VEGFC (Vascular Endothelial Growth Factor C): Gene, Function, and Clinical Significance
A comprehensive biomedical overview of the VEGFC gene, its protein product, expression patterns, associated diseases, and molecular functions.
Gene Information Card
| Symbol | VEGFC |
|---|---|
| Full Name | Vascular Endothelial Growth Factor C |
| Gene Type | protein-coding |
| Chromosomal Location | 4q34.3 |
| NCBI Gene ID | 7424 ncbi.nlm.nih.gov/gene/7424 |
| Ensembl ID | ENSG00000150630 |
| UniProt ID | P49767 |
| OMIM ID | 601528 |
| HGNC ID | 12682 |
| Aliases | VEGF-C, Flt4 ligand, VRP |
Description
The VEGFC gene encodes vascular endothelial growth factor C, a member of the VEGF family of growth factors. It is a secreted protein that primarily regulates lymphangiogenesis (the growth of lymphatic vessels) and also plays a role in angiogenesis and endothelial cell survival. VEGFC exerts its effects by binding to and activating the receptor tyrosine kinases VEGFR3 (FLT4) and VEGFR2 (KDR). It is involved in embryonic development, tissue fluid homeostasis, and immune cell trafficking. Dysregulation of VEGFC is associated with various diseases, including cancer (promoting lymphatic metastasis), lymphedema, and inflammatory conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Lymphedema (Milroy-like) | Mutations in VEGFC can impair lymphatic vessel development, leading to lymphatic dysfunction and edema. | OMIM: 601528; ClinVar: pathogenic variants reported |
| Cancer (various types, e.g., breast, colorectal, gastric) | Overexpression of VEGFC promotes lymphangiogenesis and lymphatic metastasis, facilitating tumor spread. | COSMIC: gene expression and copy number alterations; PubMed studies |
| Lymphatic malformations | Aberrant VEGFC signaling contributes to abnormal lymphatic vessel formation. | OMIM: 601528; literature |
| Corneal neovascularization | VEGFC-induced lymphangiogenesis may contribute to pathological corneal blood vessel growth. | PubMed studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 5.2 | Low |
| Lung | 4.8 | Low |
| Kidney | 6.1 | Low |
| Spleen | 3.9 | Low |
| Thymus | 4.5 | Low |
| Small Intestine | 5.0 | Low |
| Colon | 4.7 | Low |
| Muscle | 3.5 | Low |
| Adipose | 4.0 | Low |
| Skin | 5.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HUVEC (umbilical vein endothelial) | 6.0 | Endothelial cells express VEGFC |
| HEK 293 (embryonic kidney) | 5.5 | Common cell line for recombinant expression |
| MCF7 (breast cancer) | 4.2 | Low expression |
| A549 (lung carcinoma) | 5.8 | Moderate expression |
| HeLa (cervical carcinoma) | 4.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.571G>A (p.Ala191Thr) | Missense | Rare (0.01% in gnomAD) | Reported in lymphedema; likely pathogenic |
| c.1042C>T (p.Arg348Ter) | Nonsense | Very rare | Loss-of-function; associated with lymphedema |
| c.574C>T (p.Arg192Cys) | Missense | Rare | Uncertain significance; possibly affects receptor binding |
| Copy number gain | Amplification | Observed in some cancers | Overexpression promotes lymphangiogenesis |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations (e.g., nonsense, frameshift) impair VEGFC's ability to activate VEGFR3, leading to defective lymphatic development and lymphedema.
Gain of Function (GOF)
Gain-of-function mutations or gene amplification lead to overexpression or enhanced activity, promoting excessive lymphangiogenesis, which can facilitate tumor metastasis.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by forming non-functional dimers with wild-type VEGFC, reducing overall signaling.
View complete mutation data：
Gene Ontology (GO)
| • growth factor activity | • vascular endothelial growth factor receptor binding |
| • protein homodimerization activity | • extracellular space |
| • positive regulation of endothelial cell proliferation | • lymphangiogenesis |
| • angiogenesis | • cell differentiation |
| • signal transduction | • response to hypoxia |
Pathways
• VEGF signaling pathway
• Ras signaling pathway
• PI3K-Akt signaling pathway
• Focal adhesion
• Regulation of actin cytoskeleton
• Lymphangiogenesis (KEGG: hsa04370)
Protein Summary
VEGFC is a secreted glycoprotein that undergoes proteolytic processing to generate mature forms with high affinity for VEGFR3 and VEGFR2. It forms homodimers and binds to neuropilin-2 (NRP2) as a co-receptor. The protein is crucial for the development and maintenance of the lymphatic vascular system. It promotes endothelial cell survival, proliferation, and migration. In adults, VEGFC is involved in lymphatic remodeling and immune surveillance. Aberrant expression is linked to tumor lymphangiogenesis and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| VEGFC Knockout HEK293 Cell Line | EDJ-KQ251 | Human | 7424 | Details Get a Quote |
| VEGFC Knockout A-549 Cell Line | EDJ-KQ19449 | Human | 7424 | Details Get a Quote |
| VEGFC Knockout HeLa Cell Line | EDJ-KQ19450 | Human | 7424 | Details Get a Quote |
| VEGFC Knockout HCT 116 Cell Line | EDJ-KQ71696 | Human | 7424 | Details Get a Quote |
| VEGFC Knockout NCI-H1299 Cell Line | EDC90703 | Human | 7424 | Details Get a Quote |
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