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G6PC2 glucose-6-phosphatase catalytic subunit 2 [ Homo sapiens (human) ]

Gene ID: 57818, updated on 2-Nov-2024

Summary

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Official Symbol
G6PC2provided by HGNC
Official Full Name
glucose-6-phosphatase catalytic subunit 2provided by HGNC
Primary source
HGNC:HGNC:28906
See related
Ensembl:ENSG00000152254 MIM:608058; AllianceGenome:HGNC:28906
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
IGRP
Summary
This gene encodes an enzyme belonging to the glucose-6-phosphatase catalytic subunit family. These enzymes are part of a multicomponent integral membrane system that catalyzes the hydrolysis of glucose-6-phosphate, the terminal step in gluconeogenic and glycogenolytic pathways, allowing the release of glucose into the bloodstream. The family member encoded by this gene is found in pancreatic islets and does not exhibit phosphohydrolase activity, but it is a major target of cell-mediated autoimmunity in diabetes. Several alternatively spliced transcript variants of this gene have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]
Expression
Biased expression in pancreas (RPKM 3.9), testis (RPKM 0.4) and 1 other tissue See more
Orthologs
mouse all
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Genomic context

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See G6PC2 in Genome Data Viewer
Location:
2q31.1
Exon count:
5
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (168901291..168910000)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (169375781..169384490)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (169757801..169766510)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene nitric oxide synthase trafficking Neighboring gene uncharacterized LOC124907904 Neighboring gene SPC25 component of NDC80 kinetochore complex Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:169764453-169765248 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:169769023-169769558 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:169769559-169770093 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:169791870-169793069 Neighboring gene ATP binding cassette subfamily B member 11 Neighboring gene Sharpr-MPRA regulatory region 4346 Neighboring gene dehydrogenase/reductase 9

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. Mutations in the third gene shown to alter fasting glucose levels in the population (G6PC2) are not a common cause of monogenic forms of pancreatic B-cell dysfunction. Edghill EL, et al. Diabet Med, 2009 Jan. PMID 19125775
  2. Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS). An P, et al. Metabolism, 2014 Apr. PMID 24405752, Free PMC Article
  3. Alternative splicing and differential expression of the islet autoantigen IGRP between pancreas and thymus contributes to immunogenicity of pancreatic islets but not diabetogenicity in humans. de Jong VM, et al. Diabetologia, 2013 Dec. PMID 24030068
  4. Multiple functional polymorphisms in the G6PC2 gene contribute to the association with higher fasting plasma glucose levels. Baerenwald DA, et al. Diabetologia, 2013 Jun. PMID 23508304, Free PMC Article
  5. HbA1c-based diabetes diagnosis among patients with glucokinase mutation (GCK-MODY) is affected by a genetic variant of glucose-6-phosphatase (G6PC2). Borowiec M, et al. Diabet Med, 2012 Nov. PMID 22486180

See all (72) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells.
    Title: Multiple promoter and enhancer differences likely contribute to augmented G6PC2 expression in human versus mouse pancreatic islet alpha cells.
  2. Identification of structural motifs critical for human G6PC2 function informed by sequence analysis and an AlphaFold2-predicted model.
    Title: Identification of structural motifs critical for human G6PC2 function informed by sequence analysis and an AlphaFold2-predicted model.
  3. G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.
    Title: G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.
  4. Additive genetic effect of GCKR, G6PC2, and SLC30A8 variants on fasting glucose levels and risk of type 2 diabetes.
    Title: Additive genetic effect of GCKR, G6PC2, and SLC30A8 variants on fasting glucose levels and risk of type 2 diabetes.
  5. Mutations in G6PC2 gene with increased risk for development of type 2 diabetes: Understanding via computational approach.
    Title: Mutations in G6PC2 gene with increased risk for development of type 2 diabetes: Understanding via computational approach.
  6. G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo.
    Title: G6PC indicated poor prognosis in cervical cancer and promoted cervical carcinogenesis in vitro and in vivo.
  7. Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose.
    Title: Multi-omics analysis identifies CpGs near G6PC2 mediating the effects of genetic variants on fasting glucose.
  8. Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11).
    Title: Haplotypes of the genes (GCK and G6PC2) underlying the glucose/glucose-6-phosphate cycle are associated with pancreatic beta cell glucose sensitivity in patients with newly diagnosed type 2 diabetes from the VNDS study (VNDS 11).
  9. Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose.
    Title: Pancreatic islet beta cell-specific deletion of G6pc2 reduces fasting blood glucose.
  10. The results suggest that the GCKR and G6PC2 genes may contribute to the risk of type 2 diabetes independently and/or in an interactive manner in the Han Chinese population.
    Title: Gene-gene interactions lead to higher risk for development of type 2 diabetes in a Chinese Han population: a prospective nested case-control study.
Submit: New GeneRIF Correction See all GeneRIFs (51)

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
A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance.
EBI GWAS Catalog
A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels.
EBI GWAS Catalog
Common variants at 10 genomic loci influence hemoglobin A₁(C) levels via glycemic and nonglycemic pathways.
EBI GWAS Catalog
Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA).
EBI GWAS Catalog
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.
EBI GWAS Catalog
Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.
EBI GWAS Catalog
Genome-wide association study identifies common loci influencing circulating glycated hemoglobin (HbA1c) levels in non-diabetic subjects: the Long Life Family Study (LLFS).
EBI GWAS Catalog
Genome-wide association study identifies multiple loci influencing human serum metabolite levels.
EBI GWAS Catalog
Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits.
EBI GWAS Catalog
Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies.
EBI GWAS Catalog
Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians.
EBI GWAS Catalog
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.
EBI GWAS Catalog
Novel association of HK1 with glycated hemoglobin in a non-diabetic population: a genome-wide evaluation of 14,618 participants in the Women's Genome Health Study.
EBI GWAS Catalog
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.
EBI GWAS Catalog
Variants in MTNR1B influence fasting glucose levels.
EBI GWAS Catalog
Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels.
EBI GWAS Catalog

Variation

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See Variation Viewer (GRCh37.p13)

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

  • MGC141936

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables glucose-6-phosphatase activity EXP
Inferred from Experiment
more info
 PubMed 
enables glucose-6-phosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in gluconeogenesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in gluconeogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in gluconeogenesis TAS
Traceable Author Statement
more info
  
involved_in glucose 6-phosphate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in glucose homeostasis IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of insulin secretion IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
is_active_in membrane IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
glucose-6-phosphatase 2
Names
G-6-Pase 2
G6Pase 2
glucose-6-phosphatase, catalytic, 2
islet-specific G6CP-related protein
islet-specific glucose-6-phosphatase catalytic subunit-related protein
islet-specific glucose-6-phosphatase-related protein
NP_001075155.1
NP_066999.1
XP_011509866.1
XP_011509867.1
XP_054185460.1
XP_054185461.1
XP_054199213.1
XP_054199214.1

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_011682.1 RefSeqGene

    Range
    5052..13761
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001081686.2 → NP_001075155.1  glucose-6-phosphatase 2 isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an exon in the coding region, which results in a frameshift and an early stop codon, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1.
    Source sequence(s)
    AC069137, BC104778, BQ268961, CA865646, CR627438
    Consensus CDS
    CCDS46443.1
    UniProtKB/Swiss-Prot
    Q9NQR9
    Related
    ENSP00000396939.2, ENST00000429379.2
    Conserved Domains (1) summary
    cl00474
    Location:38 → 140
    PAP2_like; PAP2_like proteins, a super-family of histidine phosphatases and vanadium haloperoxidases, includes type 2 phosphatidic acid phosphatase or lipid phosphate phosphatase (LPP), Glucose-6-phosphatase, Phosphatidylglycerophosphatase B and bacterial acid ...

  2. NM_021176.3 → NP_066999.1  glucose-6-phosphatase 2 isoform 1

    See identical proteins and their annotated locations for NP_066999.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC069137, BC104778, CA865646, CR627438
    Consensus CDS
    CCDS2230.1
    UniProtKB/Swiss-Prot
    E9PAX2, Q6AHZ0, Q9NQR9
    Related
    ENSP00000364512.3, ENST00000375363.8
    Conserved Domains (1) summary
    cd03381
    Location:38 → 278
    PAP2_glucose_6_phosphatase; PAP2_like proteins, glucose-6-phosphatase subfamily. Glucose-6-phosphatase converts glucose-6-phosphate into free glucose and is active in the lumen of the endoplasmic reticulum, where it is bound to the membrane. The generation of free glucose is an ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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
    168901291..168910000
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011511564.4 → XP_011509866.1  glucose-6-phosphatase 2 isoform X2

    See identical proteins and their annotated locations for XP_011509866.1

    Conserved Domains (1) summary
    cl00474
    Location:38 → 202
    PAP2_like; PAP2_like proteins, a super-family of histidine phosphatases and vanadium haloperoxidases, includes type 2 phosphatidic acid phosphatase or lipid phosphate phosphatase (LPP), Glucose-6-phosphatase, Phosphatidylglycerophosphatase B and bacterial acid ...

  2. XM_011511565.4 → XP_011509867.1  glucose-6-phosphatase 2 isoform X1

    See identical proteins and their annotated locations for XP_011509867.1

    Conserved Domains (1) summary
    cl00474
    Location:1 → 162
    PAP2_like; PAP2_like proteins, a super-family of histidine phosphatases and vanadium haloperoxidases, includes type 2 phosphatidic acid phosphatase or lipid phosphate phosphatase (LPP), Glucose-6-phosphatase, Phosphatidylglycerophosphatase B and bacterial acid ...

Reference GRCh38.p14 ALT_REF_LOCI_1

Genomic

  1. NW_003315909.1 Reference GRCh38.p14 ALT_REF_LOCI_1

    Range
    87918..96627
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054329486.1 → XP_054185461.1  glucose-6-phosphatase 2 isoform X2

  2. XM_054329485.1 → XP_054185460.1  glucose-6-phosphatase 2 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    169375781..169384490
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054343239.1 → XP_054199214.1  glucose-6-phosphatase 2 isoform X2

  2. XM_054343238.1 → XP_054199213.1  glucose-6-phosphatase 2 isoform X1

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9NQR9.1 GenPept UniProtKB/Swiss-Prot:Q9NQR9

Gene LinkOut

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