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GGCX gamma-glutamyl carboxylase [ Homo sapiens (human) ]

Gene ID: 2677, updated on 3-Apr-2024

Summary

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Official Symbol
GGCXprovided by HGNC
Official Full Name
gamma-glutamyl carboxylaseprovided by HGNC
Primary source
HGNC:HGNC:4247
See related
Ensembl:ENSG00000115486 MIM:137167; AllianceGenome:HGNC:4247
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
VKCFD1
Summary
This gene encodes an integral membrane protein of the rough endoplasmic reticulum that carboxylates glutamate residues of vitamin K-dependent proteins to gamma carboxyl glutamate, a modification that is required for their activity. The vitamin K-dependent protein substrates have a propeptide that binds the enzyme, with carbon dioxide, dioxide, and reduced vitamin K acting as co-substrates. Vitamin K-dependent proteins affect a number of physiologic processes including blood coagulation, prevention of vascular calcification, and inflammation. Allelic variants of this gene have been associated with pseudoxanthoma elasticum-like disorder with associated multiple coagulation factor deficiency. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]
Expression
Ubiquitous expression in liver (RPKM 18.5), thyroid (RPKM 16.4) and 25 other tissues See more
Orthologs
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Genomic context

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Location:
2p11.2
Exon count:
15
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (85544720..85561493, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (85546779..85563552, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (85771843..85788616, complement)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene ribosomal protein SA pseudogene 22 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:85740471-85740650 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:85754312-85754503 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16127 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16128 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16129 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11701 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11702 Neighboring gene promoter of MAT2A antisense radiation-induced circulating long non-coding RNA Neighboring gene methionine adenosyltransferase 2A Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16130 Neighboring gene NANOG hESC enhancer GRCh37_chr2:85793997-85794515 Neighboring gene RNA, 7SL, cytoplasmic 126, pseudogene Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16131 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16132 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16133 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:85806777-85807430 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:85807431-85808085 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:85808086-85808739 Neighboring gene vesicle associated membrane protein 8

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. [Partial research progress of GGCX pathogenic variation associated phenotypes]. Shen G, et al. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 2022 Jun 10. PMID 35773773
  2. GGCX variants leading to biallelic deficiency to γ-carboxylate GRP cause skin laxity in VKCFD1 patients. Ghosh S, et al. Hum Mutat, 2022 Jan. PMID 34816548
  3. γ-Glutamyl carboxylase mutations differentially affect the biological function of vitamin K-dependent proteins. Hao Z, et al. Blood, 2021 Jan 28. PMID 33507293, Free PMC Article
  4. Pseudoxanthoma elasticum-like syndrome with coagulation deficiency associated with carotid artery hypoplasia and a novel gamma-glutamyl carboxylase gene mutation. Guillen-Climent S, et al. Int J Dermatol, 2021 Jan. PMID 32808310
  5. Effect of GGCX on the differentiation function of osteoporosis bone marrow mesenchymal stem cells through regulating TGFβ/smad signaling pathway. Wang QL, et al. Eur Rev Med Pharmacol Sci, 2019 Sep. PMID 31539109

See all (129) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke.
    Title: Association among VKORC1 rs9923231, CYP4F2 rs2108622, GGCX rs11676382 polymorphisms and acute ischemic stroke.
  2. [Partial research progress of GGCX pathogenic variation associated phenotypes].
    Title: [Partial research progress of GGCX pathogenic variation associated phenotypes].
  3. GGCX variants leading to biallelic deficiency to gamma-carboxylate GRP cause skin laxity in VKCFD1 patients.
    Title: GGCX variants leading to biallelic deficiency to γ-carboxylate GRP cause skin laxity in VKCFD1 patients.
  4. Pseudoxanthoma elasticum-like syndrome with coagulation deficiency associated with carotid artery hypoplasia and a novel gamma-glutamyl carboxylase gene mutation.
    Title: Pseudoxanthoma elasticum-like syndrome with coagulation deficiency associated with carotid artery hypoplasia and a novel gamma-glutamyl carboxylase gene mutation.
  5. gamma-Glutamyl carboxylase mutations differentially affect the biological function of vitamin K-dependent proteins.
    Title: γ-Glutamyl carboxylase mutations differentially affect the biological function of vitamin K-dependent proteins.
  6. Effect of GGCX on the differentiation function of osteoporosis bone marrow mesenchymal stem cells through regulating TGFbeta/smad signaling pathway.
    Title: Effect of GGCX on the differentiation function of osteoporosis bone marrow mesenchymal stem cells through regulating TGFβ/smad signaling pathway.
  7. Exon 2 skipping eliminates gamma-glutamyl carboxylase activity, indicating a partial splicing defect in a patient with vitamin K clotting factor deficiency.
    Title: Exon 2 skipping eliminates γ-glutamyl carboxylase activity, indicating a partial splicing defect in a patient with vitamin K clotting factor deficiency.
  8. The risk for ischemic atherothrombotic stroke in patients with the gamma-glutamyl carboxylase T/T genotype was higher than in major C-allele carriers.
    Title: [ANALYSIS OF γ-GLUTAMYL CARBOXYLASE GENE rs2592551 POLYMORPHISM ASSOCIATION WITH ISCHEMIC ATHEROTHROMBOTIC STROKE].
  9. unlike the traditional in vitro GGCX activity assay, allows us to assess the functionality of GGCX using its natural protein substrates in a cellular milieu
    Title: Splice-Site Mutation of Exon 3 Deletion in the Gamma-Glutamyl Carboxylase Gene Causes Inactivation of the Enzyme.
  10. 2 causative GGCX mutations ( c.1889-6G>A and c.1657delA) from the first reported clinical case of a VKCFD patient. The intronic mutation c.1889-6G>A affects GGCX splicing. Functional characterization of these 2 mutations suggests that truncation of GGCX from its C-terminus affects not only substrate binding but also protein stability.
    Title: Molecular basis of the first reported clinical case of congenital combined deficiency of coagulation factors.
Submit: New GeneRIF Correction See all GeneRIFs (61)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Seven prostate cancer susceptibility loci identified by a multi-stage genome-wide association study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • FLJ26629

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables gamma-glutamyl carboxylase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables gamma-glutamyl carboxylase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables gamma-glutamyl carboxylase activity TAS
Traceable Author Statement
more info
  
enables vitamin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in blood coagulation TAS
Traceable Author Statement
more info
 PubMed 
involved_in peptidyl-glutamic acid carboxylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in protein modification process TAS
Traceable Author Statement
more info
 PubMed 
involved_in vitamin K metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
is_active_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
located_in membrane TAS
Traceable Author Statement
more info
 PubMed 

General protein information

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Preferred Names
vitamin K-dependent gamma-carboxylase
Names
peptidyl-glutamate 4-carboxylase
NP_000812.2
NP_001135741.1
NP_001298241.1
XP_005264316.1
XP_016859292.1
XP_047299875.1
XP_047299876.1
XP_054197353.1
XP_054197354.1
XP_054197355.1
XP_054197356.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011811.2 RefSeqGene

    Range
    5042..21815
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_592

mRNA and Protein(s)

  1. NM_000821.7 → NP_000812.2  vitamin K-dependent gamma-carboxylase isoform 1

    See identical proteins and their annotated locations for NP_000812.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC016753, BC013979, BM974022, BQ000150, DC296316
    Consensus CDS
    CCDS1978.1
    UniProtKB/Swiss-Prot
    B4DMC5, E9PEE1, P38435, Q14415, Q6GU45
    UniProtKB/TrEMBL
    A7YA96
    Related
    ENSP00000233838.3, ENST00000233838.9
    Conserved Domains (1) summary
    pfam05090
    Location:66 → 502
    VKG_Carbox; Vitamin K-dependent gamma-carboxylase

  2. NM_001142269.4 → NP_001135741.1  vitamin K-dependent gamma-carboxylase isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region compared to variant 1. It encodes isoform 2, which is shorter than isoform 1.
    Source sequence(s)
    AC016753, AK297397, BC013979, BM974022, BQ000150, DC296316
    Consensus CDS
    CCDS46353.1
    UniProtKB/TrEMBL
    A7YA96
    Related
    ENSP00000408045.3, ENST00000430215.7
    Conserved Domains (2) summary
    smart00752
    Location:15 → 258
    HTTM; Horizontally Transferred TransMembrane Domain
    pfam05090
    Location:15 → 445
    VKG_Carbox; Vitamin K-dependent gamma-carboxylase

  3. NM_001311312.2 → NP_001298241.1  vitamin K-dependent gamma-carboxylase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks lacks several exons and its 3' terminal exon extends past a splice site that is used in variant 1. This results in a novel 3' coding region and 3' UTR compared to variant 1. It encodes isoform 3, which is shorter and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    AC016753, BM704752
    Consensus CDS
    CCDS92792.1
    UniProtKB/TrEMBL
    A0A8I5KZ18, A0A8I5QJA4
    Related
    ENSP00000508856.1, ENST00000496962.2
    Conserved Domains (1) summary
    cl02773
    Location:56 → 125
    HTTM; Horizontally Transferred TransMembrane Domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    85544720..85561493 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017003803.3 → XP_016859292.1  vitamin K-dependent gamma-carboxylase isoform X2

    UniProtKB/TrEMBL
    A7YA96

  2. XM_005264259.6 → XP_005264316.1  vitamin K-dependent gamma-carboxylase isoform X1

    UniProtKB/TrEMBL
    A7YA96
    Conserved Domains (2) summary
    smart00752
    Location:56 → 315
    HTTM; Horizontally Transferred TransMembrane Domain
    pfam05090
    Location:66 → 502
    VKG_Carbox; Vitamin K-dependent gamma-carboxylase

  3. XM_047443919.1 → XP_047299875.1  vitamin K-dependent gamma-carboxylase isoform X3

    Related
    ENSP00000510264.1, ENST00000693287.1

  4. XM_047443920.1 → XP_047299876.1  vitamin K-dependent gamma-carboxylase isoform X4

    Related
    ENSP00000509369.1, ENST00000691348.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    85546779..85563552 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054341379.1 → XP_054197354.1  vitamin K-dependent gamma-carboxylase isoform X2

  2. XM_054341378.1 → XP_054197353.1  vitamin K-dependent gamma-carboxylase isoform X1

  3. XM_054341380.1 → XP_054197355.1  vitamin K-dependent gamma-carboxylase isoform X3

  4. XM_054341381.1 → XP_054197356.1  vitamin K-dependent gamma-carboxylase isoform X4

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P38435.2 GenPept UniProtKB/Swiss-Prot:P38435

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