FOXL2 gene

The FOXL2 gene encodes a transcription factor that is critical for the development of the eyelids and the regulation of ovarian function.

Normal Function

The FOXL2 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and helps control the activity of particular genes. On the basis of this role, the FOXL2 protein is called a transcription factor. The protein contains a stretch of repeated alanine amino acids known as a polyalanine tract or poly(A) tract, the function of which is unknown.

The FOXL2 protein is active in multiple tissues, including the eyelids, the ovaries, and the pituitary gland. It is involved in the development of eyelid muscles and regulates the growth and division of hormone-producing ovarian cells called granulosa cells. Additionally, it plays a role in the breakdown of fats, steroid hormones, and reactive oxygen species, as well as in controlled cell death (apoptosis) in the ovaries.

Health Conditions Related to Genetic Changes

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES)

More than 260 mutations in the FOXL2 gene have been found to cause BPES. There are two types of BPES, both involving eyelid abnormalities that prevent them from fully opening. Type I also includes early loss of ovarian function (primary ovarian insufficiency).

• Type II BPES: Generally caused by mutations resulting in a partial loss of FOXL2 protein function, often involving the addition of extra alanines to the poly(A) tract.
• Type I BPES: Often caused by mutations leading to a complete loss of FOXL2 protein function, impairing both eyelid development and ovarian activities.

Approximately 12 percent of mutations causing BPES are deletions of the FOXL2 gene. Some individuals with large deletions may also experience microcephaly, intellectual disability, heart defects, and growth delay.

Other disorders

At least three mutations in the FOXL2 gene are thought to cause primary ovarian insufficiency without eyelid abnormalities. This condition causes menstrual periods to stop before age 40 and can lead to subfertility or infertility.

Cancers

A specific somatic mutation (not inherited) in the FOXL2 gene, known as Cys134Trp or C134W, has been found in adult granulosa cell tumors of the ovary. This mutation interferes with the regulation of granulosa cell proliferation and apoptosis, leading to unregulated cell growth and tumor formation.

Other Names for This Gene

• BPES
• BPES1
• forkhead transcription factor FOXL2
• FOXL2_HUMAN
• PFRK