| 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 and FOXC2 are forkhead transcription factors that play essential roles during development and physiology |
|
FOXC1 occupies a conserved element in the MSX2 promoter |
|
sets potentially a threshold for the BMP-dependent activation of MSX2, thus controlling the differentiation of osteogenic precursor cells and the rate and pattern of calvarial bone development |
|
is a specific transcriptional regulator essential for development and maintenance of the mesenchymal niches for haematopoietic stem and progenitor cells |
|
essential role for FOXC1 in the early stage of vascular formation in the telencephalon |
|
FOXC1, GMDS, FOXF2, and FOXQ1 may represent loci for enhancer-driven changes in gene expression that could affect the developing embryo |
|
encodes a developmental transcription factor required for brain, heart, and eye development |
CELLULAR PROCESS
 |
nucleotide, transcription, regulation
|
| PHYSIOLOGICAL PROCESS
|
development
|
| signaling
|
sensory transduction/vision
|
|
| a FOXC1/MSX2 regulatory network functions in the initial stages of osteoblast differentiation |
|
FOXC1 - FGF8 signaling regulates mammalian jaw patterning, providing a mechanistic basis for the pathogenesis of syngnathia |
| 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 |
|
MMP7 is a key downstream effector of FOXC1-mediated invasiveness in breast cancer |
|
FOXC1 regulates the expression of RAB3GAP1, RAB3GAP2 and SNAP25, three genes with central roles in both exocytosis and endocytosis, responsible for extracellular trafficking |
|
FOXC1 promotes colorectal cancer metastasis through transactivating ITGA7 and FGFR4 expression |
| Other morbid association(s)
|
| Type | Gene Modification | Chromosome rearrangement | Protein expression | Protein 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 | | constitutional
| germinal mutation
|
|
|
| |
associated white matter hyperintensities, dilated perivascular spaces, and lacunar infarction, by patients with cerebral small-vessel disease (CSVD) | | tumoral
|
|
| --over
|
| |
is associated with poor prognosis in pancreatic ductal adenocarcinoma | | constitutional
|
|
|
| loss of function
| |
altered FOXC1 function associated to cerebral small-vessel disease (CSVD) | |
Variant & Polymorphism
| 
| |
Candidate gene
Marker
Therapy target
|
|
| System | Type | Disorder | Pubmed |
|---|
| cancer | endocrine | pancreas | |
| may provide an opportunity for developing a novel therapeutic target as well as a prognostic marker in PDA (pancreatic ductal adenocarcinoma) |
| | | |
|
| 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 |
|
mice carrying the null-mutated Foxc1 gene frequently develop an anomalous double collecting system |
|
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 |
