GCK glucokinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: GCKprovided by HGNC
Official Full Name: glucokinaseprovided by HGNC
Primary source: HGNC:HGNC:4195
See related: Ensembl:ENSG00000106633 MIM:138079; AllianceGenome:HGNC:4195
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: GK; GLK; HK4; HHF3; HKIV; HXKP; LGLK; MODY2; PNDM1; FGQTL3
Summary: This gene encodes a member of the hexokinase family of proteins. Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. In contrast to other forms of hexokinase, this enzyme is not inhibited by its product glucose-6-phosphate but remains active while glucose is abundant. The use of multiple promoters and alternative splicing of this gene result in distinct protein isoforms that exhibit tissue-specific expression in the pancreas and liver. In the pancreas, this enzyme plays a role in glucose-stimulated insulin secretion, while in the liver, this enzyme is important in glucose uptake and conversion to glycogen. Mutations in this gene that alter enzyme activity have been associated with multiple types of diabetes and hyperinsulinemic hypoglycemia. [provided by RefSeq, Aug 2017]
Expression: Low expression observed in reference dataset See more
Orthologs: mouse all
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Genomic context

Location:: 7p13

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (44143213..44189439, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (44301768..44348026, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (44182812..44229038, complement)

Chromosome 7 - NC_000007.14 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

G-quadruplex forming regions in GCK and TM6SF2 are targets for differential DNA methylation in metabolic disease and hepatocellular carcinoma patients.
Title: G-quadruplex forming regions in GCK and TM6SF2 are targets for differential DNA methylation in metabolic disease and hepatocellular carcinoma patients.
Characterizing glucokinase variant mechanisms using a multiplexed abundance assay.
Title: Characterizing glucokinase variant mechanisms using a multiplexed abundance assay.
Two novel GCK mutations in Chinese patients with maturity-onset diabetes of the young.
Title: Two novel GCK mutations in Chinese patients with maturity-onset diabetes of the young.
An Italian MODY family with proband and son carrying variants in GCK and HFN1A: is it a true case of digenic MODY?
Title: An Italian MODY family with proband and son carrying variants in GCK and HFN1A: is it a true case of digenic MODY?
Glucokinase Variant Proteins Are Resistant to Fasting-Induced Uridine Diphosphate Glucose-Dependent Degradation in Maturity-Onset Diabetes of the Young Type 2 Patients.
Title: Glucokinase Variant Proteins Are Resistant to Fasting-Induced Uridine Diphosphate Glucose-Dependent Degradation in Maturity-Onset Diabetes of the Young Type 2 Patients.
Maternal and Infant Outcomes in GCK-MODY Complicated by Pregnancy.
Title: Maternal and Infant Outcomes in GCK-MODY Complicated by Pregnancy.
A comprehensive map of human glucokinase variant activity.
Title: A comprehensive map of human glucokinase variant activity.
BMAL1 Regulates Glucokinase Expression Through E-Box Elements In Vitro.
Title: BMAL1 Regulates Glucokinase Expression Through E-Box Elements In Vitro.
Glucokinase Inactivation Ameliorates Lipid Accumulation and Exerts Favorable Effects on Lipid Metabolism in Hepatocytes.
Title: Glucokinase Inactivation Ameliorates Lipid Accumulation and Exerts Favorable Effects on Lipid Metabolism in Hepatocytes.
Diagnosis, treatment and genetic analysis of two cases of congenital hyperinsulinemic hypoglycemia caused by GCK gene mutation.
Title: Diagnosis, treatment and genetic analysis of two cases of congenital hyperinsulinemic hypoglycemia caused by GCK gene mutation.

Submit: New GeneRIF Correction See all GeneRIFs (258)

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

Associated conditions

Description	Tests
Hyperinsulinism due to glucokinase deficiency MedGen: C1865290 OMIM: 602485 GeneReviews: Nonsyndromic Genetic Hyperinsulinism Overview	Compare labs
Maturity-onset diabetes of the young type 2 MedGen: C0342277 OMIM: 125851 GeneReviews: Maturity-Onset Diabetes of the Young Overview	Compare labs
Permanent neonatal diabetes mellitus MedGen: C1833104 GeneReviews: Permanent Neonatal Diabetes Mellitus	Compare labs
Permanent neonatal diabetes mellitus 1 MedGen: C5393570 OMIM: 606176 GeneReviews: Permanent Neonatal Diabetes Mellitus	Compare labs
Type 2 diabetes mellitus MedGen: C0011860 OMIM: 125853 GeneReviews: WFS1 Spectrum Disorder	Compare labs

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 study assessing the association of glycated hemoglobin A1C (HbA1C) associated variants with HbA1C, chronic kidney disease and diabetic retinopathy in populations of Asian ancestry. 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
Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians. 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
Large-scale genome-wide association studies in East Asians identify new genetic loci influencing metabolic traits. 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
New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the Korean population. 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
Variants in MTNR1B influence 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)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of glucokinase (hexokinase 4) (GCK) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with GCK	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

GDB:191176 (e-PCR)
- UniSTS:155648

RH11460 (e-PCR)
- UniSTS:29022

SHGC-12738 (e-PCR)
- UniSTS:49837

GDB:3754299 (e-PCR)
- UniSTS:30160

GDB:1317412 (e-PCR)
- UniSTS:25306

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables D-glucose binding	IDA Inferred from Direct Assay more info	PubMed
enables fructokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glucokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables glucokinase activity	IDA Inferred from Direct Assay more info	PubMed
enables glucokinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables glucokinase activity	TAS Traceable Author Statement more info
enables glucose sensor activity	ISS Inferred from Sequence or Structural Similarity more info
enables mannokinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in NADP metabolic process	IEA Inferred from Electronic Annotation more info
involved_in calcium ion import	IEA Inferred from Electronic Annotation more info
involved_in canonical glycolysis	TAS Traceable Author Statement more info
involved_in carbohydrate phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in cellular response to leptin stimulus	ISS Inferred from Sequence or Structural Similarity more info
involved_in glucose 6-phosphate metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glucose 6-phosphate metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glucose catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glucose homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in glucose metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycolytic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in intracellular glucose homeostasis	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of gluconeogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of glycogen biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of glycolytic process	NAS Non-traceable Author Statement more info	PubMed
involved_in regulation of insulin secretion	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of insulin secretion	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of potassium ion transport	IEA Inferred from Electronic Annotation more info
involved_in response to glucose	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
is_active_in cytosol	IBA Inferred from Biological aspect of Ancestor more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleoplasm	TAS Traceable Author Statement more info

General protein information

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Preferred Names: hexokinase-4

Names: ATP:D-hexose 6-phosphotransferase; HK IV; glucokinase (hexokinase 4); hexokinase D, pancreatic isozyme; hexokinase type IV

NP_000153.1

EC 2.7.1.1

NP_001341729.1

EC 2.7.1.1

NP_001341730.1

EC 2.7.1.1

NP_001341731.1

EC 2.7.1.1

NP_001341732.1

EC 2.7.1.1

NP_277042.1

EC 2.7.1.1

NP_277043.1

EC 2.7.1.1

XP_024302475.1

EC 2.7.1.1

XP_054213840.1

EC 2.7.1.1

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

NG_008847.2 RefSeqGene

Range

13732..58896

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_1074

mRNA and Protein(s)

NM_000162.5 → NP_000153.1 hexokinase-4 isoform 1

See identical proteins and their annotated locations for NP_000153.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the isoform expressed specifically in pancreatic islet beta cells. Its first exon is specific to this variant, which has a unique 5' UTR. Isoform 1 has a distinct N-terminus; the remainder of the protein is identical to isoforms 2 and 3.

Source sequence(s)

AC006454, BC001890

Consensus CDS

CCDS5479.1

UniProtKB/Swiss-Prot

A4D2J2, A4D2J3, P35557, Q05810

UniProtKB/TrEMBL

A7LFL1, Q53Y25

Related

ENSP00000384247.3, ENST00000403799.8

Conserved Domains (2) summary

COG5026
Location:8 → 458

COG5026; Hexokinase [Carbohydrate transport and metabolism]

pfam00349
Location:15 → 215

Hexokinase_1
NM_001354800.1 → NP_001341729.1 hexokinase-4 isoform 4

Status: REVIEWED

Source sequence(s)

AC006454

Consensus CDS

CCDS94092.1

UniProtKB/TrEMBL

A0A5F9ZGW4, A7LFL1

Related

ENSP00000499852.1, ENST00000673284.1

Conserved Domains (2) summary

COG5026
Location:8 → 456

COG5026; Hexokinase [Carbohydrate transport and metabolism]

pfam00349
Location:15 → 215

Hexokinase_1
NM_001354801.1 → NP_001341730.1 hexokinase-4 isoform 7

Status: REVIEWED

Source sequence(s)

AC006454, M90299

Related

ENST00000683378.1

Conserved Domains (1) summary

pfam03727
Location:2 → 118

Hexokinase_2
NM_001354802.1 → NP_001341731.1 hexokinase-4 isoform 5

Status: REVIEWED

Source sequence(s)

AC006454

Conserved Domains (1) summary

pfam03727
Location:1 → 75

Hexokinase_2
NM_001354803.2 → NP_001341732.1 hexokinase-4 isoform 6

Status: REVIEWED

Source sequence(s)

AC006454, M90299

Consensus CDS

CCDS94091.1

UniProtKB/TrEMBL

H7BXV0

Related

ENSP00000338009.5, ENST00000336642.9

Conserved Domains (1) summary

pfam03727
Location:19 → 133

Hexokinase_2
NM_033507.3 → NP_277042.1 hexokinase-4 isoform 2

See identical proteins and their annotated locations for NP_277042.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) encodes the major isoform expressed in liver. Its first exon is specific to the liver transcripts, variants 2 and 3, but it lacks a second liver-specific exon found in variant 3. Isoform 2 has a distinct N-terminus; the remainder of the protein is identical to isoforms 1 and 3.

Source sequence(s)

AK122876, CD251038, M69051, M90299

Consensus CDS

CCDS5480.1

UniProtKB/TrEMBL

A7LFL1

Related

ENSP00000223366.2, ENST00000345378.7

Conserved Domains (2) summary

COG5026
Location:17 → 459

COG5026; Hexokinase [Carbohydrate transport and metabolism]

pfam00349
Location:17 → 216

Hexokinase_1
NM_033508.3 → NP_277043.1 hexokinase-4 isoform 3

See identical proteins and their annotated locations for NP_277043.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) is the minor form expressed in liver. Its first exon is specific to the liver transcripts, variants 2 and 3; its second exon is unique to this transcript. Isoform 3 has a distinct N-terminus; the remainder of the protein is identical to isoforms 1 and 2.

Source sequence(s)

AK122876, CD251038, DA640823, M69051, M90299

UniProtKB/TrEMBL

A7LFL1

Conserved Domains (2) summary

COG5026
Location:13 → 457

COG5026; Hexokinase [Carbohydrate transport and metabolism]

pfam00349
Location:14 → 214

Hexokinase_1