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

Summary

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

Location:: 2q31.1

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (168901291..168910000)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (169375781..169384490)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (169757801..169766510)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.
Title: G6PC1 and G6PC2 influence G6P flux but not HSD11B1 activity.
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.
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.
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.
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.
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).
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.
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.
The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance, whereas variants in GCK and G6PC2 that increase fasting glucose levels decrease between-subject variance.
Title: Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability.

Submit: New GeneRIF Correction See all GeneRIFs (50)

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 EBI GWAS CatalogPubMed
A polymorphism within the G6PC2 gene is associated with fasting plasma glucose levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants at 10 genomic loci influence hemoglobin A&#x000e2;&#x00082;&#x00081;(C) levels via glycemic and nonglycemic pathways. EBI GWAS Catalog EBI GWAS CatalogPubMed
Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA). EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Identification of HKDC1 and BACE2 as genes influencing glycemic traits during pregnancy through genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed
Multiple nonglycemic genomic loci are newly associated with blood level of glycated hemoglobin in East Asians. EBI GWAS Catalog EBI GWAS CatalogPubMed
New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. EBI GWAS Catalog EBI GWAS CatalogPubMed
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 EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variants in MTNR1B influence fasting glucose levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

General gene information

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Markers

NoName (e-PCR)
- UniSTS:483350

D2S1914 (e-PCR)
- UniSTS:153640

NoName (e-PCR)
- UniSTS:481178

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

EC 3.1.3.9

NP_066999.1

EC 3.1.3.9

XP_011509866.1

EC 3.1.3.9

XP_011509867.1

EC 3.1.3.9

XP_054185460.1

EC 3.1.3.9

XP_054185461.1

EC 3.1.3.9

XP_054199213.1

EC 3.1.3.9

XP_054199214.1

EC 3.1.3.9

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

NG_011682.1 RefSeqGene

Range

5052..13761

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

168901291..168910000

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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 ...