GCK - glucokinase Gene

Also Known as GK; GLK; HK4; HHF3; HKIV; HXKP; LGLK; MODY2; PNDM1; FGQTL3

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 2645

About GCK

Cytogenetic location: 7p13 Genomic coordinates (GRCh38): 7:44,143,213-44,189,439 (from NCBI)

This gene has 14 transcripts (splice variants), 214 orthologues, 4 paralogues and is associated with 7 phenotypes. Low expression observed in reference dataset.

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]

GCK Products (8)

mRNA	Protein	Name
NM_033507.3	NP_277042.1	hexokinase-4 isoform 2
NM_001354801.1	NP_001341730.1	hexokinase-4 isoform 7
NM_000162.5	NP_000153.1	hexokinase-4 isoform 1
NM_001354803.2	NP_001341732.1	hexokinase-4 isoform 6
NM_001354800.1	NP_001341729.1	hexokinase-4 isoform 4
XM_024446707.2	XP_024302475.1	hexokinase-4 isoform X1
NM_033508.3	NP_277043.1	hexokinase-4 isoform 3
NM_001354802.1	NP_001341731.1	hexokinase-4 isoform 5

Gene Ontology

Molecular Function
Biological Process

Molecular Function GO Annotation	Evidence	References	Source
enables ATP binding	IDA IDA: Inferred from direct assay	8446612	GOA
enables D-glucose binding	IDA IDA: Inferred from direct assay	8446612	GOA
enables glucokinase activity	IDA IDA: Inferred from direct assay	8446612	GOA
enables glucokinase activity	IMP IMP: Inferred from mutant phenotype	18322640	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	11522786	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in glucose 6-phosphate metabolic process	IMP IMP: Inferred from mutant phenotype	18322640	GOA
involved in glucose catabolic process	IMP IMP: Inferred from mutant phenotype	12941786	GOA
involved in glucose homeostasis	IMP IMP: Inferred from mutant phenotype	8132752	GOA
involved in negative regulation of gluconeogenesis	IMP IMP: Inferred from mutant phenotype	8878425	GOA
involved in positive regulation of glycogen biosynthetic process	IMP IMP: Inferred from mutant phenotype	8878425	GOA
involved in positive regulation of insulin secretion	IMP IMP: Inferred from mutant phenotype	8132752	GOA
involved in regulation of insulin secretion	IMP IMP: Inferred from mutant phenotype	20668700	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

GCK Protein Structure

Hexokinase_1

Hexokinase_2

0
100
200
300
400
465 a.a.

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

GCK Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	GCK	P35557	SPDYE4	Homo sapiens	A6NLX3	Y2H Array	32296183
Intra	GCK	P35557	SPDYE4	Homo sapiens	A6NLX3	Y2H Prey Pooling	32296183
Intra	GCK	P35557	PFKFB1	Homo sapiens	P16118	Phage Display	11522786
Intra	GCK	P35557	GCKR	Homo sapiens	Q14397	Validated Y2H	32296183
Intra	GCK	P35557	GCKR	Homo sapiens	Q14397	Y2H Prey Pooling	32296183
Intra	GCK	P35557	GCKR	Homo sapiens	Q14397	Y2H Array	32296183

Cross: Cross-species interaction Intra: Intraspecies interaction

Recombinant GCK Proteins

Cat. No.	Product Name	Accession	Purity
HY-P75790	Glucokinase/GCK Protein, Human	P35557-1/NP_000153.1 (L2-Q465)	≥ 95%, as determined by reducing SDS-PAGE.

GCK Antibodies

Cat. No.	Product Name	Application	Reactivity
HY-P82295	Glucokinase Antibody (YA2040)	WB	Human
HY-P85184	Glucokinase Antibody (YA4876)	WB, ELISA	Human

Related Diseases

Diseases	Alias
Renal Cysts And Diabetes Syndrome	RCAD Mody5 Congenital Anomalies Of The Kidney And Urinary Tract With Diabetes Cakut With Diabetes Maturity-Onset Diabetes Of The Young Type 5 Tubulointerstitial Kidney Disease, Autosomal Dominant, 3 Adtkd3 Atypical Familial Juvenile Hyperuricemic Nephropathy Atypical Fjhn Familial Hypoplastic Glomerulocystic Kidney Maturity-Onset Diabetes Of The Young, Type 5 Hyperuricemic Nephropathy, Familial Juvenile, Atypical Fjhn, Atypical Glomerulocystic Kidney Disease, Hypoplastic Type Glomerulocystic Kidney, Familial Hypoplastic Hypoplastic Type Glomerulocystic Kidney Disease Glomerulocystic Kidney Disease Hypoplastic Type Renal-Diabetes Mody5 Syndrome
Maturity-Onset Diabetes Of The Young, Type 11	Maturity-Onset Diabetes Of The Young Type 11 MODY11 Maturity-Onset Diabetes Of The Young 11 Mody-11 Mody Type 11 Diabetes Of The Young, Maturity-Onset, Type 11
Hyperinsulinemic Hypoglycemia	Nesidioblastosis Islet Cell Hyperplasia Persistent Hyperinsulinemia Hypoglycemia Of Infancy Hyperinsulinemic Hypoglycaemia
Factitious Disorder	Munchausen Syndrome Factitious Disorders Münchausen Syndrome
Wolfram Syndrome	Didmoad Syndrome Didmoad Diabetes Insipidus And Mellitus With Optic Atrophy And Deafness Wfs Diabetes Insipidus, Diabetes Mellitus, Optic Atrophy, And Deafness Didmoadud Diabetes Insipidus-Diabetes Mellitus-Optic Atrophy-Deafness Syndrome Diabetes Insipidus-Diabetes Mellitus-Optic Atrophy-Hearing Loss Syndrome
Maturity-Onset Diabetes Of The Young, Type 9	Maturity-Onset Diabetes Of The Young Type 9 MODY9 Maturity-Onset Diabetes Of The Young, Type Ix Maturity-Onset Diabetes Of The Young 9 Mody-9 Mody Type 9 Diabetes Of The Young, Maturity-Onset, Type 9
Abdominal Obesity-Metabolic Syndrome 1	Metabolic Syndrome X Metabolic Syndrome AOMS1 Dysmetabolic Syndrome X Metabolic Disease Abdominal Obesity Metabolic Syndrome
Munchausen By Proxy	Munchausen Syndrome By Proxy Munchausen By Proxy Syndrome Münchausen Syndrome By Proxy
Sudden Infant Death Syndrome	SIDS Sudden Infant Death Syndrome, Susceptibility To Cot Death Crib Death Sudden Death Of Nonspecific Cause In Infancy Sudden Infant Death Death, Sudden, Syndrome, Infant
Type 2 Diabetes Mellitus	Insulin Resistance NIDDM Diabetes Mellitus, Non-Insulin-Dependent Type 2 Diabetes T2D Noninsulin-Dependent Diabetes Mellitus Diabetes Mellitus, Type Ii Maturity-Onset Diabetes Insulin Resistance, Severe, Digenic Diabetes Mellitus, Type 2 Diabetes Mellitus, Noninsulin-Dependent Diabetes Mellitus, Noninsulin-Dependent, Association With Diabetes Mellitus, Noninsulin-Dependent, Late Onset Hypertension, Insulin Resistance-Related, Susceptibility To Insulin Resistance, Susceptibility To Non-Insulin-Dependent Diabetes Mellitus Type Ii Diabetes Mellitus Adult-Onset Diabetes Mellitus Maturity-Onset Diabetes Mellitus Diabetes Mellitus Type 2 Type Ii Diabetes Type 2 Diabetes Mellitus, Susceptibility To Diabetes, Type 2 Diabetes Mellitus, Noninsulin-Dependent, Susceptibility To Diabetes Mellitus, Non-Insulin-Dependent, Susceptibility To Diabetes Mellitus, Type 2, Susceptibility To Diabetes Mellitus, Noninsulin-Dependent, 2 Diabetes Mellitus, Type Ii, Susceptibility To Hypertension, Insulin Resistance-Related Adult-Onset Diabetes Aodm Diabetes Mellitus, Adult-Onset Diabetes Mellitus Type Ii Diabetes Mellitus Type 2, Susceptibility To Diabetes, Type Ii, Susceptibility To Diabetes Type 2 Diabetes Mellitus Adult Onset Diabetes Maturity Onset Diabetes Nonketotic Diabetes Non-Insulin Dependent Diabetes Mellitus T2dm - [Type 2 Diabetes Mellitus] Niddm - [Non Insulin Dependent Diabetes Mellitus] Dm2 Dm Type Ii Diabetic Type 2 Insulin Requiring Type 2 Diabetes Noninsulin Dependent Diabetes Non-Insulin-Dependent Diabetes Mellitus Without Complications Diabetes Due To Insulin Secretory Defect Diabetes Mellitus Due To Insulin Secretory Defect Non-Insulin-Dependent Diabetes Of The Young Senile Diabetes Nonketotic Hyperglycaemia Stable Diabetes
Monogenic Diabetes
Neonatal Diabetes	Neonatal Diabetes Mellitus Diabetes Mellitus Syndrome In Newborn Infant Ndm
Familial Hyperlipidemia	Familial Hyperlipoproteinemia Hyperlipidaemia Hyperlipoproteinemias Hyperlipemia Hyperlipidemias Hyperlipidemia
Hyperinsulinemic Hypoglycemia, Familial, 6	Hyperinsulinism-Hyperammonemia Syndrome HHF6 Familial Hyperinsulinemic Hypoglycemia 6 Hi/Ha Syndrome Ha/Hi Syndrome Hyperinsulinemic Hypoglycemia Familial 6 Hyperinsulinism Hyperammonemia Syndrome Hhs
Hyperinsulinemic Hypoglycemia, Familial, 3	HHF3 Hyperinsulinism Due To Glucokinase Deficiency Familial Hyperinsulinemic Hypoglycemia 3 Hyperinsulinemic Hypoglycemia Due To Glucokinase Deficiency Hyperinsulinemic Hypoglycemia Familial 3 Congenital Hyperinsulinism Persistent Hyperinsulinemic Hypoglycemia Of Infancy Phhi Hypoglycemia, Hyperinsulinemic, Familial, Type 3
Glucose Intolerance	Glucose: Intolerance Glucose: Malabsorption Malabsorption Of Glucose Impaired Glucose Tolerance
Hyperinsulinism	Hyperinsulinemia
Maturity-Onset Diabetes Of The Young, Type 7	Maturity-Onset Diabetes Of The Young Type 7 MODY7 Maturity-Onset Diabetes Of The Young, Type Vii Maturity-Onset Diabetes Of The Young 7 Mody-7 Mody Type 7 Diabetes Of The Young, Maturity-Onset, Type 7
Pancreatic Agenesis	Partial Pancreatic Agenesis Congenital Pancreatic Agenesis Partial Agenesis Of The Pancreas Agenesis, Pancreatic Pancreatic Agenesis, Congenital
Pancreatic Cystadenoma	Cystadenoma Of Pancreas
Hyperinsulinemic Hypoglycemia, Familial, 7	HHF7 Exercise-Induced Hyperinsulinemic Hypoglycemia Exercise-Induced Hyperinsulinism Familial Hyperinsulinemic Hypoglycemia 7 Eihi Hyperinsulinism Due To Monocarboxylate Transporter 1 Deficiency Hyperinsulinism Due To Slc16a1 Deficiency Hyperinsulinemic Hypoglycemia, Exercise-Induced Exercise Induced Hyperinsulinemic Hypoglycemia Hyperinsulinemic Hypoglycemia Exercise-Induced Hyperinsulinemic Hypoglycemia Familial 7
Maturity-Onset Diabetes Of The Young, Type 1	Maturity-Onset Diabetes Of The Young Type 1 MODY1 Mild Juvenile Diabetes Mellitus Mody, Type I Diabetes Mellitus Type 2 Mody Type 1 Mody, Type 1 Maturity-Onset Diabetes Of The Young 1 Mody-1 Diabetes Of The Young, Maturity-Onset, Type 1
Maturity-Onset Diabetes Of The Young, Type 2	Maturity-Onset Diabetes Of The Young Type 2 MODY2 Mody Glucokinase-Related Mody Type 2 Mody, Type 2 Mody, Glucokinase-Related Mody, Type Ii Maturity-Onset Diabetes Of The Young 2 Mody-2 Diabetes Of The Young, Maturity-Onset, Type 2 Diabetes Mellitus Autosomal Dominant Type Ii
Permanent Neonatal Diabetes Mellitus	Pndm Permanent Diabetes Mellitus Of Infancy Pdmi Neonatal Diabetes Mellitus, Permanent
Body Mass Index Quantitative Trait Locus 11	OBESITY Obesity, Susceptibility To Leanness, Inherited Obesity, Susceptibility To, Bmiq11 Obesity, Mild, Early-Onset Obesity, Association With Obesity, Early-Onset, Susceptibility To Obesity, Severe Obesity, Severe, And Type Ii Diabetes Obesity, Late-Onset BMIQ11 Obesity Bmiq11 Obesity, Early-Onset Obesity , Susceptibility To Simple Obesity Nos Excess Fat Obesity, Not Elsewhere Classified, Body Mass Index Not Elsewhere Classified Adiposis
Contractures, Pterygia, And Spondylocarpotarsal Fusion Syndrome 1a	Multiple Pterygium Syndrome, Autosomal Dominant CPSFS1A Contractures, Pterygia, And Spondylocarpostarsal Fusion Syndrome 1a Autosomal Dominant Disease Contractures, Pterygia, And Variable Skeletal Fusions Syndrome 1a Cpskf1a Pterygium Syndrome, Multiple Autosomal Dominant Arthrogryposis, Distal, Type 8, Formerly Da8, Formerly Autosomal Dominant Multiple Pterygium Syndrome Distal Arthrogryposis Type 8 Arthrogryposis, Distal, Type 8 Da8 Pterygium Syndrome, Multiple, Autosomal Dominant Autosomal Dominant Disorder
Maturity-Onset Diabetes Of The Young, Type 8, With Exocrine Dysfunction	Maturity-Onset Diabetes Of The Young Type 8 MODY8 Dped Maturity-Onset Diabetes Of The Young, Type Viii Mody Type 8 Diabetes And Pancreatic Exocrine Dysfunction Diabetes-Pancreatic Exocrine Dysfunction Syndrome Diabetes And Pancreatic Exocrine Maturity-Onset Diabetes Of The Young Type 8 With Exocrine Dysfunction Maturity-Onset Diabetes Of The Young 8 With Exocrine Dysfunction Diabetes And Pancreatic Exocrine Dysfunction Syndrome Mody-8 Diabetes Of The Young, Maturity-Onset, Type 8
Donohue Syndrome	Leprechaunism Leprechaunism Syndrome Donohue'S Syndrome LEPRCH
Intestinal Atresia
Diabetes Mellitus	Diabetes
Maturity-Onset Diabetes Of The Young, Type 6	MODY6 Maturity-Onset Diabetes Of The Young Type 6 Maturity-Onset Diabetes Of The Young 6 Mody Type 6 Mody, Type 6 Mody-6 Diabetes Of The Young, Maturity-Onset, Type 6
Maturity-Onset Diabetes Of The Young, Type 13	Maturity-Onset Diabetes Of The Young Type 13 MODY13 Mody Type 13 Mody, Type 13 Maturity-Onset Diabetes Of The Young 13 Diabetes Of The Young, Maturity-Onset, Type 13
Transient Neonatal Diabetes Mellitus	Diabetes Mellitus, Transient Neonatal Tndm Chromosome 6-Associated Transient Diabetes Mellitus Dmtn Diabetes Mellitus, 6q24-Related Transient Neonatal Tndm1 Neonatal Diabetes Mellitus, Transient Tndm -[Transient Neonatal Diabetes Mellitus]
Maturity-Onset Diabetes Of The Young	MODY Maturity Onset Diabetes Mellitus In Young Mason-Type Diabetes Mason Type Diabetes Maturity Onset Diabetes Of The Young Mody Syndrome Diabetes Of The Young, Maturity-Onset
Maturity-Onset Diabetes Of The Young, Type 10	Maturity-Onset Diabetes Of The Young Type 10 MODY10 Maturity-Onset Diabetes Of The Young 10 Mody-10 Mody Type 10 Diabetes Of The Young, Maturity-Onset, Type 10
Insulinoma	Islet Cell Adenoma Insulin-Producing Tumor Of Islet Cells Adenoma Islet Cell Islet Cell Tumor Experimental Organism Islet Cell Adenoma Neoplasm
Diabetes Mellitus, Permanent Neonatal, 1	PNDM1 Pdmi Dend Syndrome Permanent Diabetes Mellitus Of Infancy Permanent Neonatal Diabetes Mellitus 1 Diabetes Mellitus, Permanent, Of Infancy Diabetes Mellitus, Permanent Neonatal 1 Developmental Delay-Epilepsy-Neonatal Diabetes Syndrome Dend Developmental Delay Epilepsy And Neonatal Diabetes Diabetes Mellitus Permanent Neonatal With Neurologic Features Diabetes Mellitus, Permanent Neonatal, Type 1
Prediabetes Syndrome	Impaired Glucose Tolerance Prediabetes Prediabetic State IGT Igt - [Impaired Glucose Tolerance] Impaired Glucose Tolerance With Unspecified Complication Impaired Glucose Tolerance Without Complication Abnormal Glucose Tolerance
Type 1 Diabetes Mellitus	Diabetes Mellitus, Insulin-Dependent Diabetes Mellitus Type 1 IDDM Insulin-Dependent Diabetes Mellitus Type 1 Diabetes T1D Juvenile-Onset Diabetes Jod Diabetes Mellitus, Type 1 Diabetes Mellitus, Insulin-Dependent-1 Type I Diabetes Mellitus Autoimmune Diabetes Juvenile Diabetes Juvenile-Onset Diabetes Mellitus Diabetes, Insulin Dependent Insulin-Dependent Diabetes Mellitus-1 Diabetes Mellitus Insulin-Dependent Diabetes Autoimmune Diabetes Mellitus, Insulin-Dependent, Susceptibility To Diabetes Mellitus, Type 1, Susceptibility To Diabetes Type 1 Type I Diabetes Diabetes, Autoimmune T1dm - [Type 1 Diabetes Mellitus] Iddm - [Insulin Dependent Diabetes Mellitus] Type 1 Iddm Juvenile Diabetes Mellitus Without Compications Idiopathic Insulin-Dependent Diabetes Mellitus Without Complications Juvenile-Onset Diabetes Mellitus Without Compications Ketosis-Prone Diabetes Mellitus Without Compications Juvenile-Onset-Type Diabetes Mellitus Without Compications
Hypoglycemia	Hypoglycaemia Low Blood Sugar Hypoglycaemia Nos Spontaneous Hypoglycaemia Nondiabetic Hypoglycaemia Hypoglycaemic Disorder Nos Hypoglycaemic Syndrome
Fructose-1,6-Bisphosphatase Deficiency	Fructose-1,6-Diphosphatase Deficiency Baker-Winegrad Disease FBP1D Fbpase Deficiency Fructose 1,6 Diphosphatase Deficiency Fructose 1 Phosphate Aldolase Deficiency Fbp1 Deficiency Hereditary Fructose Intolerance Syndrome
Isolated Permanent Neonatal Diabetes Mellitus	Isolated Pndm Monogenic Diabetes Of Infancy
Hyperglycemia
Gestational Diabetes	Gestational Diabetes Mellitus GDM Diabetes Mellitus Arising In Pregnancy Maternal Gestational Diabetes Mellitus Diabetes Mellitus, Gestational Diabetes Mellitus, Pregnancy Related Diabetes, Pregnancy-Induced Diabetes Gestational Diabetes, Gestational Diabetes Of Pregnancy Gdm - [Gestational Diabetes Mellitus] Gestational Diabetes Mellitus Nos Gestational Diabetes Complicating Pregnancy, Childbirth, Or The Puerperium
Maturity-Onset Diabetes Of The Young, Type 4	Maturity-Onset Diabetes Of The Young Type 4 MODY4 Mody, Type Iv Mody Type 4 Mody, Type 4 Maturity-Onset Diabetes Of The Young 4 Mody-4 Diabetes Of The Young, Maturity-Onset, Type 4 Maturity-Onset Diabetes Of The Young, Type Iv
Fructosuria, Essential	Essential Fructosuria Ketohexokinase Deficiency Fructosuria Hepatic Fructokinase Deficiency Fructokinase Deficiency FRUCT Deficiency Of Fructokinase
Maturity-Onset Diabetes Of The Young, Type 3	Maturity-Onset Diabetes Of The Young Type 3 MODY3 Mody, Type Iii Mody Type 3 Mody, Type 3 Maturity-Onset Diabetes Of The Young 3 Mody-3 Diabetes Of The Young, Maturity-Onset, Type 3

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (16)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-147141	HS-276	Inhibitor	98.93%	Unkown
HY-15489	Scriptaid		98.59%	Unkown
HY-10943	GNF-7	Inhibitor	99.70%	Unkown
HY-123714	TL4-12		99.82%	Unkown
HY-137342	SB1-G-187	Degrader	98.70%	Unkown
HY-137343	DB-0646	Degrader	98.0%	Unkown
HY-RS04706	FAM20C Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-147141A	HS-276 hydrochloride	Inhibitor	/	Unkown
HY-147141B	HS-276 formic	Inhibitor	/	Unkown
HY-170365	HPK1-IN-55	Inhibitor	/	Unkown
HY-183809	ZSW	Inhibitor	/	Unkown
HY-RS05329	GCK Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS05330	Gck Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS05331	Gck Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS08074	MAP4K2 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS08075	Map4k2 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Macaca mulatta	GCK	VGNC	VGNC:72901
Mus musculus	GCK	MGD	MGI:1270854
Felis catus	GCK	VGNC	VGNC:62493
Bos taurus	GCK	VGNC	VGNC:29288
Rattus norvegicus	GCK	RGD	RGD:2670
Others	GCK	NCBI