Property Summary

NCBI Gene PubMed Count 86
PubMed Score 72.75
PubTator Score 108.98

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (5)

Expression

  Differential Expression (20)

Disease log2 FC p
gastric cancer 1.100 6.9e-03
pancreatic cancer 1.100 5.8e-03
Waldenstrons macroglobulinemia 1.160 1.7e-02
Multiple myeloma 1.205 9.4e-03
psoriasis -6.400 3.3e-06
osteosarcoma -5.501 3.5e-12
posterior fossa group A ependymoma 1.300 4.3e-11
astrocytoma 1.700 5.8e-03
atypical teratoid / rhabdoid tumor -1.100 3.0e-03
glioblastoma -1.400 2.3e-04
medulloblastoma, large-cell -1.600 1.7e-04
pancreatic ductal adenocarcinoma liver m... -2.648 5.7e-04
tuberculosis and treatment for 6 months -1.100 2.7e-05
non-small cell lung cancer 1.040 2.7e-09
lung cancer 1.800 3.3e-02
group 3 medulloblastoma 1.300 1.6e-03
pancreatic carcinoma 1.100 5.8e-03
lung adenocarcinoma 1.363 2.1e-04
invasive ductal carcinoma 1.100 1.4e-02
ovarian cancer 2.100 7.6e-05

 GWAS Trait (1)

Protein-protein Interaction (4)

Gene RIF (67)

PMID Text
26751406 529 adults (n = 325 European-Americans, 204 Egyptians) on a stable warfarin dose were genotyped for GGCX rs12714145 and rs10654848, FPGS rs7856096, and STX1B rs4889606.
25151188 Detected are ten mutations in the gamma-glutamyl carboxylase gene in patients with hereditary deficiency of vitamin K-dependent coagulation factors.
25042728 GGCX c.2084+45G polymorphisms has a moderate effect on VKAs dose requirements in Slavic population from Central-Eastern Europe.
24927344 The allele frequency for GGCX 12970 C > G is 1.43 in north Indians and did not have a significant bearing on the maintenance dose of acenocoumarol oral anticoagulant in cardiac valve replacement patients.
24739904 GGCX mutation found in families with pseudoxanthoma elasticum with retinitis pigmentosa and cutis laxa.
24231026 study demonstrated the effects of SNP (974G>A) in the GGCX gene on the correlation between dietary vitamin K intake and gamma-carboxylation of serum osteocalcin
24148610 In atrial fibrillation population in Xinjiang, patients with CT and TT genotypes in the gamma-glutamyl carboxylase gene rs259251 loci required significantly higher warfarin dose than those with CC genotype.
23941071 These findings indicate that individuals carrying the CYP2C19 rs3814637CC or CYP2C9 rs1057910AA or GGCX rs699664AA genotype needed higher warfarin doses in the Chinese population.
23817635 evaluation of urinary Gla excretion in relation with apo E genotype
22188360 Quantitative PCR assays for VKORC1, CYP4F2, GGCX and CALU identified two copies in all populations.
21800014 no association between haplotypes and venous thrombosis
21704322 Molecular analysis of the gamma-glutamylcarboxylase gene revealed a heterozygous single nucleotide polymorphism, which decreases carboxylase activity and induces VK-dependent coagulation deficiency.
21475774 no effects of genetic variants on maintenance warfarin dose in a multi-ethnic Asian population
21344298 GGCX polymorphism appeared to have an influence over the reduction of undercarboxylated osteocalcin, especially in older women (age >/=65).
21057703 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20811787 Observational study of gene-disease association. (HuGE Navigator)
20716530 Effect of vitamin K-dependent protein precursor propeptide, vitamin K hydroquinone, and glutamate substrate binding on the structure and function of {gamma}-glutamyl carboxylase.
20716240 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20694283 genetic polymorphism affects therapeutic dose of warfarin
20694283 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20332604 The activity and expression of GGCX are decreased in renal tissues of patients with calcium oxolate urolithiasis.
20193673 Subtle polymorphisms, including those in GGCX, NQO1, and VKORC1 genes, influence individual susceptibility to the development of atherosclerotic stroke.
20193673 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20149073 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20020283 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19958090 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19942260 Gene polymorphisms of VKORC1 significantly associated with the variation of interindividual warfarin dose requirement variation, and the effects are different in ethnicities.
19913121 Observational study of gene-disease association. (HuGE Navigator)
19821094 there may be no significant association between the low activity and mutation of GGCX in calcium oxalate urolithiasis
19821094 Observational study of gene-disease association. (HuGE Navigator)
19794411 Observational study of gene-disease association, gene-gene interaction, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
19652895 Polymorphisms in VKORC1 and GGCX are not major genetic determinants of vitamin K-dependent coagulation factor activity in Western Germans.
19652895 Observational study of gene-disease association. (HuGE Navigator)
19436136 heterozygous carriers of GGCX rs10187424 and rs7568458 had significantly lower percent undercarboxylated osteocalcin relative to either homozygous group.
19383345 exon 2 deletion splice variant of GGCX causes dysfunction of GGCX enzyme activity resulting in des-gamma-carboxy prothrombin production in HCC cell lines
19233910 Observational study of genetic testing. (HuGE Navigator)
19116367 Our findings also confirm GGCX as the second gene locus causing Pseudoxanthoma elasticum
18800149 analysis of GGCX and ABCC6 mutations in a family with pseudoxanthoma elasticum-like phenotypes [case report]
18680736 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
18498174 A homology model of gamma-glutamyl carboxylase transmembrane domains 2 and 5 suggests that not only do these two domains associate but that transmembrane domain 2 may interact with another transmembrane domain.
18234294 GGCX R325Q genotype did not provide significant differences in acenocoumarol dose requirements in patients
18079608 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
17786385 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17786385 There is no significant association between the polymorphisms in GGCX and the warfarin dose requirement.
17764537 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17764537 identified 37 SNPs in GGCX. The GGCX-12970 SNP had a small, but significant effect, on warfarin maintenance dose
17189218 Observational study of gene-disease association. (HuGE Navigator)
17144668 Mass spectrometric results show that the N-linked glycosylation in carboxylase occurs at positions N459, N550, N605, and N627.
17049586 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17049586 In addition to polymorphisms in VKORC1 and CYP2C9, we identified GGCX 8016G>A, resulting in the missense mutation R325Q, as a genetic determinant of warfarin maintenance dose in Japanese patients.
17048007 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
17029979 Observational study of gene-disease association. (HuGE Navigator)
17029979 report demonstrates the different activities of GGCX between the common genotypes and their association with bone mineral density
16979907 Crystallization of human GGCX.
16676068 Observational study of gene-disease association. (HuGE Navigator)
15900282 Observational study of gene-disease association. (HuGE Navigator)
15883587 Observational study of gene-disease association and pharmacogenomic / toxicogenomic. (HuGE Navigator)
15883587 GGCX SNP showed a small but significant effect on warfarin dose.
15365175 An activated amine initiates the vitamin K-dependent carboxylation reaction, while the Cys-99 and Cys-450 free sulfhydryls play other important roles in the carboxylase reaction
15365175 Quantitative radiolabeled N-ethylmaleimide modification of a carboxylase with all Cys residues changed to Ala supports the identification of Cys-99 and Cys-450 as the free sulfhydryls in the active site.
14660587 binding of the factor IX gamma-carboxyglutamic acid domain to the vitamin K-dependent gamma-glutamyl carboxylase active site has a role in carboxylation and regulation of release of carboxylated product
14567538 A 14-base deletion was found in intron 1 (bases 1056-1069) of the gamma-carboxylase gene. It destroys a reverse palindromic sequence (TTGAGGCAA) of the type often associated with cis-acting elements. This element may regulation the enzyme's expression.
12968027 mutations in residues between 393 and 404 in gamma-glutamyl carboxylase cause impaired glutamate binding
12963724 Cys-99 and Cys-450 form the only disulfide bond in carboxylase
12034728 characterization of vitamin K-dependent gamma-glutamyl carboxylase internal propeptide
11087858 Cys-99 and Cys-450 are free sulfhydryls in the gamma-glutamyl carboxylase active site. The free sulfhydryls were mapped by isolating a native carboxylase-factor IX enzyme substrate complex, modification with NEM and mass spectral mapping.

AA Sequence

MAVSAGSARTSPSSDKVQKDKAELISGPRQDSRIGKLLGFEWTDLSSWRRLVTLLNRPTDPASLAVFRFL      1 - 70
FGFLMVLDIPQERGLSSLDRKYLDGLDVCRFPLLDALRPLPLDWMYLVYTIMFLGALGMMLGLCYRISCV     71 - 140
LFLLPYWYVFLLDKTSWNNHSYLYGLLAFQLTFMDANHYWSVDGLLNAHRRNAHVPLWNYAVLRGQIFIV    141 - 210
YFIAGVKKLDADWVEGYSMEYLSRHWLFSPFKLLLSEELTSLLVVHWGGLLLDLSAGFLLFFDVSRSIGL    211 - 280
FFVSYFHCMNSQLFSIGMFSYVMLASSPLFCSPEWPRKLVSYCPRRLQQLLPLKAAPQPSVSCVYKRSRG    281 - 350
KSGQKPGLRHQLGAAFTLLYLLEQLFLPYSHFLTQGYNNWTNGLYGYSWDMMVHSRSHQHVKITYRDGRT    351 - 420
GELGYLNPGVFTQSRRWKDHADMLKQYATCLSRLLPKYNVTEPQIYFDIWVSINDRFQQRIFDPRVDIVQ    421 - 490
AAWSPFQRTSWVQPLLMDLSPWRAKLQEIKSSLDNHTEVVFIADFPGLHLENFVSEDLGNTSIQLLQGEV    491 - 560
TVELVAEQKNQTLREGEKMQLPAGEYHKVYTTSPSPSCYMYVYVNTTELALEQDLAYLQELKEKVENGSE    561 - 630
TGPLPPELQPLLEGEVKGGPEPTPLVQTFLRRQQRLQEIERRRNTPFHERFFRFLLRKLYVFRRSFLMTC    631 - 700
ISLRNLILGRPSLEQLAQEVTYANLRPFEAVGELNPSNTDSSHSNPPESNPDPVHSEF                701 - 758
//

Text Mined References (93)

PMID Year Title
26751406 2016 Impact of GGCX, STX1B and FPGS Polymorphisms on Warfarin Dose Requirements in European-Americans and Egyptians.
25151188 2014 Bleeding and non-bleeding phenotypes in patients with GGCX gene mutations.
25042728 2014 Genetic determinants of acenocoumarol and warfarin maintenance dose requirements in Slavic population: a potential role of CYP4F2 and GGCX polymorphisms.
24927344 2014 CYP4F2 1347 G > A & GGCX 12970 C > G polymorphisms: frequency in north Indians & their effect on dosing of acenocoumarol oral anticoagulant.
24739904 2014 Retinitis pigmentosa, cutis laxa, and pseudoxanthoma elasticum-like skin manifestations associated with GGCX mutations.
24275569 2014 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24231026 2013 Effects of gamma-glutamyl carboxylase gene polymorphism (R325Q) on the association between dietary vitamin K intake and gamma-carboxylation of osteocalcin in young adults.
24148610 2013 Association of GGCX gene polymorphism with warfarin dose in atrial fibrillation population in Xinjiang.
23941071 2013 Association of genetic polymorphisms with warfarin dose requirements in Chinese patients.
23817635 2013 Apolipoprotein E genotype may influence urinary gammacarboxyglutamate (Gla) concentrations in young individuals.
22188360 2012 Copy number variation and warfarin dosing: evaluation of CYP2C9, VKORC1, CYP4F2, GGCX and CALU.
21800014 2011 Haplotypes of VKORC1, NQO1 and GGCX, their effect on activity levels of vitamin K-dependent coagulation factors, and the risk of venous thrombosis.
21743467 2011 Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.
21704322 2011 Functional polymorphism in gamma-glutamylcarboxylase is a risk factor for severe neonatal hemorrhage.
21475774 2011 Effects of CYP4F2 and GGCX genetic variants on maintenance warfarin dose in a multi-ethnic Asian population.
21406692 2011 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21344298 2011 Effect of GGCX gene polymorphism on the responses of serum undercarboxylated osteocalcin and bone turnover markers after treatment with vitamin K2 (menatetrenone) among postmenopausal Thai women.
21057703 2011 Impact of pharmacokinetic (CYP2C9) and pharmacodynamic (VKORC1, F7, GGCX, CALU, EPHX1) gene variants on the initiation and maintenance phases of phenprocoumon therapy.
20811787 2010 The association of protein S Tokushima-K196E with a risk of deep vein thrombosis.
20716530 2010 Effect of vitamin K-dependent protein precursor propeptide, vitamin K hydroquinone, and glutamate substrate binding on the structure and function of {gamma}-glutamyl carboxylase.
20716240 2010 New genetic variant that might improve warfarin dose prediction in African Americans.
20694283 2010 Gamma-glutamyl carboxylase and its influence on warfarin dose.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20332604 2010 Activity and expression of vitamin K-dependent gamma-glutamyl carboxylase in patients with calcium oxalate urolithiasis.
20213530 2010 High-level expression of functional recombinant human coagulation factor VII in insect cells.
20193673 2010 Genotype polymorphisms of GGCX, NQO1, and VKORC1 genes associated with risk susceptibility in patients with large-artery atherosclerotic stroke.
20149073 2010 Pharmacogenetics of acenocoumarol in patients with extreme dose requirements.
20020283 2010 Genetic determinants of acenocoumarol and phenprocoumon maintenance dose requirements.
19958090 2009 Genetic determinants of warfarin dosing in the Han-Chinese population.
19942260 2010 Impact of VKORC1 gene polymorphism on interindividual and interethnic warfarin dosage requirement--a systematic review and meta analysis.
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19821094 2009 Genetic mutation of vitamin K-dependent gamma-glutamyl carboxylase domain in patients with calcium oxalate urolithiasis.
19794411 2010 Genetic factors (VKORC1, CYP2C9, EPHX1, and CYP4F2) are predictor variables for warfarin response in very elderly, frail inpatients.
19652895 2009 Polymorphisms in VKORC1 and GGCX are not major genetic determinants of vitamin K-dependent coagulation factor activity in Western Germans.
19436136 2009 Association of sequence variations in vitamin K epoxide reductase and gamma-glutamyl carboxylase genes with biochemical measures of vitamin K status.
19413330 2009 Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.
19383345 2008 Exon 2 deletion splice variant of gamma-glutamyl carboxylase causes des-gamma-carboxy prothrombin production in hepatocellular carcinoma cell lines.
19233910 2009 A multiplex assay for detecting genetic variations in CYP2C9, VKORC1, and GGCX involved in warfarin metabolism.
19159218 2009 Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.
19116367 2009 Co-existent pseudoxanthoma elasticum and vitamin K-dependent coagulation factor deficiency: compound heterozygosity for mutations in the GGCX gene.
18800149 2009 Mutations in the GGCX and ABCC6 genes in a family with pseudoxanthoma elasticum-like phenotypes.
18680736 2008 Genetic factors contribute to patient-specific warfarin dose for Han Chinese.
18498174 2008 Transmembrane domain interactions and residue proline 378 are essential for proper structure, especially disulfide bond formation, in the human vitamin K-dependent gamma-glutamyl carboxylase.
18234294 2008 Gamma-glutamyl carboxylase R325Q polymorphism on the response of acenocoumarol.
18079608 2007 Nutritional effects of gamma-glutamyl carboxylase gene polymorphism on the correlation between the vitamin K status and gamma-carboxylation of osteocalcin in young males.
17786385 2007 High-resolution SNP and haplotype maps of the human gamma-glutamyl carboxylase gene (GGCX) and association study between polymorphisms in GGCX and the warfarin maintenance dose requirement of the Japanese population.
17764537 2007 Gamma-glutamyl carboxylase (GGCX) tagSNPs have limited utility for predicting warfarin maintenance dose.
17189218 2006 Polymorphisms in vitamin K-dependent gamma-carboxylation-related genes influence interindividual variability in plasma protein C and protein S activities in the general population.
17144668 2006 Identification of the N-linked glycosylation sites of vitamin K-dependent carboxylase and effect of glycosylation on carboxylase function.
17110937 2007 Pseudoxanthoma elasticum-like phenotype with cutis laxa and multiple coagulation factor deficiency represents a separate genetic entity.
17073445 2006 Brønsted analysis reveals Lys218 as the carboxylase active site base that deprotonates vitamin K hydroquinone to initiate vitamin K-dependent protein carboxylation.
17049586 2007 Genotypes of vitamin K epoxide reductase, gamma-glutamyl carboxylase, and cytochrome P450 2C9 as determinants of daily warfarin dose in Japanese patients.
17048007 2007 Association of warfarin dose with genes involved in its action and metabolism.
17029979 2007 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.
16979907 2007 Two-dimensional crystallization of human vitamin K-dependent gamma-glutamyl carboxylase.
16676068 2006 The influence of sequence variations in factor VII, gamma-glutamyl carboxylase and vitamin K epoxide reductase complex genes on warfarin dose requirement.
16011462 2005 The vitamin K-dependent carboxylase.
15900282 2005 Common genetic variants of microsomal epoxide hydrolase affect warfarin dose requirements beyond the effect of cytochrome P450 2C9.
15883587 2005 Common VKORC1 and GGCX polymorphisms associated with warfarin dose.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15365175 2004 A new model for vitamin K-dependent carboxylation: the catalytic base that deprotonates vitamin K hydroquinone is not Cys but an activated amine.
15287948 2004 Compound heterozygous mutations in the gamma-glutamyl carboxylase gene cause combined deficiency of all vitamin K-dependent blood coagulation factors.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14660587 2004 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.
14567538 2003 Four factor deficiency.
12968027 2003 A conserved region of human vitamin K-dependent carboxylase between residues 393 and 404 is important for its interaction with the glutamate substrate.
12963724 2003 Determination of disulfide bond assignment of human vitamin K-dependent gamma-glutamyl carboxylase by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12475254 2002 Carboxylase overexpression effects full carboxylation but poor release and secretion of factor IX: implications for the release of vitamin K-dependent proteins.
12034728 2002 The putative vitamin K-dependent gamma-glutamyl carboxylase internal propeptide appears to be the propeptide binding site.
11591726 2001 Identification of sequences within the gamma-carboxylase that represent a novel contact site with vitamin K-dependent proteins and that are required for activity.
11580082 2001 1,25-Dihydroxyvitamin D3 promotes vitamin K2 metabolism in human osteoblasts.
11570873 2001 A novel fluorescence assay to study propeptide interaction with gamma-glutamyl carboxylase.
11133752 2001 Posttranslational modifications of recombinant myotube-synthesized human factor IX.
11087858 2000 Identification of the vitamin K-dependent carboxylase active site: Cys-99 and Cys-450 are required for both epoxidation and carboxylation.
11071668 2000 Novel mutation in the gamma-glutamyl carboxylase gene resulting in congenital combined deficiency of all vitamin K-dependent blood coagulation factors.
10934213 2000 Expression and characterization of the naturally occurring mutation L394R in human gamma-glutamyl carboxylase.
10910912 2000 A topological study of the human gamma-glutamyl carboxylase.
10556651 1999 Process of carboxylation of glutamic acid residues in the gla domain of human des-gamma-carboxyprothrombin.
10393081 1999 Osteocalcin binds tightly to the gamma-glutamylcarboxylase at a site distinct from that of the other known vitamin K-dependent proteins.
9845520 1998 A missense mutation in gamma-glutamyl carboxylase gene causes combined deficiency of all vitamin K-dependent blood coagulation factors.
9538022 1998 Structure/function analyses of recombinant variants of human factor Xa: factor Xa incorporation into prothrombinase on the thrombin-activated platelet surface is not mimicked by synthetic phospholipid vesicles.
9166845 1997 Genomic sequence and transcription start site for the human gamma-glutamyl carboxylase.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.
8702425 1996 Vitamin K-dependent carboxylase: mRNA distribution and effects of vitamin K-deficiency and warfarin treatment.
8647260 1996 Site-directed mutagenesis but not gamma-carboxylation of Glu-35 in factor VIIa affects the association with tissue factor.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.
7759116 1995 Chromosomal localization of the gamma-glutamyl carboxylase gene at 2p12.
3944102 1986 Distribution of gamma-carboxyglutamic acid residues in partially carboxylated human prothrombins.
2145029 1990 Hereditary deficiency of all vitamin K-dependent procoagulants and anticoagulants.
1749935 1991 Cloning and expression of the cDNA for human gamma-glutamyl carboxylase.
1498334 1992 Role of individual gamma-carboxyglutamic acid residues of activated human protein C in defining its in vitro anticoagulant activity.