FOXL2

This gene encodes a forkhead transcription factor. The protein contains a fork-head DNA-binding domain and may play a role in ovarian development and function. Expansion of a polyalanine repeat region and other mutations in this gene are a cause of blepharophimosis syndrome and premature ovarian failure 3.

Full Name

FOXL2

Function

Transcriptional regulator. Critical factor essential for ovary differentiation and maintenance, and repression of the genetic program for somatic testis determination. Prevents trans-differentiation of ovary to testis through transcriptional repression of the Sertoli cell-promoting gene SOX9 (By similarity).

Has apoptotic activity in ovarian cells. Suppresses ESR1-mediated transcription of PTGS2/COX2 stimulated by tamoxifen (By similarity).

Is a regulator of CYP19 expression (By similarity).

Participates in SMAD3-dependent transcription of FST via the intronic SMAD-binding element (By similarity).

Is a transcriptional repressor of STAR. Activates SIRT1 transcription under cellular stress conditions. Activates transcription of OSR2.

Biological Process

Anatomical structure morphogenesis Source: GO_Central
Apoptotic DNA fragmentation Source: UniProtKB
Cell differentiation Source: GO_Central
Extraocular skeletal muscle development Source: UniProtKB
Negative regulation of transcription, DNA-templated Source: UniProtKB
Ovarian follicle development Source: UniProtKB
Positive regulation of apoptotic process Source: UniProtKB
Positive regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
Positive regulation of transcription, DNA-templated Source: UniProtKB
Regulation of transcription by RNA polymerase II Source: GO_Central

Cellular Location

Nucleus

Involvement in disease

Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES):
A disorder characterized by eyelid dysplasia, small palpebral fissures, drooping eyelids and a skin fold curving in the mediolateral direction, inferior to the inner canthus. In type I BPSE (BPES1) eyelid abnormalities are associated with female infertility. Affected females show an ovarian deficit due to primary amenorrhea or to premature ovarian failure (POF). In type II BPSE (BPES2) affected individuals show only the eyelid defects.
Premature ovarian failure 3 (POF3):
An ovarian disorder defined as the cessation of ovarian function under the age of 40 years. It is characterized by oligomenorrhea or amenorrhea, in the presence of elevated levels of serum gonadotropins and low estradiol.

PTM

Sumoylated with SUMO1; sumoylation is required for transcriptional repression activity.