GC (GC Vitamin D Binding Protein)
Vitamin D Binding Protein (GC) – Gene, Function, and Clinical Significance
Gene Information Card
| Symbol | GC |
|---|---|
| Full Name | GC, vitamin D binding protein |
| Gene Type | protein-coding |
| Chromosomal Location | 4q13.3 |
| NCBI Gene ID | 2638 ncbi.nlm.nih.gov/gene/2638 |
| Ensembl ID | ENSG00000145321 |
| UniProt ID | P02774 |
| OMIM ID | 139200 |
| HGNC ID | 4187 |
| Aliases | DBP, VDBP, group-specific component, Gc-globulin |
Description
The GC gene encodes vitamin D binding protein (DBP), also known as group-specific component (Gc-globulin). DBP is a multifunctional serum protein primarily responsible for binding and transporting vitamin D and its metabolites, including 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. It also plays roles in actin scavenging, macrophage activation, and fatty acid transport. Polymorphisms in GC are associated with variations in vitamin D levels and susceptibility to certain diseases.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| GC deficiency (vitamin D binding protein deficiency) | Loss-of-function mutations in GC lead to reduced DBP levels, impairing vitamin D transport and causing low serum 25-hydroxyvitamin D levels, potentially contributing to rickets or osteomalacia. | OMIM #139200, case reports |
| Chronic obstructive pulmonary disease (COPD) | GC polymorphisms (e.g., rs7041, rs4588) are associated with altered DBP levels and COPD susceptibility, possibly through effects on vitamin D status and inflammation. | GWAS, meta-analyses |
| Type 2 diabetes | GC variants influence vitamin D bioavailability and have been linked to insulin resistance and type 2 diabetes risk in some populations. | Candidate gene studies, meta-analyses |
| Tuberculosis | Low DBP levels and specific GC genotypes are associated with increased susceptibility to tuberculosis, likely due to impaired macrophage activation. | Case-control studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | ~500 | High |
| Kidney | ~10 | Low |
| Adipose tissue | ~5 | Low |
| Lung | ~3 | Low |
| Placenta | ~2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (hepatocellular carcinoma) | ~400 | High expression; major source of DBP |
| Huh-7 (hepatoma) | ~350 | High expression |
| A549 (lung carcinoma) | ~2 | Low expression |
| HEK293 (embryonic kidney) | ~1 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1307C>A (p.Thr436Lys) | SNP (rs7041) | ~40% (global) | Alters DBP affinity for vitamin D metabolites; associated with lower 25(OH)D levels |
| c.1296T>G (p.Asp432Glu) | SNP (rs4588) | ~25% (global) | Reduces DBP levels; linked to vitamin D insufficiency |
| c.1A>G (p.Met1Val) | Missense | Rare | Likely loss-of-function; reported in GC deficiency |
| c.658G>A (p.Gly220Arg) | Missense | Rare | Reported in GC deficiency; impairs actin binding |
Mutation functional classification
Loss of Function (LOF)
Nonsense, frameshift, or missense mutations that severely reduce DBP protein levels or disrupt vitamin D binding (e.g., p.Met1Val, p.Gly220Arg) lead to GC deficiency and impaired vitamin D transport.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for GC.
Dominant Negative (DN)
No dominant-negative effects described; GC deficiency is typically autosomal recessive.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Vitamin D metabolism and transport (Reactome: R-HSA-196791)
• Scavenging of heme from plasma (Reactome: R-HSA-2168880)
• Actin dynamics (Reactome: R-HSA-5663222)
Protein Summary
Vitamin D binding protein (DBP) is a 58 kDa glycoprotein synthesized primarily in the liver. It circulates in plasma at high concentrations (~300-600 mg/L) and binds >85% of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. DBP also binds monomeric actin, preventing polymerization and clearing actin from the circulation after cell injury. Additionally, DBP is converted to a macrophage-activating factor (GcMAF) by deglycosylation, enhancing immune responses. Polymorphisms in GC (rs7041, rs4588) are major determinants of circulating vitamin D levels and have been linked to various diseases.
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