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FLASH GENE
Symbol FOXC1 contributors: shn/npt/pgu - updated : 24-03-2010
HGNC name forkhead box C1
HGNC id 3800
Corresponding disease
AN aniridia
AXRI Axenfeld-Rieger syndrome, type 3
DEL6PD chromosome 6p subtelomeric deletion syndrome
DWM2 Dandy-Walker malformation-linked locus 2
FOXC1 aniridia and congenital glaucoma
Location 6p25.3      Physical location : 1.610.680 - 1.614.127
Synonym name
  • forkhead-related activator 3
  • transcription factor-like 7
  • myeloid factor-delta
  • forkhead/winged helix-like transcription factor 7
    • Synonym symbol(s) FREAC3, FKHL7, ARA, IGDA, IHG1, IRID1, ARA, RIEG3, FREAC-3
    DNA
    TYPE functioning gene
    STRUCTURE 3.45 kb     1 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D6S1600 - D6S344 - FOXC1- D6S1617 - D6S1713 - cen
    Physical map
    HLA-DRB1 6p21.3 major histocompatibility complex, class II, DR beta 1 C6orf35 6q25.3 chromosome 6 open reading frame 35 LOC389357 6 LOC389357 DUSP22 6p24.3 dual specificity phosphatase 22 IRF4 6p25-p23 interferon regulatory factor 4 SEC5 LOC391990 6 similar to serine palmitoyltransferase, long chain base subunit 2; serine palmitoyltransferase, subunit II HUS1B 6p25.3 HUS1 checkpoint homolog b (S. pombe) LOC340177 6q27 hypothetical LOC340177 LOC389452 6 LOC389452 LOC391991 6 similar to lysR-like transcriptional regulator LOC391992 6 similar to putative heavy metal transporter LOC391993 6 similar to F22G5.20 LOC391994 6 similar to Hypothetical protein FLJ30525 LOC221768 6p25.3 similar to ENSANGP00000010305 FOXQ1 6p25-p23 forkhead box Q1 LOC389358 6 LOC389358 FOXF2 6p25.3 forkhead box F2 LOC221766 6p25.3 hypothetical LOC221766 LOC389359 6 LOC389359 LOC389360 6 LOC389360 LOC389361 6 LOC389361 FOXC1 6p25 forkhead box C1 GMDS 6p25 GDP-mannose 4,6-dehydratase LOC285770 6p25.2 similar to FLJ00254 protein C6orf195 6p25.2 chromosome 6 open reading frame 195 LOC340156 6p25.2 hypothetical protein LOC340156 WRNIP1 6p24.3 Werner helicase interacting protein 1 SERPINB1 6p25 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 1 SERPINB9 6p25 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 9 SERPINB6 6p25 serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 6
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    1 - 3452 57 553 - 2009 19668217
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveliver   lowly
    Hearing/Equilibriumearinnercochlea predominantly
    Urinarykidney   lowly
    Visualeyeanterior segment  highly
     eyeretina  highly
     eyeuveachoroid highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE) highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text fetal tissues, eye
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a forkhead domain with a FH region and a winged helix region which is necessary for normal DNA-binding and transactivation functions
  • two loops-wings on the C-terminal side of helix-turn-helix homeo domain
  • two polymorphic polyglycine tracts
    • mono polymer monomer
    HOMOLOGY
    interspecies homolog to Drosophila homeo forkhead DNA binding domain
    ortholog to Foxc1, Mus musculus
    ortholog to FOXC1, Pan troglodytes
    ortholog to rCG_44068, Rattus norvegicus
    Homologene
    FAMILY
  • forkhead family of transcription factors
    • CATEGORY regulatory , DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • embryonic transcriptional regulator
  • regulation of embryonic ocular (anterior chamber) development
  • important regulator of the chemotactic motility of endothelial cells through the induction of CXCR4 expression
  • playing an an important role in the direct regulation of the FGF19-FGFR4-MAPK pathway to promote both the development and maintenance of anterior segment structures within the eye
  • required for the prepatterning of anterior and posterior domains in the presumptive somites through a putative Notch/Delta/Mesp regulatory loop
  • functions as a tumor suppressor through TGF-beta1mediated signals
  • essential mediator of cellular homeostasis in the eye and indicate that a decreased resistance to oxidative stress may underlie Axenfeld-Rieger-glaucoma pathogenesis
  • playing a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis
  • FOXC1 occupies a conserved element in the MSX2 promoter
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development
    text ocular development
    PATHWAY
    metabolism
    signaling sensory transduction/vision
  • a FOXC1/MSX2 regulatory network functions in the initial stages of osteoblast differentiation
    • a component
    INTERACTION
    DNA binding
    RNA
    small molecule
    protein
  • actin-binding protein filamin A, FLNA
  • pre-B-cell leukemia homeobox 1, PBX1
  • TGFB1 (for negative regulation of cell growth)
  • functional interaction between FOXC1 and PITX2A underlies the sensitivity to FOXC1 gene dosage in Axenfeld-Rieger syndrome and related anterior segment dysgeneses
  • regulates the expression of FOXO1A and binds to a conserved element in the FOXO1A promoter
  • direct target of FGF19 in the eye (FOXC1 positively regulates FGF19 expression in corneal and periocular mesenchymal cells)
  • role in development of the skull and cerebral cortex
  • regulates the expression of FOXO1A and binds to a conserved element in the FOXO1A promoter
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) AXRI , DEL6PD , DWM2 , AN , FOXC1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in endometrial and ovarian cancer
    constitutional   deletion    
    or duplication in eye anterior segment abnormalities, glaucoma
    constitutional somatic mutation      
  • four potentially pathogenic FOXC1 mutations causing amino acid substitutions (P79R, Y115S, G149D, and M161V)
  • responsible for a significant profortion of Axenfeld-Rieger malformation in Germany
    • Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Foxc1 (+/-)mice have anterior segment abnormalities: small or absent Schlemm's canal, aberrantly developed trabecular meshwork, iris hypoplasia, severely eccentric pupils and displaced Schwalbe's line
  • Embryos lacking Foxc1 die pre- or perinatally including defects in the axial skeleton and cardiovascular system
  • compound Foxc1; Foxc2 homozygotes die earlier and with much more severe defects than single homozygotes alone. They have profound abnormalities in the first and second branchial arches, and the early remodeling of blood vessels
  • hypomorphic mouse allele for Foxc1 (Foxc1(hith)) survives into adulthood which embryonic and postnatal histological analyses indicate that diminished Foxc1 protein expression in all three layers of meningeal cells leading to cortical and skull defects, detachment of radial glial endfeet, marginal zone heterotopias and cortical dyslamination
  • Foxc1-null mice have embryonic abnormalities of the rhombic lip due to loss of mesenchyme-secreted signaling molecules with subsequent loss of Atoh1 expression in vermis
  • expression of the Msx2 homeobox gene, an essential regulator of calvarial bone development is absent in the skull mesenchymal progenitors of Foxc1 mutant mice