FLG gene

The FLG gene provides instructions for making filaggrin, a protein essential for maintaining the skin's protective barrier and hydration.

Normal Function

The FLG gene provides instructions for making a large protein called profilaggrin, which is found in cells that make up the outermost layer of skin (the epidermis). Profilaggrin is cleaved to produce multiple copies of the filaggrin protein, which is important for the structure of the epidermis. The profilaggrin molecule can contain 10, 11, or 12 copies of the filaggrin protein, depending on the genetics of the individual. Further processing of the filaggrin protein produces other molecules that play a role in hydration of the skin.

The epidermis acts as a barrier to help minimize water loss and protect the body from foreign substances, including toxins, bacteria, and substances that can cause allergic reactions (allergens), such as pollen and dust mites. Filaggrin plays an important role in the skin's barrier function. It brings together structural proteins in the outermost skin cells to form tight bundles, flattening and strengthening the cells to create a strong barrier. In addition, processing of filaggrin proteins leads to production of molecules that are part of the skin's "natural moisturizing factor," which helps maintain hydration of the skin. These molecules also maintain the correct acidity (pH) of the skin, which is another important aspect of the barrier.

Health Conditions Related to Genetic Changes

Alopecia areata

MedlinePlus Genetics provides information about Alopecia areata.

Atopic dermatitis

Mutations in the FLG gene are strongly associated with a skin disorder called atopic dermatitis (also known as atopic eczema). This condition is characterized by dry, itchy skin and red rashes. Twenty to 30 percent of people with atopic dermatitis have an FLG gene mutation compared with 8 to 10 percent of the general population without atopic dermatitis.

• Having a mutation in this gene only increases the risk of developing atopic dermatitis; not everyone with an FLG gene mutation will develop the disorder.
• Individuals with a mutation in both copies of the FLG gene are at greater risk of developing atopic dermatitis than those with a mutation in only one copy, and the condition is typically more severe in those with two mutated copies.
• The number of filaggrin proteins produced is also associated with risk; individuals with genetic instructions for producing 10 copies are at greater risk than those with instructions for producing 11 or 12 copies.
• Approximately 40 mutations in the FLG gene have been identified in people with atopic dermatitis. These mutations lead to production of an abnormally short profilaggrin molecule that cannot be cleaved to produce filaggrin proteins.

The resulting shortage of filaggrin can impair the barrier function of the skin and lead to a shortage of natural moisturizing factor, allowing excess water to be lost. Research suggests this impairment contributes to the development of allergic disorders, including asthma, hay fever, and food allergies.

Other disorders

More than 40 FLG gene mutations have been found to cause ichthyosis vulgaris, a skin disorder characterized by dry, scaly skin, particularly during the winter. Affected individuals can also have unusually prominent creases on the palms of their hands and soles of their feet (palmar and plantar hyperlinearity).

• Individuals with a mutation in one copy of the FLG gene are typically mildly affected.
• Individuals with two mutated copies of the gene have more severe symptoms that may be present year-round.
• FLG gene mutations increase the risk of hay fever, food allergies, and skin sensitivity to nickel, regardless of whether the person has atopic dermatitis.

Genomic Location

The FLG gene is found on chromosome 1.