Forkhead box protein C2 (FOXC2) also known asforkhead-related protein FKHL14 (FKHL14),transcription factor FKH-14, ormesenchyme fork head protein 1 (MFH1) is aprotein that in humans is encoded by theFOXC2gene.[5][6] FOXC2 is a member of thefork head box (FOX) family oftranscription factors.
The protein is 501 amino acids in length. The gene has nointrons; the singleexon is approximately 1.5kb in size.[6][7]
FOX transcription factors are expressed during development and are associated with a number of cellular and developmentaldifferentiation processes. FOXC2 is required during early development of the kidneys, including differentiation ofpodocytes and maturation of theglomerular basement membrane. It is also involved in the early development of the heart.[8]
An increased expression of FOXC2 in adipocytes can increase the amount of brown adipose tissue leading to lower weight and an increased sensitivity to insulin.[9][10]
Absence of FOXC2 has been shown to lead to the failure of lymphatic valves to form and problems with lymphatic remodelling. A number of mutations in the FOXC2 gene have been associated withLymphedema–distichiasis syndrome,[11][12] It has also been suggested that there may be a link between polymorphisms in FOXC2 and varicose veins.[12][13]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Kaestner KH, Bleckmann SC, Monaghan AP, Schlöndorff J, Mincheva A, Lichter P, Schütz G (June 1996). "Clustered arrangement of winged helix genes fkh-6 and MFH-1: possible implications for mesoderm development".Development.122 (6):1751–8.doi:10.1242/dev.122.6.1751.PMID8674414.
^abMiura N, Iida K, Kakinuma H, Yang XL, Sugiyama T (May 1997). "Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures".Genomics.41 (3):489–92.doi:10.1006/geno.1997.4695.PMID9169153.
Fauret AL, Tuleja E, Jeunemaitre X, Vignes S (2010). "A novel missense mutation and two microrearrangements in the FOXC2 gene of three families with lymphedema-distichiasis syndrome".Lymphology.43 (1):14–8.PMID20552815.
Witte MH, Erickson RP, Khalil M, et al. (2009). "Lymphedema-distichiasis syndrome without FOXC2 mutation: evidence for chromosome 16 duplication upstream of FOXC2".Lymphology.42 (4):152–60.PMID20218083.
Vreeburg M, Heitink MV, Damstra RJ, et al. (2008). "Lymphedema-distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene".Int. J. Dermatol.47 (Suppl 1):52–5.doi:10.1111/j.1365-4632.2008.03962.x.PMID18986489.S2CID10265549.
Ma GC, Liu CS, Chang SP, et al. (2008). "A recurrent ITGA9 missense mutation in human fetuses with severe chylothorax: possible correlation with poor response to fetal therapy".Prenat. Diagn.28 (11):1057–63.doi:10.1002/pd.2130.PMID18973153.S2CID206346009.
Pappa KI, Gazouli M, Economou K, et al. (2010). "Gestational diabetes mellitus shares polymorphisms of genes associated with insulin resistance and type 2 diabetes in the Greek population".Gynecological Endocrinology.27 (4):267–272.doi:10.3109/09513590.2010.490609.PMID20540670.S2CID28980963.
Ghalamkarpour A, Debauche C, Haan E, et al. (2009). "Sporadic in utero generalized edema caused by mutations in the lymphangiogenic genes VEGFR3 and FOXC2".J. Pediatr.155 (1):90–3.doi:10.1016/j.jpeds.2009.02.023.PMID19394045.
Horra A, Salazar J, Ferré R, et al. (2009). "Prox-1 and FOXC2 gene expression in adipose tissue: A potential contributory role of the lymphatic system to familial combined hyperlipidaemia".Atherosclerosis.206 (2):343–5.doi:10.1016/j.atherosclerosis.2009.02.026.PMID19339011.
