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FOXC2 gene

forkhead box C2
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Normal Function

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).

Health Conditions Related to Genetic Changes

Lymphedema-distichiasis syndrome

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.

More About This Health Condition

Other Names for This Gene

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

Additional Information & Resources

Tests Listed in the Genetic Testing Registry

Scientific Articles on PubMed

Catalog of Genes and Diseases from OMIM

Research Resources

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. Citation on PubMed
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed or Free article on PubMed Central
  • 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. Citation on PubMed
  • 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. Citation on PubMed
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