FOXC1

The FOXC1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this action, the FOXC1 protein is called a transcription factor.

The FOXC1 protein plays a critical role in early development, particularly in the formation of structures in the front part of the eye (the anterior segment). These structures include the colored part of the eye (the iris), the central hole in the iris through which light enters the eye (the pupil), and the clear front covering of the eye (the cornea). Studies suggest that the FOXC1 protein may also have functions in the adult eye, such as helping cells respond to oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells.

The FOXC1 protein is also involved in the normal development of other parts of the body, including the heart, kidneys, and brain.

Axenfeld-Rieger syndrome - caused by mutations in the FOXC1 gene

More than 50 mutations in the FOXC1 gene have been found to cause Axenfeld-Rieger syndrome type 3, a condition that primarily affects the development of the anterior segment of the eye but can also affect other parts of the body. Many FOXC1 gene mutations reduce the amount of functional FOXC1 protein that is produced or result in a defective protein that cannot regulate the activity of other genes. Other genetic changes (such as a duplication of the FOXC1 gene) likely increase the amount or function of the FOXC1 protein. Having either too little or too much activity of this protein disrupts the regulation of other genes needed for normal development.

Changes in the amount or function of the FOXC1 protein impairs the development of the anterior segment of the eye, leading to the eye abnormalities characteristic of Axenfeld-Rieger syndrome. In some cases, changes involving the FOXC1 protein also cause problems with development of other parts of the body.

other disorders - caused by mutations in the FOXC1 gene

Mutations in the FOXC1 gene have also been identified in rare cases of several other eye disorders. Like Axenfeld-Rieger syndrome, these conditions primarily involve the anterior segment of the eye. They include Peters anomaly, which is a developmental condition characterized by thinning and clouding of the cornea, and iridogoniodysgenesis type 1, a condition associated with underdevelopment of the iris and an elevated risk of increased pressure in the eye (glaucoma).

FOXC1 gene mutations have been reported in a few people with abnormalities of brain development. Mutations that change single protein building blocks (amino acids) in the FOXC1 protein have been associated with defects of the cerebellum, which is the part of the brain that is involved in coordinating movement. Additionally, deletions of genetic material from a region of chromosome 6 that includes the FOXC1 gene and several neighboring genes have been associated with a structural abnormality of the cerebellum known as Dandy-Walker malformation.

Genetics Home Reference provides information about Dandy-Walker syndrome, which is also associated with changes in the FOXC1 gene.