Skip Navigation
Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

FOXC1

Reviewed January 2014

What is the official name of the FOXC1 gene?

The official name of this gene is “forkhead box C1.”

FOXC1 is the gene's official symbol. The FOXC1 gene is also known by other names, listed below.

What is the normal function of the FOXC1 gene?

The FOXC1 gene provides instructions for making a protein that attaches (binds) to specific regions of DNA and regulates the activity of other genes. On the basis of this action, the FOXC1 protein is called a transcription factor.

The FOXC1 protein plays a critical role in early development, particularly in the formation of structures in the front part of the eye (the anterior segment). These structures include the colored part of the eye (the iris), the lens of the eye, and the clear front covering of the eye (the cornea). Studies suggest that the FOXC1 protein may also have functions in the adult eye, such as helping cells respond to oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that can damage or kill cells.

The FOXC1 protein is also involved in the normal development of other parts of the body, including the heart, kidneys, and brain.

Does the FOXC1 gene share characteristics with other genes?

The FOXC1 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 FOXC1 gene related to health conditions?

Axenfeld-Rieger syndrome - caused by mutations in the FOXC1 gene

More than 50 mutations in the FOXC1 gene have been found to cause Axenfeld-Rieger syndrome type 3, a condition that primarily affects the development of the anterior segment of the eye but can also affect other parts of the body. Many FOXC1 gene mutations reduce the amount of functional FOXC1 protein that is produced or result in a defective protein that cannot regulate the activity of other genes. Other genetic changes (such as a duplication of the FOXC1 gene) likely increase the amount or function of the FOXC1 protein. Having either too little or too much activity of this protein disrupts the regulation of other genes needed for normal development.

Changes in the amount or function of the FOXC1 protein impairs the development of the anterior segment of the eye, leading to the eye abnormalities characteristic of Axenfeld-Rieger syndrome. In some cases, changes involving the FOXC1 protein also cause problems with development of other parts of the body.

Peters anomaly - caused by mutations in the FOXC1 gene

At least two mutations in the FOXC1 gene have been found to cause Peters anomaly. This condition is characterized by abnormal development of the anterior segment and clouding of the cornea. The mutations that cause Peters anomaly likely disrupt the protein's ability to regulate the expression of developmental genes, especially affecting the eye. Abnormal formation of the iris, cornea, and other structures of the anterior segment leads to the features of Peters anomaly. The FOXC1 gene mutations that cause Peters anomaly can cause other related eye disorders, such as Axenfeld-Rieger syndrome (described above), in members of the same family.

other disorders - caused by mutations in the FOXC1 gene

Mutations in the FOXC1 gene have also been identified in another eye disorder called iridogoniodysgenesis type 1. Like Axenfeld-Rieger syndrome and Peters anomaly, this condition primarily involves the anterior segment of the eye. Iridogoniodysgenesis type 1 is associated with underdevelopment of the iris and an elevated risk of increased pressure in the eye (glaucoma).

FOXC1 gene mutations have been reported in a few people with abnormalities of brain development. Mutations that change single protein building blocks (amino acids) in the FOXC1 protein have been associated with defects of the cerebellum, which is the part of the brain that is involved in coordinating movement. Additionally, deletions of genetic material from a region of chromosome 6 that includes the FOXC1 gene and several neighboring genes have been associated with a structural abnormality of the cerebellum known as Dandy-Walker syndrome.

Where is the FOXC1 gene located?

Cytogenetic Location: 6p25

Molecular Location on chromosome 6: base pairs 1,610,445 to 1,613,896

The FOXC1 gene is located on the short (p) arm of chromosome 6 at position 25.

The FOXC1 gene is located on the short (p) arm of chromosome 6 at position 25.

More precisely, the FOXC1 gene is located from base pair 1,610,445 to base pair 1,613,896 on chromosome 6.

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 FOXC1?

You and your healthcare professional may find the following resources about FOXC1 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 FOXC1 gene or gene products?

  • FKHL7
  • forkhead box protein C1
  • forkhead, drosophila, homolog-like 7
  • forkhead-related activator 3
  • forkhead-related protein FKHL7
  • forkhead-related transcription factor 3
  • forkhead/winged helix-like transcription factor 7
  • FOXC1_HUMAN
  • FREAC3
  • FREAC-3
  • myeloid factor-delta

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 FOXC1?

acids ; anterior ; cerebellum ; chromosome ; cornea ; DNA ; duplication ; free radicals ; gene ; glaucoma ; myeloid ; oxidative stress ; protein ; stress ; 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

  • Aldinger KA, Lehmann OJ, Hudgins L, Chizhikov VV, Bassuk AG, Ades LC, Krantz ID, Dobyns WB, Millen KJ. FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation. Nat Genet. 2009 Sep;41(9):1037-42. doi: 10.1038/ng.422. Epub 2009 Aug 9. (http://www.ncbi.nlm.nih.gov/pubmed/19668217?dopt=Abstract)
  • Berry FB, Lines MA, Oas JM, Footz T, Underhill DA, Gage PJ, Walter MA. Functional interactions between FOXC1 and PITX2 underlie the sensitivity to FOXC1 gene dose in Axenfeld-Rieger syndrome and anterior segment dysgenesis. Hum Mol Genet. 2006 Mar 15;15(6):905-19. Epub 2006 Jan 31. (http://www.ncbi.nlm.nih.gov/pubmed/16449236?dopt=Abstract)
  • D'haene B, Meire F, Claerhout I, Kroes HY, Plomp A, Arens YH, de Ravel T, Casteels I, De Jaegere S, Hooghe S, Wuyts W, van den Ende J, Roulez F, Veenstra-Knol HE, Oldenburg RA, Giltay J, Verheij JB, de Faber JT, Menten B, De Paepe A, Kestelyn P, Leroy BP, De Baere E. Expanding the spectrum of FOXC1 and PITX2 mutations and copy number changes in patients with anterior segment malformations. Invest Ophthalmol Vis Sci. 2011 Jan 21;52(1):324-33. doi: 10.1167/iovs.10-5309. (http://www.ncbi.nlm.nih.gov/pubmed/20881294?dopt=Abstract)
  • Honkanen RA, Nishimura DY, Swiderski RE, Bennett SR, Hong S, Kwon YH, Stone EM, Sheffield VC, Alward WL. A family with Axenfeld-Rieger syndrome and Peters Anomaly caused by a point mutation (Phe112Ser) in the FOXC1 gene. Am J Ophthalmol. 2003 Mar;135(3):368-75. (http://www.ncbi.nlm.nih.gov/pubmed/12614756?dopt=Abstract)
  • Lehmann OJ, Ebenezer ND, Ekong R, Ocaka L, Mungall AJ, Fraser S, McGill JI, Hitchings RA, Khaw PT, Sowden JC, Povey S, Walter MA, Bhattacharya SS, Jordan T. Ocular developmental abnormalities and glaucoma associated with interstitial 6p25 duplications and deletions. Invest Ophthalmol Vis Sci. 2002 Jun;43(6):1843-9. (http://www.ncbi.nlm.nih.gov/pubmed/12036988?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2296)
  • Nishimura DY, Searby CC, Alward WL, Walton D, Craig JE, Mackey DA, Kawase K, Kanis AB, Patil SR, Stone EM, Sheffield VC. A spectrum of FOXC1 mutations suggests gene dosage as a mechanism for developmental defects of the anterior chamber of the eye. Am J Hum Genet. 2001 Feb;68(2):364-72. Epub 2001 Jan 18. (http://www.ncbi.nlm.nih.gov/pubmed/11170889?dopt=Abstract)
  • Reis LM, Tyler RC, Volkmann Kloss BA, Schilter KF, Levin AV, Lowry RB, Zwijnenburg PJ, Stroh E, Broeckel U, Murray JC, Semina EV. PITX2 and FOXC1 spectrum of mutations in ocular syndromes. Eur J Hum Genet. 2012 Dec;20(12):1224-33. doi: 10.1038/ejhg.2012.80. Epub 2012 May 9. (http://www.ncbi.nlm.nih.gov/pubmed/22569110?dopt=Abstract)
  • Strungaru MH, Dinu I, Walter MA. Genotype-phenotype correlations in Axenfeld-Rieger malformation and glaucoma patients with FOXC1 and PITX2 mutations. Invest Ophthalmol Vis Sci. 2007 Jan;48(1):228-37. (http://www.ncbi.nlm.nih.gov/pubmed/17197537?dopt=Abstract)
  • Tümer Z, Bach-Holm D. Axenfeld-Rieger syndrome and spectrum of PITX2 and FOXC1 mutations. Eur J Hum Genet. 2009 Dec;17(12):1527-39. doi: 10.1038/ejhg.2009.93. Epub 2009 Jun 10. Review. (http://www.ncbi.nlm.nih.gov/pubmed/19513095?dopt=Abstract)
  • Weisschuh N, Wolf C, Wissinger B, Gramer E. A novel mutation in the FOXC1 gene in a family with Axenfeld-Rieger syndrome and Peters' anomaly. Clin Genet. 2008 Nov;74(5):476-80. doi: 10.1111/j.1399-0004.2008.01025.x. Epub 2008 May 21. (http://www.ncbi.nlm.nih.gov/pubmed/18498376?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: January 2014
Published: November 24, 2014