FOXL2

Reviewed November 2008

What is the official name of the FOXL2 gene?

The official name of this gene is “forkhead box L2.”

FOXL2 is the gene's official symbol. The FOXL2 gene is also known by other names, listed below.

What is the normal function of the FOXL2 gene?

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 FOXL2 protein is active in the developing eyelids and ovaries before birth. This protein also plays a role in the maintenance of the ovaries throughout adult life. The specific function of the FOXL2 protein is unknown, but it is thought to be involved in many regulatory functions within cells.

The FOXL2 protein contains one area where a protein building block (amino acid) called alanine is repeated multiple times. This stretch of alanines is known as a polyalanine tract or poly(A) tract.

Does the FOXL2 gene share characteristics with other genes?

The FOXL2 gene belongs to a family of genes called FOX (forkhead box genes).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the FOXL2 gene related to health conditions?

blepharophimosis, ptosis, and epicanthus inversus syndrome - caused by mutations in the FOXL2 gene

More than 130 mutations in the FOXL2 gene have been found to cause blepharophimosis, ptosis, and epicanthus inversus syndrome (also called BPES). Mutations that lead to a significantly shortened FOXL2 protein often cause BPES type I, which is characterized by eyelid malformations and premature ovarian failure. Premature ovarian failure causes a woman's menstrual periods to become less frequent and eventually stop before age 40. Premature ovarian failure can lead to difficultly conceiving a child (subfertiliy) or a complete inability to conceive (infertility). Mutations that result in an extra long FOXL2 protein may cause BPES type II, which involves only eyelid malformations. A common mutation in people with BPES adds alanines to the polyalanine tract in the FOXL2 protein. These extra alanines cause the FOXL2 protein to be abnormally long and functionally impaired.

The majority of mutations that cause BPES occur within the FOXL2 gene; however, some disease-causing mutations occur in a neighboring region of DNA that normally regulates the activity of the FOXL2 gene, known as a regulatory region. It is estimated that about 5 percent of people with BPES have a mutation in a regulatory region outside the FOXL2 gene.

Some people with BPES have large DNA deletions that remove not only the FOXL2 gene but one or more neighboring genes. Individuals with these large DNA deletions have the signs and symptoms of BPES, but they can also have other features. The combination of additional features depends on which genes are included in the deletion, but can include an unusually small head (microcephaly), intellectual disability, heart defects, and growth delay.

Where is the FOXL2 gene located?

Cytogenetic Location: 3q23

Molecular Location on chromosome 3: base pairs 138,663,065 to 138,665,981

The FOXL2 gene is located on the long (q) arm of chromosome 3 at position 23.

More precisely, the FOXL2 gene is located from base pair 138,663,065 to base pair 138,665,981 on chromosome 3.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about FOXL2?

You and your healthcare professional may find the following resources about FOXL2 helpful.

Educational resources - Information pages
Developmental Biology (sixth edition, 2000): Transcription Factors (http://www.ncbi.nlm.nih.gov/books/NBK10023/)
Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/books/NBK1441/)
Genetic Testing Registry - Repository of genetic test information
- GTR: Genetic tests for FOXL2 (http://www.ncbi.nlm.nih.gov/gtr/tests/?term=668%5Bgeneid%5D)

You may also be interested in these resources, which are designed for genetics professionals and researchers.

PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(FOXL2%5BTIAB%5D)%20AND%20((Genes%5BMH%5D)%20OR%20(Genetic%20Phenomena%5BMH%5D))%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%201800%20days%22%5Bdp%5D)
OMIM - Genetic disorder catalog (http://omim.org/entry/605597)
Research Resources - Tools for researchers
- Atlas of Genetics and Cytogenetics in Oncology and Haematology (http://atlasgeneticsoncology.org/Genes/GC_FOXL2.html)
- Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/668)
- GeneCards (http://www.genecards.org/cgi-bin/carddisp.pl?id_type=entrezgene&id=668)
- HUGO Gene Nomenclature Committee (http://www.genenames.org/data/hgnc_data.php?hgnc_id=1092)

What other names do people use for the FOXL2 gene or gene products?

BPES
BPES1
forkhead transcription factor FOXL2
FOXL2_HUMAN
PFRK

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FOXL2?

amino acid ; blepharophimosis ; deletion ; DNA ; gene ; infertility ; microcephaly ; mutation ; ovarian ; protein ; ptosis ; syndrome ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

Beysen D, De Jaegere S, Amor D, Bouchard P, Christin-Maitre S, Fellous M, Touraine P, Grix AW, Hennekam R, Meire F, Oyen N, Wilson LC, Barel D, Clayton-Smith J, de Ravel T, Decock C, Delbeke P, Ensenauer R, Ebinger F, Gillessen-Kaesbach G, Hendriks Y, Kimonis V, Laframboise R, Laissue P, Leppig K, Leroy BP, Miller DT, Mowat D, Neumann L, Plomp A, Van Regemorter N, Wieczorek D, Veitia RA, De Paepe A, De Baere E. Identification of 34 novel and 56 known FOXL2 mutations in patients with Blepharophimosis syndrome. Hum Mutat. 2008 Nov;29(11):E205-19. doi: 10.1002/humu.20819. (http://www.ncbi.nlm.nih.gov/pubmed/18642388?dopt=Abstract)
Beysen D, De Paepe A, De Baere E. FOXL2 mutations and genomic rearrangements in BPES. Hum Mutat. 2009 Feb;30(2):158-69. doi: 10.1002/humu.20807. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18726931?dopt=Abstract)
Beysen D, Raes J, Leroy BP, Lucassen A, Yates JR, Clayton-Smith J, Ilyina H, Brooks SS, Christin-Maitre S, Fellous M, Fryns JP, Kim JR, Lapunzina P, Lemyre E, Meire F, Messiaen LM, Oley C, Splitt M, Thomson J, Van de Peer Y, Veitia RA, De Paepe A, De Baere E. Deletions involving long-range conserved nongenic sequences upstream and downstream of FOXL2 as a novel disease-causing mechanism in blepharophimosis syndrome. Am J Hum Genet. 2005 Aug;77(2):205-18. Epub 2005 Jun 16. (http://www.ncbi.nlm.nih.gov/pubmed/15962237?dopt=Abstract)
de Ru MH, Gille JJ, Nieuwint AW, Bijlsma JB, van der Blij JF, van Hagen JM. Interstitial deletion in 3q in a patient with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and microcephaly, mild mental retardation and growth delay: clinical report and review of the literature. Am J Med Genet A. 2005 Aug 15;137(1):81-7. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16015581?dopt=Abstract)
Entrez Gene (http://www.ncbi.nlm.nih.gov/gene/668)
Moumné L, Batista F, Benayoun BA, Nallathambi J, Fellous M, Sundaresan P, Veitia RA. The mutations and potential targets of the forkhead transcription factor FOXL2. Mol Cell Endocrinol. 2008 Jan 30;282(1-2):2-11. Epub 2007 Nov 19. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18155828?dopt=Abstract)
OMIM: FORKHEAD TRANSCRIPTION FACTOR FOXL2 (http://omim.org/entry/605597)

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.