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Genetics Home Reference: your guide to understanding genetic conditions
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FOXC2

Reviewed February 2008

What is the official name of the FOXC2 gene?

The official name of this gene is “forkhead box C2 (MFH-1, mesenchyme forkhead 1).”

FOXC2 is the gene's official symbol. The FOXC2 gene is also known by other names, listed below.

What is the normal function of the FOXC2 gene?

The FOXC2 gene provides instructions for making a protein that plays a critical role in the formation of many organs and tissues before birth. This protein is a transcription factor, which means that it attaches (binds) to specific regions of DNA and helps control the activity of many other genes. Researchers believe that the FOXC2 protein has a role in a variety of developmental processes, such as the formation of veins and the development of the lungs, eyes, kidneys and urinary tract, cardiovascular system, and the transport system for immune cells (lymphatic vessels).

Does the FOXC2 gene share characteristics with other genes?

The FOXC2 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 FOXC2 gene related to health conditions?

lymphedema-distichiasis syndrome - caused by mutations in the FOXC2 gene

More than 50 mutations in the FOXC2 gene can cause lymphedema-distichiasis syndrome. Most of these mutations insert or delete a few DNA building blocks (nucleotides), which results in a premature stop signal in the instructions for making the FOXC2 protein. These mutations lead to the production of a FOXC2 protein that is abnormally small and cannot effectively attach (bind) to DNA. As a result, the altered protein cannot regulate the activity of other genes. Other mutations change one protein building block (amino acid) in the area of the FOXC2 protein that binds to DNA, preventing the protein from regulating gene activity. It is not clear why mutations in the FOXC2 gene affect the development of the eye area and lymphatic vessels, the primary regions of the body affected by lymphedema-distichiasis syndrome.

Where is the FOXC2 gene located?

Cytogenetic Location: 16q24.1

Molecular Location on chromosome 16: base pairs 86,567,250 to 86,568,932

The FOXC2 gene is located on the long (q) arm of chromosome 16 at position 24.1.

The FOXC2 gene is located on the long (q) arm of chromosome 16 at position 24.1.

More precisely, the FOXC2 gene is located from base pair 86,567,250 to base pair 86,568,932 on chromosome 16.

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 FOXC2?

You and your healthcare professional may find the following resources about FOXC2 helpful.

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

What other names do people use for the FOXC2 gene or gene products?

  • FKHL14
  • forkhead box C2
  • forkhead, Drosophila, homolog-like 14
  • forkhead (Drosophila)-like 14
  • FOXC2_HUMAN
  • LD
  • MFH1
  • MFH-1
  • MFH-1,mesenchyme forkhead 1

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 FOXC2?

amino acid ; cardiovascular ; DNA ; gene ; lymphedema ; protein ; syndrome ; transcription ; transcription factor ; veins

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

References

  • Berry FB, Tamimi Y, Carle MV, Lehmann OJ, Walter MA. The establishment of a predictive mutational model of the forkhead domain through the analyses of FOXC2 missense mutations identified in patients with hereditary lymphedema with distichiasis. Hum Mol Genet. 2005 Sep 15;14(18):2619-27. Epub 2005 Aug 4. (http://www.ncbi.nlm.nih.gov/pubmed/16081467?dopt=Abstract)
  • Brice G, Mansour S, Bell R, Collin JR, Child AH, Brady AF, Sarfarazi M, Burnand KG, Jeffery S, Mortimer P, Murday VA. Analysis of the phenotypic abnormalities in lymphoedema-distichiasis syndrome in 74 patients with FOXC2 mutations or linkage to 16q24. J Med Genet. 2002 Jul;39(7):478-83. (http://www.ncbi.nlm.nih.gov/pubmed/12114478?dopt=Abstract)
  • Erickson RP, Dagenais SL, Caulder MS, Downs CA, Herman G, Jones MC, Kerstjens-Frederikse WS, Lidral AC, McDonald M, Nelson CC, Witte M, Glover TW. Clinical heterogeneity in lymphoedema-distichiasis with FOXC2 truncating mutations. J Med Genet. 2001 Nov;38(11):761-6. (http://www.ncbi.nlm.nih.gov/pubmed/11694548?dopt=Abstract)
  • Fang J, Dagenais SL, Erickson RP, Arlt MF, Glynn MW, Gorski JL, Seaver LH, Glover TW. Mutations in FOXC2 (MFH-1), a forkhead family transcription factor, are responsible for the hereditary lymphedema-distichiasis syndrome. Am J Hum Genet. 2000 Dec;67(6):1382-8. Epub 2000 Nov 8. (http://www.ncbi.nlm.nih.gov/pubmed/11078474?dopt=Abstract)
  • OMIM: FORKHEAD BOX C2 (http://omim.org/entry/602402)
  • Mellor RH, Brice G, Stanton AW, French J, Smith A, Jeffery S, Levick JR, Burnand KG, Mortimer PS; Lymphoedema Research Consortium. Mutations in FOXC2 are strongly associated with primary valve failure in veins of the lower limb. Circulation. 2007 Apr 10;115(14):1912-20. Epub 2007 Mar 19. (http://www.ncbi.nlm.nih.gov/pubmed/17372167?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2303)
  • Traboulsi EI, Al-Khayer K, Matsumoto M, Kimak MA, Crowe S, Wilson SE, Finegold DN, Ferrell RE, Meisler DM. Lymphedema-distichiasis syndrome and FOXC2 gene mutation. Am J Ophthalmol. 2002 Oct;134(4):592-6. (http://www.ncbi.nlm.nih.gov/pubmed/12383817?dopt=Abstract)

 

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.

 
Reviewed: February 2008
Published: October 20, 2014