making a protein called keratin 5. 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 5 is specifically produced in cells called keratinocytes in the outer layer of the skin (the epidermis).

Keratin 5 partners with a similar protein, keratin 14, to form molecules called keratin intermediate filaments. These filaments assemble into strong networks that help attach keratinocytes together and anchor the epidermis to underlying layers of skin. The network of keratin intermediate filaments provides strength and resiliency to the skin and protects it from being damaged by friction and other everyday physical stresses.

Researchers believe that keratin 5 may also play a role in transporting melanosomes, which are cellular structures that produce a pigment called melanin. The transport of these structures into keratinocytes is important for normal skin coloration (pigmentation).

epidermolysis bullosa simplex - caused by mutations in the KRT5 gene

More than 60 mutations in the KRT5 gene have been identified in people with epidermolysis bullosa simplex. Most of these genetic changes alter single protein building blocks (amino acids) used to make keratin 5. The most severe form of epidermolysis bullosa simplex, the Dowling-Meara type, usually results from mutations in regions of the KRT5 gene that are essential for the normal assembly of keratin intermediate filaments. Milder forms of the disorder, including the Weber-Cockayne and Koebner types, are often caused by mutations in less critical regions. Epidermis bullosa simplex with mottled pigmentation typically results from a particular KRT5 mutation. This mutation replaces the amino acid proline with the amino acid leucine at protein position 25 (written as Pro25Leu or P25L).

The KRT5 mutations responsible for epidermolysis bullosa simplex change the structure and function of keratin 5, preventing it from working effectively with keratin 14 and interfering with the assembly of the keratin intermediate filament network. A disruption in this network makes keratinocytes fragile and prone to rupture. Minor trauma to the skin, such as rubbing or scratching, can cause these cells to break down, resulting in the formation of painful, fluid-filled blisters.

other disorders - caused by mutations in the KRT5 gene

At least three KRT5 mutations are responsible for a rare skin disorder called Dowling-Degos disease. This condition is characterized by a net-like (reticulate) pattern of dark skin pigmentation, particularly in the body's folds and creases. Although affected individuals do not experience blistering, they may develop dark bumps or thickened patches of skin on the neck and back. The mutations that cause Dowling-Degos disease lead to the production of an abnormally small, nonfunctional version of keratin 5. Studies suggest that a loss of this protein may disrupt the movement of pigment-carrying melanosomes into keratinocytes, where they are needed for normal skin pigmentation.