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Symbol FOXC2 contributors: mct/npt - updated : 28-06-2014
HGNC name forkhead box C2 (MFH-1, mesenchyme forkhead 1)
HGNC id 3801
Corresponding disease
LPDD lymphedema-distichiasis syndrome
YNS yellow nail syndrome
Location 16q24.1      Physical location : 86.600.856 - 86.602.535
Synonym name
  • mesenchyme forkhead 1
  • forkhead,Drosophila homolog like 14
  • mesenchyme fork head protein 1
  • Synonym symbol(s) MFH1, FKHL14, LPDD, FXC2, EVI96, LD, MFH-1
    TYPE functioning gene
    SPECIAL FEATURE arranged in tandem, component of a cluster
    text arranged in tandem with FOXL1, FOXF1
    STRUCTURE 1.51 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    text structure intronless
    MAPPING cloned Y linked N status confirmed
    Map cen - FOXF1 - FOXC2 - FOXL1 - X - D16S496 - qter
    Authors Fang (00)
    Text X breakpoint in the t(Y;16 ); q12-q24.3 translocation
    Physical map
    KIAA1609 16q24.1 KIAA1609 protein COTL1 16q24.1 coactosin-like 1 (Dictyostelium) C16orf44 16q24.1 chromosome 16 open reading frame 44 USP10 16q24.1 ubiquitin specific protease 10 DKFZP434B044 16q24.1 hypothetical protein DKFZp434B044 LOC123862 16q24.1 similar to Interferon-induced transmembrane protein 3 (Interferon-inducible protein 1-8U) ZDHHC7 16q23.3 zinc finger, DHHC domain containing 7 KIAA0513 16q24.1 KIAA0513 gene product FLJ44299 16q24.1 FLJ44299 protein LOC123855 16q24.1 similar to ENSANGP00000013733 MGC22001 16q24.1 hypothetical protein MGC22001 LOC388303 16 LOC388303 LOC388304 16 LOC388304 KIAA0182 16q24 LOC388304 Pfs2 16q24.1 DNA replication complex GINS protein PSF2 NOC4 16q24.3 neighbor of COX4 COX4I1 16q24.2 cytochrome c oxidase subunit IV isoform 1 LOC390744 16 similar to ribosomal protein L10a ICSBP1 16q24.1 interferon consensus sequence binding protein 1 LOC390745 16 similar to hypothetical protein Tb927.2.5760 LOC390746 16 similar to Chloride intracellular channel protein 1 (Nuclear chloride ion channel 27) (NCC27) (p64 CLCP) (Chloride channel ABP) FOXF1 16q24 forkhead box F1 FLJ12998 16q24.1 hypothetical protein FLJ12998 FLJ30679 16q24.1 hypothetical protein FLJ30679 FOXC2 16q24.3 forkhead box C2 (MFH-1, mesenchyme forkhead 1) FOXL1 16q24.3 forkhead box L1 LOC388305 16 LOC388305 MGC15419 16q24.2 MGC15419 protein MAP1LC3B 16q24.1 microtubule-associated protein 1 light chain 3 beta BDG29 16q24.2 BDG-29 proten JPH3 16q24.3 junctophilin 3 DKFZp434G0522 16q24.3 hypothetical protein DKFZp434G0522 SLC7A5 16q24.3 solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 CA5A 16q24.3 carbonic anhydrase VA, mitochondrial BANP 16q24 carbonic anhydrase VA, mitochondrial LOC388306 16 LOC388306 LOC390747 16 similar to proline rich protein ZNF469 16q24 zinc finger protein 469 ZFPM1 16q24.3 zinc finger protein, multitype 1
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 1683 - 501 - 2006 1645610
    Type restricted
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Nervousnervecranial nerve   
    Reproductivefemale systemuterus   
    Respiratorylung   moderately
    Urinarykidneynephronrenal capsuleglomerulus 
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    cell lineage
    cell lines
    at STAGE
    physiological period embryo
    Text embryonic mesoderm
    anterior rhombomeres, in the developing lymphatic vessels
  • a forkhead with (FH, winged helix) domain and DNA-binding motif
  • two loops-wings on the C-terminal side of an helix-turn-helix homeo domain
    interspecies homolog to murine mesenchyme forkhead 1 (MFH-1)
    homolog to Drosophila homeo forkhead
    homolog to murine Foxc2
  • HNF-3 FKH family of transcriptional activators
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • embryonic transcriptional regulator, playing a role in adipocyte metabolism by increasing the sensitivity of the beta-adremergic CAMP protein kinase A
  • involved in the specification of the lymphatic capillary versus collecting lymphatic vessel
  • playing a central role in promoting invasion and metastasis and that it may prove to be a highly specific molecular marker for human basal-like breast cancers
  • common transcriptional activator of insulin and TGF-beta signaling to directly regulate SERPINE1 expression via 2 distinct target sites, an insulin response element (IRE) and a novel forkhead-binding element (FBE), adjacent to a SMAD-binding site
  • controls the expression of a distinct set of podocyte genes involved in podocyte differentiation and glomerular basement membrane maturation
  • important regulator of the chemotactic motility of endothelial cells through the induction of CXCR4 expression
  • playing an important role for the normal development and maintenance of venous and lymphatic valves (Mellor 2007)
  • plays a role in conditions such as obesity, dyslipidemia, and type 2 diabetes
  • essential regulator of the cardiovascular system in development and disease
  • regulates angiogenesis via multiple signaling pathways, including ITGB3, CXCR4, and DLL4
  • implicated in cancer progression through its induction of epithelial-to-mesenchymal transition
  • important metabo-regulator of mitochondrial morphology and metabolism
  • plays an important role in regulation of metabolism, arterial specification, and vascular sprouting
  • plays an important role in osteoblastogenesis by promoting osteoblast proliferation, survival and differentiation through up-regulation of ITGB1 in response to stimuli which induce bone formation
  • FOXC1 and FOXC2 are forkhead transcription factors that play essential roles during development and physiology
  • new role in regulating proliferation and preventing premature differentiation of activated muscle satellite cells
  • forkhead transcription factor that plays an essential role in lymphatic vascular development
  • pivotal role of phosphorylation in the regulation of FOXC2-mediated transcription in lymphatic endothelial cells and importance of FOXC2 phosphorylation in vascular development
  • required for the maintenance of the mesenchymal phenotype after TGFB1 induced EMT in human ovarian cancer cells
  • CELLULAR PROCESS nucleotide, transcription
    metabolism lipid/lipoprotein
    signaling sensory transduction/vision
    mesenchymal development
    a component
    DNA binding
    small molecule
  • interacting with ANGPT2 (controls ANGPT2 expression by direct activation of its promoter in adipocytes, promoter that alters vascular patterning, remodeling, maturation, and functions)
  • key molecule to regulate SERPINE1 gene expression
  • interacting with ITGB3 (directly induces ITGB3 expression and regulates angiogenesis by ITGB3-mediated endothelial cell adhesion and migration)
  • induces WNT signaling by direct interaction with the WNT4 (wingless-type MMTV integration site family member-4) promoter region
  • enhanced the expression of CTNNB1, an important modulator of osteoblastogenesis
  • requirement of FOXC2 for inorganic phosphate (Pi)-induced osteopontin (SPP1) expression and secretion from cancer cells as necessary for the angiogenic response
  • cell & other
    induced by high fat diet and counteracting most of the symptoms associated with obesity,hypertriglyceridemia and diet-induced insulin resistance
    during the course of tumor progression and that it might play a causal role in enabling metastatic dissemination
    corresponding disease(s) LPDD , YNS
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in metastatic cancer cells
    tumoral     --over  
    in invasive ovarian cancer cell lines and tissues
    constitutional     --over  
    in bone marrow mesenchymal stem cells (BMSCs), may promote osteogenic differentiation and inhibit adipogenic differentiation, and this effect can be mediated via activating the canonical Wnt-CTNNB1signaling pathway (PMId: 24122419)
    tumoral     --over  
    in esophageal squamous cell carcinoma with advanced tumor stage, lymph node metastasis, and lymphatic invasion
    Susceptibility to varicose veins and hemorrhoids
    Variant & Polymorphism other mutations strongly associated with primary venous valve failure in both the superficial and deep veins in the lower limb (Mellor 2007)
    Candidate gene
    Therapy target functional interference with FOXC2 or ANGPT2 might provide a therapeutic approach for prevention and treatment of obesity or its related disorders
    FOXC2 knockout mouse displaying anterior segment abnormalities,craniofacial,cardiovascular and vertebrate anomalies