KRT5 gene
The KRT5 gene provides instructions for making keratin 5, a protein essential for the strength and resilience of the skin.
Normal Function
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 produced in cells called keratinocytes in the outer layer of the skin (the epidermis).
Keratin 5 partners with a similar protein, keratin 14 (produced from the KRT14 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 5 interacts with pigment-producing cells called melanocytes to transport melanosomes, which are cellular structures within melanocytes that carry pigment called melanin. The transport of these structures from melanocytes to keratinocytes is important for the development of normal skin coloration (pigmentation).
Health Conditions Related to Genetic Changes
Dowling-Degos disease
At least five mutations in the KRT5 gene have been found to cause Dowling-Degos disease. This condition results in various skin abnormalities, including a characteristic lacy pattern of abnormally dark skin coloring (hyperpigmentation) that occurs mostly in the body's folds and creases. Most KRT5 gene mutations that cause Dowling-Degos disease lead to the production of a keratin 5 protein that is abnormally small and nonfunctional or prevent any protein from being produced from the gene. A shortage (deficiency) of functional keratin 5 impairs the formation of keratin intermediate filaments. Additionally, a deficiency of keratin 5 may disrupt the movement of pigment-carrying melanosomes into keratinocytes, which is thought to cause the pigmentation abnormalities seen in individuals with this disease.
Epidermolysis bullosa simplex
More than 130 mutations in the KRT5 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 mutations alter single protein building blocks (amino acids) used to make keratin 5.
The KRT5 gene mutations responsible for epidermolysis bullosa simplex change the structure and function of keratin 5, preventing it from partnering effectively with keratin 14 and interfering with the assembly of the keratin intermediate filament network. Mutations that cause severe forms of the disorder, such as the Dowling-Meara type, badly 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.
Other Names for This Gene
- 58 kda cytokeratin
- CK5
- cytokeratin 5
- EBS2
- K2C5_HUMAN
- K5
- keratin 5, type II
- keratin, type II cytoskeletal 5
- Keratin-5
- KRT5A