FOXC2

Forkhead box C2 (MFH-1, mesenchyme forkhead 1)
PDB rendering based on 1d5v.
Available structures PDB 1d5v
Identifiers
Symbols	FOXC2; FKHL14; LD; MFH-1; MFH1
External IDs	OMIM: 602402 MGI: 1347481 HomoloGene: 21091 GeneCards: FOXC2 Gene
Gene Ontology Molecular function • double-stranded DNA binding • sequence-specific DNA binding transcription factor activity • sequence-specific enhancer binding RNA polymerase II transcription factor activity • transcription factor binding • DNA bending activity • chromatin DNA binding • sequence-specific DNA binding • transcription regulatory region DNA binding Cellular component • nucleus • transcription factor complex Biological process • negative regulation of transcription from RNA polymerase II promoter • skeletal system development • ossification • blood vessel development • patterning of blood vessels • vasculogenesis • metanephros development • ureteric bud development • somitogenesis • lymphangiogenesis • blood vessel remodeling • heart morphogenesis • transcription, DNA-dependent • anti-apoptosis • Notch signaling pathway • multicellular organismal development • mesoderm development • heart development • cell proliferation • insulin receptor signaling pathway • response to hormone stimulus • positive regulation of endothelial cell migration • neural crest cell development • neural crest cell fate commitment • collagen fibril organization • positive regulation of cell adhesion mediated by integrin • embryonic heart tube development • positive regulation of vascular wound healing • camera-type eye development • positive regulation of transcription, DNA-dependent • positive regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter • regulation of organ growth • vascular endothelial growth factor receptor signaling pathway • paraxial mesoderm formation • paraxial mesodermal cell fate commitment • embryonic viscerocranium morphogenesis • artery morphogenesis • regulation of blood vessel size • regulation of sequence-specific DNA binding transcription factor activity • ventricular cardiac muscle tissue morphogenesis • cardiac muscle cell proliferation • glomerular endothelium development • glomerular visceral epithelial cell differentiation • glomerular mesangial cell development • positive regulation of cell migration involved in sprouting angiogenesis Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	2303	14234
Ensembl	ENSG00000176692	ENSMUSG00000046714
UniProt	Q99958	Q61850
RefSeq (mRNA)	NM_005251	NM_013519.2
RefSeq (protein)	NP_005242	NP_038547.2
Location (UCSC)	Chr 16: 86.6 – 86.6 Mb	Chr 8: 123.64 – 123.64 Mb
PubMed search	[1]	[2]

Forkhead box protein C2 (FOXC2) also known as forkhead-related protein FKHL14 (FKHL14), transcription factor FKH-14, or mesenchyme fork head protein 1 (MFH1) is a protein that in humans is encoded by the FOXC2 gene. FOXC2 is a member of the fork head box (FOX) family of transcription factors.

Clinical significance

Mutations in the FOXC2 gene are associated with lymphedema distichiasis, and that has been studied to determine if it is associated with varicose veins.

FOXC2 is also involved in cancer metastases. In particular, expression of FOXC2 is induced when epithelial cells undergo an epithelial-mesenchymal transition (EMT) and become mesenchymal looking cells. EMT can be induced by a number of genes including Snail, Twist, Goosecoid, and TGF-beta 1. Suppression of FOXC2 expression using shRNA in a highly metastatic breast cancer model blocks their metastatic ability.

Further reading

• 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. PMID 20552815. 
• 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. PMID 20218083. 
• de Mooij YM, van den Akker NM, Bekker MN, et al. (2009). "Abnormal Shh and FOXC2 expression correlates with aberrant lymphatic development in human fetuses with increased nuchal translucency.". Prenat. Diagn. 29 (9): 840–6. doi:10.1002/pd.2316. PMID 19548265. 
• Sano H, Leboeuf JP, Novitskiy SV, et al. (2010). "The Foxc2 transcription factor regulates tumor angiogenesis.". Biochem. Biophys. Res. Commun. 392 (2): 201–6. doi:10.1016/j.bbrc.2010.01.015. PMC 2822046. PMID 20060810. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2822046. 
• 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. PMID 18986489. 
• Kume T (2008). "Foxc2 transcription factor: a newly described regulator of angiogenesis.". Trends Cardiovasc. Med. 18 (6): 224–8. doi:10.1016/j.tcm.2008.11.003. PMC 2674371. PMID 19185813. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2674371. 
• Yoshida T, Kato K, Fujimaki T, et al. (2009). "Association of a polymorphism of the apolipoprotein E gene with chronic kidney disease in Japanese individuals with metabolic syndrome.". Genomics 93 (3): 221–6. doi:10.1016/j.ygeno.2008.11.001. PMID 19056482. 
• 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. PMID 18973153. 
• Yerges LM, Klei L, Cauley JA, et al. (2009). "High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.". J. Bone Miner. Res. 24 (12): 2039–49. doi:10.1359/jbmr.090524. PMC 2791518. PMID 19453261. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2791518. 
• Lu Y, Dollé ME, Imholz S, et al. (2008). "Multiple genetic variants along candidate pathways influence plasma high-density lipoprotein cholesterol concentrations.". J. Lipid Res. 49 (12): 2582–9. doi:10.1194/jlr.M800232-JLR200. PMID 18660489. 
• van Steensel MA, Damstra RJ, Heitink MV, et al. (2009). "Novel missense mutations in the FOXC2 gene alter transcriptional activity.". Hum. Mutat. 30 (12): E1002–9. doi:10.1002/humu.21127. PMID 19760751. 
• 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 : the official journal of the International Society of Gynecological Endocrinology 27 (4): HASH(0x28c7db0). doi:10.3109/09513590.2010.490609. PMID 20540670. 
• Joslyn G, Ravindranathan A, Brush G, et al. (2010). "Human variation in alcohol response is influenced by variation in neuronal signaling genes". Alcohol. Clin. Exp. Res. 34 (5): 800–12. doi:10.1111/j.1530-0277.2010.01152.x. PMID 20201926. 
• Fabretto A, Shardlow A, Faletra F, et al. (2010). "A case of lymphedema-distichiasis syndrome carrying a new de novo frameshift FOXC2 mutation". Ophthalmic Genet. 31 (2): 98–100. doi:10.3109/13816811003620517. PMID 20450314. 
• 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. PMID 19394045. 
• Silander K, Alanne M, Kristiansson K, et al. (2008). Janssens, A. Cecile J.W.. ed. "Gender differences in genetic risk profiles for cardiovascular disease". PLoS ONE 3 (10): e3615. doi:10.1371/journal.pone.0003615. PMC 2574036. PMID 18974842. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2574036. 
• Dellinger MT, Thome K, Bernas MJ, et al. (2008). "Novel FOXC2 missense mutation identified in patient with lymphedema-distichiasis syndrome and review". Lymphology 41 (3): 98–102. PMID 19013876. 
• Corpeleijn E, Petersen L, Holst C, et al. (2010). "Obesity-related polymorphisms and their associations with the ability to regulate fat oxidation in obese Europeans: the NUGENOB study". Obesity (Silver Spring) 18 (7): 1369–77. doi:10.1038/oby.2009.377. PMID 19876004. 
• 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. PMID 19339011. 
• Hader C, Marlier A, Cantley L (2010). "Mesenchymal-epithelial transition in epithelial response to injury: the role of Foxc2". Oncogene 29 (7): 1031–40. doi:10.1038/onc.2009.397. PMC 2824778. PMID 19935708. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2824778. 

External links

• GeneReviews/NCBI/NIH/UW entry on Lymphedema-Distichiasis Syndrome