GGCX: Gamma-Glutamyl Carboxylase
Key enzyme in vitamin K-dependent protein activation and coagulation
Gene Information Card
| Symbol | GGCX |
|---|---|
| Full Name | Gamma-glutamyl carboxylase |
| Gene Type | Protein coding |
| Chromosomal Location | 2p11.2 |
| NCBI Gene ID | 2678 ncbi.nlm.nih.gov/gene/2678 |
| Ensembl ID | ENSG00000115486 |
| UniProt ID | P38435 |
| OMIM ID | 137167 |
| HGNC ID | 4247 |
| Aliases | GC, VKCFD1, vitamin K-dependent gamma-glutamyl carboxylase |
Description
GGCX encodes gamma-glutamyl carboxylase, an endoplasmic reticulum enzyme that post-translationally converts specific glutamic acid residues to gamma-carboxyglutamic acid (Gla) in vitamin K-dependent proteins. This modification is essential for the biological activity of coagulation factors II, VII, IX, X, and anticoagulant proteins C and S, as well as other Gla-containing proteins involved in bone metabolism and vascular health.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Vitamin K-dependent clotting factor deficiency 1 (VKCFD1) | Loss-of-function mutations in GGCX impair carboxylation of coagulation factors, leading to reduced activity of factors II, VII, IX, X and bleeding diathesis. | ClinVar, OMIM |
| Pseudoxanthoma elasticum (PXE)-like disorder | Missense mutations in GGCX disrupt carboxylation of matrix Gla protein (MGP), causing ectopic calcification of elastic fibers in skin, eyes, and vessels. | OMIM, NCBI |
| Warfarin sensitivity | Polymorphisms in GGCX affect enzyme activity and vitamin K recycling, altering individual response to warfarin anticoagulation therapy. | ClinVar, NCBI |
| Retinopathy of prematurity | GGCX variants may influence vitamin K-dependent protein function in retinal vascular development. | NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 23.4 | High |
| Kidney | 12.1 | Medium |
| Lung | 9.8 | Medium |
| Heart | 6.5 | Low |
| Brain | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 18.7 | Hepatocyte-derived, high expression |
| HEK293 | 11.3 | Embryonic kidney, moderate expression |
| A549 | 7.1 | Lung carcinoma, low expression |
| K562 | 4.5 | Leukemia, low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.763G>A (p.Gly255Arg) | Missense | Rare | Loss of carboxylase activity; associated with VKCFD1 |
| c.1193G>A (p.Arg398Gln) | Missense | Rare | Impaired MGP carboxylation; PXE-like phenotype |
| c.974G>A (p.Arg325Gln) | Missense | Rare | Reduced enzyme function; warfarin sensitivity |
| c.1216C>T (p.Arg406Trp) | Missense | Rare | Dominant-negative effect; severe VKCFD1 |
Mutation functional classification
Loss of Function (LOF)
Most VKCFD1-associated mutations (e.g., p.Gly255Arg) reduce or abolish carboxylase activity, leading to undercarboxylated coagulation factors and bleeding.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in GGCX.
Dominant Negative (DN)
p.Arg406Trp is proposed to exert a dominant-negative effect by interfering with wild-type enzyme dimerization or substrate binding.
View complete mutation data：
Gene Ontology (GO)
| • gamma-glutamyl carboxylase activity (GO:0004596) | • endoplasmic reticulum (GO:0005783) |
| • blood coagulation (GO:0007596) | • peptidyl-glutamic acid carboxylation (GO:0017187) |
| • calcium ion binding (GO:0005509) |
Pathways
• Vitamin K metabolism and gamma-carboxylation (Reactome: R-HSA-159740)
• Formation of fibrin clot (clotting cascade) (Reactome: R-HSA-140877)
• Gamma-carboxylation of protein precursors (Reactome: R-HSA-159854)
Protein Summary
Gamma-glutamyl carboxylase (UniProt P38435) is a 758-amino acid transmembrane protein localized to the endoplasmic reticulum. It catalyzes the vitamin K-dependent carboxylation of glutamic acid residues to gamma-carboxyglutamic acid (Gla) in target proteins. The enzyme requires reduced vitamin K (KH2) as a cofactor and is inhibited by warfarin. Defects in GGCX cause bleeding disorders and ectopic calcification syndromes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GGCX Knockout HEK293 Cell Line | EDJ-KQ4703 | Human | 2677 | Details Get a Quote |
| GGCX Knockout A-549 Cell Line | EDJ-KQ27414 | Human | 2677 | Details Get a Quote |
| GGCX Knockout HCT 116 Cell Line | EDJ-KQ27415 | Human | 2677 | Details Get a Quote |
| GGCX Knockout HeLa Cell Line | EDJ-KQ27416 | Human | 2677 | Details Get a Quote |
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