KRT10

The KRT10 gene provides instructions for making a protein called keratin 10. Keratins are a group of tough, fibrous proteins that form the structural framework of cells called keratinocytes that make up the skin, hair, and nails. Keratin 10 is produced in keratinocytes in the outer layer of the skin (the epidermis).

The keratin 10 protein partners with a similar protein, keratin 1 (produced from the KRT1 gene), to form molecules called keratin intermediate filaments. These filaments assemble into strong networks that provide strength and resiliency to the skin and protect it from being damaged by friction and other everyday physical stresses.

epidermolytic hyperkeratosis - caused by mutations in the KRT10 gene

Dozens of mutations in the KRT10 gene have been found in people with epidermolytic hyperkeratosis. This condition is characterized by red, blistering skin at an early age and thick skin (hyperkeratosis) later in life. People with KRT10 gene mutations typically have NPS-type epidermolytic hyperkeratosis, which features thick skin on many parts of the body but not the palms of the hands or soles of the feet.

Most KRT10 gene mutations associated with epidermolytic hyperkeratosis change a single protein building block (amino acid) in the keratin 10 protein. These amino acid changes commonly occur in regions of the protein that play a role in intermediate filament formation. The mutations alter the keratin 10 protein and seem to affect how intermediate filaments interact with each other to form networks. The altered proteins still form intermediate filaments, but the intermediate filament networks are weaker and do not function normally. Without a strong network, skin cells become fragile and are easily damaged, which can lead to blistering in response to friction or mild trauma. It is unclear how these mutations cause the overgrowth of keratinocytes that results in hyperkeratotic skin.

other disorders - caused by mutations in the KRT10 gene

Mutations in the KRT10 gene are involved in other skin disorders. One disorder, cyclic ichthyosis with epidermolytic hyperkeratosis, is similar to epidermolytic hyperkeratosis, but the skin changes disappear for short periods, then recur. The recurrent skin changes can last for weeks or months. Another condition, congenital reticular ichthyosiform erythroderma (also called ichthyosis with confetti), is characterized by red, scaly skin all over the body with patches of normal skin that look like confetti. The patches of normal skin increase in number and size with age.