KRT14

The KRT14 gene provides instructions for making a protein called keratin 14. 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 14 is specifically produced in cells called keratinocytes in the outer layer of the skin (the epidermis).

Keratin 14 partners with a similar protein, keratin 5 (produced from the KRT5 gene), 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 14 may also play a role in the formation of sweat glands and the development of patterned ridges on the skin of the hands and feet. These ridges, called dermatoglyphs, are the basis for each person's unique fingerprints.

epidermolysis bullosa simplex - caused by mutations in the KRT14 gene

More than 60 mutations in the KRT14 gene have been identified in people with epidermolysis bullosa simplex, a condition that causes the skin to be very fragile and to blister easily. Most of these genetic changes alter single protein building blocks (amino acids) used to make keratin 14. The most severe form of epidermolysis bullosa simplex, the Dowling-Meara type, usually results from changes in regions of keratin 14 that are essential for the normal assembly of keratin intermediate filaments. Milder forms of the disorder, including the localized type (formerly called the Weber-Cockayne type) and a form known as the other generalized type (formerly called the Koebner type), are often caused by changes affecting less critical regions of the protein.

KRT14 gene mutations change the structure and function of keratin 14, preventing it from working effectively with keratin 5 and interfering with the assembly of the keratin intermediate filament network. Mutations that cause severe forms of the disorder severely disrupt the assembly of keratin intermediate filaments, while mutations that result in milder forms impair keratin filament assembly to a lesser degree. 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.

Naegeli-Franceschetti-Jadassohn syndrome/dermatopathia pigmentosa reticularis - caused by mutations in the KRT14 gene

At least three mutations in the KRT14 gene have been found to cause Naegeli-Franceschetti-Jadassohn syndrome. This rare form of ectodermal dysplasia is characterized by skin and nail abnormalities similar to those seen with dermatopathia pigmentosa reticularis (described above) but does not affect the hair. Some researchers believe these two closely related conditions represent different forms of the same disorder.

The KRT14 gene mutations that cause Naegeli-Franceschetti-Jadassohn syndrome most likely reduce the amount of functional keratin 14 in keratinocytes. Without enough of this protein, keratin intermediate filaments are unable to assemble into a strong, stable network. Abnormal keratin intermediate filaments alter the development and structure of ectodermal tissues, which likely underlies most of the skin and nail problems characteristic of this condition. However, it is unclear how a reduced amount of keratin 14 is related to reticulate hyperpigmentation, which is also seen with this disorder.