FOXC2: Forkhead Box C2 Gene
Key regulator in lymphatic and cardiovascular development, associated with lymphedema-distichiasis syndrome
Gene Information Card
| Symbol | FOXC2 |
|---|---|
| Full Name | Forkhead Box C2 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q24.1 |
| NCBI Gene ID | 2303 ncbi.nlm.nih.gov/gene/2303 |
| Ensembl ID | ENSG00000176692 |
| UniProt ID | Q99958 |
| OMIM ID | 602402 |
| HGNC ID | 3817 |
| Aliases | MFH-1, FKHL14, LD, LMPH1B |
Description
FOXC2 encodes a member of the forkhead family of transcription factors, characterized by a conserved DNA-binding forkhead domain. This protein plays a critical role in the development of the lymphatic and cardiovascular systems, as well as in mesodermal cell fate determination. Mutations in FOXC2 are associated with lymphedema-distichiasis syndrome, a condition characterized by lower limb lymphedema and extra rows of eyelashes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lymphedema-distichiasis syndrome | Loss-of-function mutations in FOXC2 disrupt lymphatic valve development, leading to impaired lymph flow and lymphedema, and ectopic eyelash growth due to abnormal eyelid development. | OMIM #153400; ClinVar |
| Lymphedema, hereditary, type 1B | FOXC2 haploinsufficiency causes primary lymphedema with variable penetrance, often presenting at puberty. | OMIM #153400; NCBI Gene |
| Cardiovascular defects | FOXC2 mutations can cause congenital heart defects, including atrial and ventricular septal defects, due to its role in cardiac neural crest cell migration. | OMIM #602402; PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Lymph node | 8.3 | Medium |
| Adipose tissue | 6.7 | Low |
| Lung | 5.2 | Low |
| Kidney | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 15.2 | High expression in endothelial cells |
| Lymphatic endothelial cells | 18.7 | Highest expression, consistent with role in lymphangiogenesis |
| HeLa | 3.4 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.349C>T (p.Arg117*) | Nonsense | Rare | Loss of function; truncates protein, causing lymphedema-distichiasis |
| c.571_572delAG (p.Arg191Glyfs*12) | Frameshift | Rare | Loss of function; premature stop codon, associated with severe lymphedema |
| c.1012G>A (p.Gly338Arg) | Missense | Rare | Likely loss of function; disrupts forkhead domain DNA binding |
Mutation functional classification
Loss of Function (LOF)
Most FOXC2 mutations are loss-of-function, leading to haploinsufficiency and lymphedema-distichiasis syndrome.
Gain of Function (GOF)
No gain-of-function mutations reported in FOXC2.
Dominant Negative (DN)
Some missense mutations may act as dominant-negative by interfering with wild-type FOXC2 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Lymphatic vessel development (Reactome: R-HSA-9013405)
• VEGF signaling pathway (KEGG: hsa04370)
• Cardiac neural crest cell development (GO:0010002)
Protein Summary
FOXC2 is a 501-amino acid transcription factor with a conserved forkhead DNA-binding domain. It regulates genes involved in lymphatic valve formation, endothelial cell migration, and cardiovascular morphogenesis. The protein is predominantly nuclear and interacts with other transcription factors to modulate gene expression during embryonic development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| FOXC2 Knockout HEK293 Cell Line | EDJ-KQ4607 | Human | 2303 | Details Get a Quote |
| FOXC2 Knockout HeLa Cell Line | EDJ-KQ27277 | Human | 2303 | Details Get a Quote |
| FOXC2 Knockout A-549 Cell Line | EDJ-KQ61727 | Human | 2303 | Details Get a Quote |
| FOXC2 Knockout HCT 116 Cell Line | EDJ-KQ70212 | Human | 2303 | Details Get a Quote |
