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Gene Review

GGCX  -  gamma-glutamyl carboxylase

Homo sapiens

Synonyms: GC, Gamma-glutamyl carboxylase, Peptidyl-glutamate 4-carboxylase, VKCFD1, Vitamin K gamma glutamyl carboxylase, ...
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Disease relevance of GGCX


High impact information on GGCX


Biological context of GGCX


Anatomical context of GGCX


Associations of GGCX with chemical compounds

  • In addition, one GGCX SNP showed a small but significant effect on warfarin dose [18].
  • Carboxylation is accomplished by the enzyme gamma glutamyl carboxylase (GGCX) which requires the propeptide-containing substrate and three co-substrates: reduced vitamin K, CO2, and O2 [19].
  • Propeptides of the vitamin K-dependent proteins bind to an exosite on gamma-glutamyl carboxylase; while they are bound, multiple glutamic acids in the gamma-carboxyglutamic acid (Gla) domain are carboxylated [20].
  • We conclude that, the potentiation of the oral anticoagulant effect by paracetamol is likely to result from NAPQI-induced inhibition of enzymes of the vitamin K cycle, particularly VKD-carb [21].
  • NAPQI, on the other hand, appeared to interfere with VKD carb activity via two mechanisms; 1) oxidation of the cofactor vitamin K-hydroquinone, 2) inactivation of the enzyme [21].

Other interactions of GGCX


Analytical, diagnostic and therapeutic context of GGCX

  • Individual kidney and total ERPF were determined from gamma camera (GC) methods using renal uptake 1-2 min after injection [24].
  • Two-dimensional crystallization of human vitamin K-dependent gamma-glutamyl carboxylase [25].
  • Isotopic analysis of the pentafluoropropionyl derivative of vitamin K(1) is performed by gas chromatography/mass spectrometry (GC/MS) [26].
  • Epidemiological studies have found that the increases in the risk of fracture in oral GC users are dose dependent and occur within three months of starting GC therapy [27].
  • Three different systems for the determination of radon in water have been examined: liquid scintillation counting (LSC), degassification followed by Lucas cell counting (LCC) and gamma counting (GC) [28].


  1. Sequence analysis and phylogenetic reconstruction of the genes encoding the large and small subunits of ribulose-1,5-bisphosphate carboxylase/oxygenase from the chlorophyll b-containing prokaryote Prochlorothrix hollandica. Morden, C.W., Golden, S.S. J. Mol. Evol. (1991) [Pubmed]
  2. Cloning and characterization of the 5' end and promoter region of the chicken acetyl-CoA carboxylase gene. El Khadir-Mounier, C., Le Fur, N., Powell, R.S., Diot, C., Langlois, P., Mallard, J., Douaire, M. Biochem. J. (1996) [Pubmed]
  3. Isolated 3-methylcrotonyl-CoA carboxylase deficiency in a 15-year-old girl. Murayama, K., Kimura, M., Yamaguchi, S., Shinka, T., Kodama, K. Brain Dev. (1997) [Pubmed]
  4. Decreased renal vitamin K-dependent gamma-glutamyl carboxylase activity in calcium oxalate calculi patients. Chen, J., Liu, J., Zhang, Y., Ye, Z., Wang, S. Chin. Med. J. (2003) [Pubmed]
  5. A Rac-cGMP Signaling Pathway. Guo, D., Tan, Y.C., Wang, D., Madhusoodanan, K.S., Zheng, Y., Maack, T., Zhang, J.J., Huang, X.Y. Cell (2007) [Pubmed]
  6. gamma -Glutamyl carboxylation: An extracellular posttranslational modification that antedates the divergence of molluscs, arthropods, and chordates. Bandyopadhyay, P.K., Garrett, J.E., Shetty, R.P., Keate, T., Walker, C.S., Olivera, B.M. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  7. Propeptide and glutamate-containing substrates bound to the vitamin K-dependent carboxylase convert its vitamin K epoxidase function from an inactive to an active state. Sugiura, I., Furie, B., Walsh, C.T., Furie, B.C. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  8. Compound heterozygosity of novel missense mutations in the gamma-glutamyl-carboxylase gene causes hereditary combined vitamin K-dependent coagulation factor deficiency. Darghouth, D., Hallgren, K.W., Shtofman, R.L., Mrad, A., Gharbi, Y., Maherzi, A., Kastally, R., LeRicousse, S., Berkner, K.L., Rosa, J.P. Blood (2006) [Pubmed]
  9. Gamma-glutamyl carboxylase (GGCX) microsatellite and warfarin dosing. Chen, L.Y., Eriksson, N., Gwilliam, R., Bentley, D., Deloukas, P., Wadelius, M. Blood (2005) [Pubmed]
  10. Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors. Rost, S., Fregin, A., Koch, D., Compes, M., Müller, C.R., Oldenburg, J. Br. J. Haematol. (2004) [Pubmed]
  11. A functional single nucleotide polymorphism in the vitamin-K-dependent gamma-glutamyl carboxylase gene (Arg325Gln) is associated with bone mineral density in elderly Japanese women. Kinoshita, H., Nakagawa, K., Narusawa, K., Goseki-Sone, M., Fukushi-Irie, M., Mizoi, L., Yoshida, H., Okano, T., Nakamura, T., Suzuki, T., Inoue, S., Orimo, H., Ouchi, Y., Hosoi, T. Bone (2007) [Pubmed]
  12. Founder mutation Arg485Pro led to recurrent compound heterozygous GGCX genotypes in two German patients with VKCFD type 1. Rost, S., Geisen, C., Fregin, A., Seifried, E., Müller, C.R., Oldenburg, J. Blood Coagul. Fibrinolysis (2006) [Pubmed]
  13. A topological study of the human gamma-glutamyl carboxylase. Tie, J., Wu, S.M., Jin, D., Nicchitta, C.V., Stafford, D.W. Blood (2000) [Pubmed]
  14. 1,25-Dihydroxyvitamin D3 promotes vitamin K2 metabolism in human osteoblasts. Miyake, N., Hoshi, K., Sano, Y., Kikuchi, K., Tadano, K., Koshihara, Y. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. (2001) [Pubmed]
  15. Isolation and characterization of alkaliphilic, chemolithoautotrophic, sulphur-oxidizing bacteria. Sorokin, D.Y., Robertson, L.A., Kuenen, J.G. Antonie Van Leeuwenhoek (2000) [Pubmed]
  16. Reduction of glucocorticoid receptor ligand binding by the 11-beta hydroxysteroid dehydrogenase type 2 inhibitor, Thiram. Garbrecht, M.R., Krozowski, Z.S., Snyder, J.M., Schmidt, T.J. Steroids (2006) [Pubmed]
  17. Binding of GC (VDBP) to membranes of human B lymphocytes following stripping of extant protein. Petrini, M., Allegrini, A., Ambrogi, F., Valentini, P., Sabbatini, A., Arnaud, P., Galbraith, R.M. J. Endocrinol. Invest. (1995) [Pubmed]
  18. Common VKORC1 and GGCX polymorphisms associated with warfarin dose. Wadelius, M., Chen, L.Y., Downes, K., Ghori, J., Hunt, S., Eriksson, N., Wallerman, O., Melhus, H., Wadelius, C., Bentley, D., Deloukas, P. Pharmacogenomics J. (2005) [Pubmed]
  19. The vitamin K cycle. Stafford, D.W. J. Thromb. Haemost. (2005) [Pubmed]
  20. Binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K-dependent gamma-glutamyl carboxylase active site induces an allosteric effect that may ensure processive carboxylation and regulate the release of carboxylated product. Lin, P.J., Straight, D.L., Stafford, D.W. J. Biol. Chem. (2004) [Pubmed]
  21. Paracetamol (acetaminophen) warfarin interaction: NAPQI, the toxic metabolite of paracetamol, is an inhibitor of enzymes in the vitamin K cycle. Thijssen, H.H., Soute, B.A., Vervoort, L.M., Claessens, J.G. Thromb. Haemost. (2004) [Pubmed]
  22. Levels of vitamin K, immunoreactive prothrombin, des-gamma-carboxy prothrombin and gamma-glutamyl carboxylase activity in hepatocellular carcinoma tissue. Yamagata, H., Nakanishi, T., Furukawa, M., Okuda, H., Obata, H. J. Gastroenterol. Hepatol. (1995) [Pubmed]
  23. Association of pharmacokinetic (CYP2C9) and pharmacodynamic (factors II, VII, IX, and X; proteins S and C; and gamma-glutamyl carboxylase) gene variants with warfarin sensitivity. Shikata, E., Ieiri, I., Ishiguro, S., Aono, H., Inoue, K., Koide, T., Ohgi, S., Otsubo, K. Blood (2004) [Pubmed]
  24. Measurement of effective renal plasma flow: a comparison of methods. Fine, E.J., Axelrod, M., Gorkin, J., Saleemi, K., Blaufox, M.D. J. Nucl. Med. (1987) [Pubmed]
  25. Two-dimensional crystallization of human vitamin K-dependent gamma-glutamyl carboxylase. Schmidt-Krey, I., Haase, W., Mutucumarana, V., Stafford, D.W., Kühlbrandt, W. J. Struct. Biol. (2007) [Pubmed]
  26. Analysis of isotope ratios in vitamin K1 (phylloquinone) from human plasma by gas chromatography/mass spectrometry. Jones, K.S., Bluck, L.J., Coward, W.A. Rapid Commun. Mass Spectrom. (2006) [Pubmed]
  27. The pathogenesis, epidemiology and management of glucocorticoid-induced osteoporosis. van Staa, T.P. Calcif. Tissue Int. (2006) [Pubmed]
  28. Optimization and comparison of three different methods for the determination of Rn-222 in water. Belloni, P., Cavaioli, M., Ingrao, G., Mancini, C., Notaro, M., Santaroni, P., Torri, G., Vasselli, R. Sci. Total Environ. (1995) [Pubmed]
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