FOXC1 Gene: Forkhead Box C1
Key regulator of ocular, cardiovascular, and craniofacial development; associated with Axenfeld-Rieger syndrome and glaucoma
Gene Information Card
| Symbol | FOXC1 |
|---|---|
| Full Name | Forkhead Box C1 |
| Gene Type | Protein coding |
| Chromosomal Location | 6p25.3 |
| NCBI Gene ID | 2296 ncbi.nlm.nih.gov/gene/2296 |
| Ensembl ID | ENSG00000054598 |
| UniProt ID | Q12948 |
| OMIM ID | 601090 |
| HGNC ID | 3800 |
| Aliases | FKHL7, FREAC3, IHG1, IRID1, RIEG3 |
Description
FOXC1 encodes a member of the forkhead family of transcription factors, characterized by a distinct forkhead DNA-binding domain. The protein regulates the expression of genes involved in embryonic development, particularly of the eye, heart, and craniofacial structures. FOXC1 is essential for the formation of the anterior segment of the eye and the development of the cardiac outflow tract. Mutations in FOXC1 cause Axenfeld-Rieger syndrome type 3 and are associated with primary congenital glaucoma and other anterior segment dysgenesis disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Axenfeld-Rieger syndrome type 3 | Haploinsufficiency due to loss-of-function mutations disrupts anterior segment development | OMIM #602482; ClinVar |
| Primary congenital glaucoma | Missense or nonsense mutations impair FOXC1 transcriptional activity, leading to trabecular meshwork dysgenesis | OMIM #231300; ClinVar |
| Anterior segment dysgenesis | Dominant-negative or loss-of-function mutations alter cell migration and differentiation in the developing eye | OMIM #107250; ClinVar |
| Cardiac outflow tract malformations | FOXC1 regulates genes involved in neural crest cell migration; mutations cause conotruncal defects | OMIM #601090; PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Eye (retina, cornea, lens) | 12.5 | High |
| Heart | 8.3 | Medium |
| Brain (cerebellum) | 6.1 | Medium |
| Lung | 4.7 | Low |
| Kidney | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| ARPE-19 (retinal pigment epithelium) | 15.2 | High expression |
| H9 (embryonic stem cells) | 9.8 | Moderate expression |
| HeLa (cervical carcinoma) | 2.1 | Low expression |
| HepG2 (hepatocellular carcinoma) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.255C>A (p.Tyr85*) | Nonsense | Rare | Loss of function; truncation of forkhead domain |
| c.349G>A (p.Gly117Arg) | Missense | Rare | Impaired DNA binding; dominant-negative effect |
| c.402_403insC (p.Leu135Profs*24) | Frameshift | Rare | Loss of function; premature termination |
| c.500T>C (p.Leu167Pro) | Missense | Rare | Reduced transactivation activity |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, and some missense mutations that reduce or abolish DNA binding and transcriptional activation; associated with Axenfeld-Rieger syndrome and glaucoma.
Gain of Function (GOF)
Not commonly reported; most pathogenic FOXC1 mutations are loss-of-function or dominant-negative.
Dominant Negative (DN)
Missense mutations in the forkhead domain (e.g., p.Gly117Arg) that retain dimerization but impair DNA binding, interfering with wild-type FOXC1 function.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Developmental Biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by FOXC1 (Reactome: R-HSA-9616222)
• Anterior segment development (KEGG: hsa04350 – TGF-beta signaling pathway
• indirect)
Protein Summary
FOXC1 is a 553-amino acid transcription factor containing a highly conserved forkhead DNA-binding domain (residues 82–176). It binds to the consensus sequence 5'-RYMAAYA-3' and regulates target genes involved in cell proliferation, migration, and differentiation during embryogenesis. The protein localizes to the nucleus and can act as both an activator and repressor of transcription. Post-translational modifications include phosphorylation, which modulates its activity. FOXC1 is critical for ocular anterior segment formation, and its dysregulation leads to developmental glaucoma and craniofacial anomalies.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXC1 Knockout HEK293 Cell Line | EDJ-KQ3321 | Human | 2296 | Details Get a Quote |
| FOXC1 Knockout A-549 Cell Line | EDJ-KQ24927 | Human | 2296 | Details Get a Quote |
| FOXC1 Knockout HCT 116 Cell Line | EDJ-KQ24928 | Human | 2296 | Details Get a Quote |
| FOXC1 Knockout HeLa Cell Line | EDJ-KQ23544 | Human | 2296 | Details Get a Quote |
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