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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

GCK Gene

protein-coding GIFtS: 74
GCID: GC07M044183

glucokinase (hexokinase 4)

(Previous name: maturity onset diabetes of the young 2 )
(Previous symbol: MODY2)

Explore 55 diseases affiliated with
GCK via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Glucokinase (Hexokinase 4)¹ ²		HXKP²
HK4¹ ² ³		LGLK²
MODY2¹ ²		ATP:D-Hexose 6-Phosphotransferase²
Hexokinase Type IV² ³		Glucokinase¹
HK IV² ³		Hexokinase D, Pancreatic Isozyme²
HHF3² ⁵		Hexokinase-4³
Maturity Onset Diabetes Of The Young 2¹		Hexokinase-D³
FGQTL3²		EC 2.7.1.2³
GK²		Hexokinase-4³
GLK²		Hexokinase-D³
HKIV²		EC 2.7.1⁸

External Ids:	HGNC: 4195¹	Entrez Gene: 2645²	Ensembl: ENSG00000106633⁷	OMIM: 138079⁵	UniProtKB: P35557³

Export aliases for GCK gene to outside databases

Previous GC identifers: GC07M043830 GC07M043890 GC07M043924 GC07M043957 GC07M044150 GC07M044070

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for GCK:

Hexokinases phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways.

Alternative splicing of this gene results in three tissue-specific forms of glucokinase, one found in pancreatic islet

beta cells and two found in liver. The protein localizes to the outer membrane of mitochondria. 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. Mutations in this gene have been associated with non-insulin dependent diabetes mellitus (NIDDM),

maturity onset diabetes of the young, type 2 (MODY2) and persistent hyperinsulinemic hypoglycemia of infancy (PHHI).

(provided by RefSeq, Apr 2009)

UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557

Function: Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose

concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role

of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating

insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an

insulin-sensitive determinant of hepatic glucose usage

Gene Wiki entry for GCK (Glucokinase)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000007.13 NC_018918.1 NT_007819.17 NT_079592.2

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the GCK gene promoter:
AP-1 ATF-2 c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 4): GCK promoter sequence

Search SABiosciences Chromatin IP Primers for GCK

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat GCK

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 7p15.3-p15.1 Ensembl cytogenetic band: 7p13 HGNC cytogenetic band: 7p15.3-p15.1

GCK Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
GCK gene location

GeneLoc information about chromosome 7 GeneLoc Exon Structure

GeneLoc location for GC07M044183: view genomic region (about GC identifiers)

Start:	44,183,870 bp from pter	End:	44,237,769 bp from pter
Size:	53,900 bases	Orientation:	minus strand

1 alternative location:

Chr7-,CRA_TCAG 44,223,370-44,268,527

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557 (See protein sequence)

Recommended Name: Glucokinase

Size: 465 amino acids; 52191 Da

Subunit: Monomer

Miscellaneous: In vertebrates there are four major glucose-phosphorylating isoenzymes, designated hexokinase I, II, III

and IV (glucokinase)

6/19 PDB 3D structures from and Proteopedia for GCK (see all 19):

1GLK (3D)

1V4S (3D)

1V4T (3D)

3A0I (3D)

3F9M (3D)

3FGU (3D)

Secondary accessions: A4D2J2 A4D2J3 Q05810

Alternative splicing: 3 isoforms: P35557-1 P35557-2 P35557-3

Explore the universe of human proteins at neXtProt for GCK: NX_P35557

Post-translational modifications:

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P35557

4/8 DME Specific Peptides for GCK (P35557) (see all 8)

EWGAFGD

EGRMCVN

GFTFSFP

NACYMEE

GCK Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (3 alternative transcripts):

NP_000153.1 NP_277042.1 NP_277043.1

ENSEMBL proteins:

ENSP00000338009 ENSP00000384247 ENSP00000379142 ENSP00000223366 ENSP00000402840

Reactome Protein details: P35557
Human Recombinant Protein Products:

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	ProSpec Recombinant Protein for GCK
	Uscn Proteins for GCK

Gene Ontology (GO): 5/10 cellular component terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005625	soluble fraction	--	--
GO:0005634	nucleus	--	--
GO:0005654	nucleoplasm	TAS	--
GO:0005737	cytoplasm	--	--
GO:0005739	mitochondrion	IEA	--

GCK for ontologies About GeneDecksing

GCK Antibody Products:

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Assay Products for GCK:

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	Uscn ELISAs and CLIAs for GCK

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

GCK for domains About GeneDecksing

4 InterPro domains/families:

IPR019807 Hexokinase_CS

IPR001312 Hexokinase

IPR022672 Hexokinase_N

IPR022673 Hexokinase_C

Graphical View of Domain Structure for InterPro Entry P35557

ProtoNet protein and cluster: P35557

1 Blocks protein family: IPB001312 Hexokinase

UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557

Similarity: Belongs to the hexokinase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557

Function: Catalyzes the initial step in utilization of glucose by the beta-cell and liver at physiological glucose

concentration. Glucokinase has a high Km for glucose, and so it is effective only when glucose is abundant. The role

of GCK is to provide G6P for the synthesis of glycogen. Pancreatic glucokinase plays an important role in modulating

insulin secretion. Hepatic glucokinase helps to facilitate the uptake and conversion of glucose by acting as an

insulin-sensitive determinant of hepatic glucose usage

Catalytic activity: ATP + D-glucose = ADP + D-glucose 6-phosphate

Enzyme regulation: The use of alternative promoters apparently enables the type IV hexokinase gene to be regulated by

insulin in the liver and glucose in the beta cell. This may constitute an important feedback loop for maintaining

glucose homeostasis. Subject to allosteric regulation

Genatlas biochemistry entry for GCK:

glucokinase,expressed in liver and islet beta cells of pancreas,glucose specific,primary regulator of

glucose-controlled insulin secretion,catalyzing the first step of glycolysis,energy pathway

Enzyme Numbers (IUBMB): EC 2.7.1.2¹ EC 2.7.1²

miRNA Products:		OriGene 3'-UTR Clone: GCK Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat GCK
		3 QIAGEN miScript miRNA Assays for microRNAs that regulate GCK:
		hsa-miR-4324 hsa-miR-4253 hsa-miR-544b
		SwitchGear 3'UTR luciferase reporter plasmid: GCK 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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Gene Editing
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DNA2.0 Custom Protein Engineering Service for GCK

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
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		GenScript: all cDNA clones in your preferred vector (see all 3): GCK (NM_000162)
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In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for GCK

Gene Ontology (GO): 5/12 molecular function terms (GO ID links to tree view) (see all 12): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000287	magnesium ion binding	IEA	--
GO:0004340	glucokinase activity	IDA	16173921
GO:0004396	hexokinase activity	--	--
GO:0005515	protein binding	IPI	11522786
GO:0005524	ATP binding	IDA	16173921

GCK for ontologies About GeneDecksing

2 GenomeRNAi human phenotypes for GCK:

Decreased p24 protein expressi

Decreased viability with TRAIL

Animal Models:
Mouse knock-outs for GCK: Gck^tm1.2Mgn Gck^tm1Tka Gck^tm1Ts Gck^tm1Efr
7 MGI mutant phenotypes (inferred from 24 alleles) (MGI details for Gck):

endocrine/exocrine gland	growth/size	hematopoietic system	homeostasis/metabolism	liver/biliary system
mortality/aging	renal/urinary system

GCK for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/21 super-pathways (see all 21) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Galactose metabolism

Galactose metabolism	1.00	Glycogen metabolism	0.40
Galactose metabolism	0.95	Glycogen metabolism	0.40
Galactose metabolism	0.47

Glycolysis and gluconeogenesis (short map)

	Glycolysis and gluconeogenesis (short map)	1.00			Glycolysis and Gluconeogenesis	0.60
	Glycolysis and gluconeogenesis (short map)	0.97			Glycolysis / Gluconeogenesis	0.41

Regulation of beta-cell development

	Regulation of beta-cell development	1.00			Regulation of gene expression in beta cells	0.56
	Maturity onset diabetes of the young	0.56

GDP-glucose biosynthesis

	glucose and glucose-1-phosphate degradation	1.00			trehalose degradation II (trehalase)	0.29
	GDP-glucose biosynthesis	1.00

Translocation of Influenza A virus nonstructural protein 1 (NS1A) into the nucleus

	Regulation of Glucokinase by Glucokinase Regulatory Protein	0.75			Hexose transport	0.55
	Glucose transport	0.57

Pathway sources
See GeneCards unified pathways
Show all pathways

3 EMD Millipore Pathways for GCK

	Glycogen metabolism
	Glycolysis and gluconeogenesis (short map)
	Galactose metabolism

1 Downloadable PowerPoint Slide of QIAGEN Pathway Central Maps for GCK

MODY (Maturity-Onset Diabetes of Young)

3 GeneGo (Thomson Reuters) Pathways for GCK

	Galactose metabolism
	Glycogen metabolism
	Glycolysis and gluconeogenesis (short map)

5/9 BioSystems Pathways for GCK (see all 9)

	MAPK signaling pathway
	SIDS Susceptibility Pathways
	Glycolysis and Gluconeogenesis
	GDP-glucose biosynthesis
	UDP-N-acetyl-D-galactosamine biosynthesis II

5/11 Reactome Pathways for GCK (see all 11)

	NEUROD1- and PDX1-dependent synthesis of glucokinase (GCK) protein
	Regulation of Glucokinase by Glucokinase Regulatory Protein
	Developmental Biology
	Metabolism of carbohydrates
	Hexose transport

1 PharmGKB Pathway for GCK

Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

5/9 Kegg Pathways (Kegg details for GCK) (see all 9):

	Glycolysis / Gluconeogenesis
	Galactose metabolism
	Starch and sucrose metabolism
	Amino sugar and nucleotide sugar metabolism
	Butirosin and neomycin biosynthesis

GCK for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for GCK

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/36 Interacting proteins for GCK (P35557^{1, 3} ENSP00000223366⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 36)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
GCKR	Q14397¹^,³, ENSP00000264717⁴	EBI-709928,EBI-709948 I2D: score=4 STRING: ENSP00000264717
PFKFB1	P16118¹^,³, ENSP00000364145⁴	EBI-709928,EBI-709807 I2D: score=1 STRING: ENSP00000364145
GLUD1	P00367³, ENSP00000277865⁴	I2D: score=1 STRING: ENSP00000277865
PFKFB2	O60825³, ENSP00000356047⁴	I2D: score=2 STRING: ENSP00000356047
BAD	Q92934³	I2D: score=1

About this table

Gene Ontology (GO): 5/33 biological process terms (GO ID links to tree view) (see all 33): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001678	cellular glucose homeostasis	IBA	--
GO:0005975	carbohydrate metabolic process	TAS	--
GO:0005978	glycogen biosynthetic process	IEA	--
GO:0006003	fructose 2,6-bisphosphate metabolic process	IEA	--
GO:0006006	glucose metabolic process	--	--

GCK for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

GCK for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for GCK

10/18 HMDB Compounds for GCK (see all 18) About this table

Compound	Synonyms	CAS #	PubMed Ids
ADP	adenosindiphosphorsaeure (see all 8)	58-64-0	--
Adenosine triphosphate	5'-(tetrahydrogen triphosphate) Adenosine (see all 24)	56-65-5	--
Alpha-D-Glucose	Hexopyranose (see all 11)	492-62-6	--
Beta-D-Fructose 6-phosphate	beta-D-Fructose 6-phosphate (see all 2)	--	--
Beta-D-Glucose	b-D-Glucopyranose (see all 8)	492-61-5	--
Beta-D-Glucose 6-phosphate	beta-D-glucose 6-(dihydrogen phosphate) (see all 3)	--	--
D-Glucose	(+)-Glucose (see all 23)	50-99-7	--
D-Mannose	DL-mannose (see all 13)	3458-28-4	--
Glucosamine	2-Amino-2-deoxy-D-glucopyranose (see all 10)	3416-24-8	--
Glucosamine 6-phosphate	2-Amino-2-deoxy-D-glucose 6-phosphate (see all 14)	3616-42-0	--

5 DrugBank Compounds for GCK About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Beta-D-Glucose	--	50-99-7	target	--	17139284 17016423
2-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide	--	--	target	--	10592235
2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE	--	--	target	--	10592235
2-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide	--	--	target	--	10592235
3-[(4-fluorophenyl)sulfanyl]-N-(4-methyl-1,3-thiazol-2-yl)-6-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]pyridine-2-carboxamide	--	--	target	--	10592235

10/85 Novoseek chemical compound relationships for GCK gene (see all 85) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
mannoheptulose	88	31	10677361 (4), 15202024 (2), 7614462 (2), 9762360 (1) (see all 17)
glucose	83.9	1226	1612193 (10), 10677361 (9), 9762360 (7), 12101177 (7) (see all 99)
fructose 1-phosphate	83.3	18	9762360 (3), 9003425 (3), 10677361 (2), 9230355 (1) (see all 10)
glucose 6-phosphate	77	90	16403021 (7), 10455119 (4), 12765941 (3), 9325299 (2) (see all 45)
fructose-6-phosphate	70.7	14	14627435 (2), 10455119 (2), 9230355 (1), 18556336 (1) (see all 9)
glycogen	66.9	148	11600496 (8), 18165236 (6), 8878425 (6), 16403021 (5) (see all 38)
preproinsulin	64.7	9	11319727 (2), 14563207 (2), 15148392 (1)
d-(5-3h)glucose	62.1	1	11739021 (1)
katp	62	13	17380317 (2), 14641012 (1), 15350960 (1), 17179930 (1) (see all 10)
sulfonylurea	61.1	15	10459863 (4), 11289470 (3), 9166666 (1), 15579781 (1) (see all 8)

Search CenterWatch for drugs/clinical trials and news about GCK / HXK4

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
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Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for GCK gene (3 alternative transcripts):

NM_000162.3 NM_033507.1 NM_033508.1

Unigene Cluster for GCK:

Glucokinase (hexokinase 4)

Hs.1270 [show with all ESTs]

Unigene Representative Sequence: BC001890

8 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000459642 ENST00000336642 ENST00000403799(uc003tkl.2) ENST00000395796(uc003tkj.1)

ENST00000345378(uc003tkk.1) ENST00000437084 ENST00000473353 ENST00000476008

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		3 QIAGEN miScript miRNA Assays for microRNAs that regulate GCK:
		hsa-miR-4324 hsa-miR-4253 hsa-miR-544b
		SwitchGear 3'UTR luciferase reporter plasmid: GCK 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for GCK (see all 7) OriGene shRNA RFP: GCK OriGene siRNA: GCK
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat GCK

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		GenScript: all cDNA clones in your preferred vector (see all 3): GCK (NM_000162)
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		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat GCK

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		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat GCK
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat GCK

Additional cDNA sequence:

AK122876.1 BC001890.1 BT007062.1 EU008605.1 M69051.1 M88011.1 M90299.1

6 DOTS entries:

DT.112070 DT.100750248 DT.91675210 DT.100811067 DT.91908034 DT.99993532

24/48 AceView cDNA sequences (see all 48):

NM_033508 CK823298 CR626628 M88011 BM966913 BC001890 F08353 NM_000162

CA405747 CR590130 AK122876 F04579 NM_033507 M90299 BM966889 BQ101045

BM893645 BX441511 BT007062 AW248814 CD251038 BM893662 BX413251 BE799829

GeneLoc Exon Structure

5/7 Alternative Splicing Database (ASD) splice patterns (SP) for GCK (see all 7) About this scheme

ExUns:	1	^	2a	·	2b	^	3	^	4	^	5	^	6	^	7	^	8	^	9	^	10	^	11a	·	11b	·	11c	^	12	^	13a	·	13b	·	13c	·	13d	·	13e	·	13f	^	14
SP1:																							-		-		-
SP2:			-		-		-																-		-		-
SP3:							-																-		-		-
SP4:																											-				-						-		-		-
SP5:																											-

ECgene alternative splicing isoforms for GCK

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

GCK expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: CCCAACCTAA

About this image

GCK expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

Stem Cell Differentiation: 3 LifeMap Cells

Name

Category

Pancreatic-like islets (Derivation of beta c...)

beta-like cells (Derivation of beta c...)

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See GCK Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for GCK

SOURCE GeneReport for Unigene cluster: Hs.1270

UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557

Tissue specificity: Isoform 1 is expressed in pancreas. Isoform 2 and isoform 3 is expressed in liver

SABiosciences Expression via Pathway-Focused PCR Arrays including GCK:

Insulin Signaling Pathway in human mouse rat

Fatty Liver in human mouse rat

Diabetes in human mouse rat

Glucose Metabolism in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for GCK gene from 8/25 species (see all 25) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	GCK¹	glucokinase (hexokinase 4)	85.21(n) 90.17(a)		430370 XM_427930.3 XP_427930.3
lizard (Anolis carolinensis)	Reptilia	GCK⁶	--	86(a)	1 ↔ 1	GL343238.1(356106-379706)
African clawed frog (Xenopus laevis)	Amphibia	gck-A²	glucokinase	78.84(n)		X93494.1
zebrafish (Danio rerio)	Actinopterygii	gck¹	glucokinase (hexokinase 4, maturity onset diabetes more	75.07(n) 83.71(a)		751668 NM_001045385.2 NP_001038850.2
fruit fly (Drosophila melanogaster)	Insecta	Hex-A³ Hex-C¹	hexokinase³ Hexokinase C¹	47(a) (best of 4)³ 56.54(n)¹ 46.87(a)¹		1 8E10³ 44008¹ NM_079935.3¹ NP_524674.1¹
worm (Caenorhabditis elegans)	Secernentea	F14B4.2³	hexokinase	45(a) (best of 3)		I(9279949-9281838) --
thale cress (Arabidopsis thaliana)	eudicotyledons	HXK3¹	hexokinase-like 1 protein	45.03(n) 37.02(a)		841200 NM_103682.3 NP_175220.2
rice (Oryza sativa)	Liliopsida	Os07g0197100¹	hypothetical protein	49.55(n) 38.64(a)		4342654 NM_001065659.1 NP_001059124.1

ENSEMBL Gene Tree for GCK (if available)
TreeFam Gene Tree for GCK (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for GCK gene

HK3² HK2² HKDC1² HK1²

5 SIMAP similar genes for GCK using alignment to 6 protein entries: HXK4_HUMAN (see all proteins):

HK2 DKFZp686M1669 HKDC1 HK1 HK3

GCK for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 7 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs104894014^1,2	C	pathogenic	44224266(-)	`GGTGGC/TCTGTA`	6	A V	mis¹		0	--	--	--	--
rs104894012^1,2	C	pathogenic	44224270(-)	`CGGCGA/GTGGCC`	6	M V	mis¹		0	--	--	--	--
rs104894016^1,2	C	pathogenic	44224717(-)	`CGCGCA/GCTGCG`	6	T A	mis¹		0	--	--	--	--
rs104894009^1,2	C	pathogenic	44225686(-)	`ACATGC/GGCGAG`	6	R G	mis¹		0	--	--	--	--
rs104894005^1,2	C,F,	pathogenic	44226777(-)	`TGGACC/G/TAGAGC`	9	Q E *	mis¹ stg¹		1		NA	4550
rs104894011^1,2	C	pathogenic	44226819(-)	`CCGGCG/TAGCTG`	6	E *	stg¹		0	--	--	--	--
rs104894008^1,2	C	pathogenic	44226831(-)	`CCTTCA/GGGGAC`	6	R G	mis¹		0	--	--	--	--
rs80356655^1,2	C	pathogenic	44226929(-)	`AGGCAC/TGGGCT`	6	T M	mis¹		0	--	--	--	--
rs148311934^1,2	C	pathogenic	44228862(+)	`ACCCAC/TGATCA`	6	M V	mis¹		1		NA	4550
rs144723656^1,2	C,F,	pathogenic	44228893(+)	`TCTTCA/C/GTAGTA`	9	Y *	stg¹ syn¹		2		NA EU	5875

HapMap Linkage Disequilibrium report for GCK (44183870 - 44237769 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for GCK
1 CNV: 4532
Human Gene Mutation Database (HGMD): GCK

Locus Specific Mutation Databases (LSDB): GCK

SABiosciences Cancer Mutation PCR Assays

Search QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing GCK

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

GCK for disorders           About GeneDecksing

OMIM gene information: 138079
OMIM disorders: 125851  125853  602485  606176
UniProtKB/Swiss-Prot: HXK4_HUMAN, P35557

Defects in GCK are the cause of maturity-onset diabetes of the young type 2 (MODY2) [MIM:125851]; also

shortened MODY-2. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset

in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent

insulin-independence at the beginning of the disease

Defects in GCK are the cause of familial hyperinsulinemic hypoglycemia type 3 (HHF3) [MIM:602485]; also known

as persistent hyperinsulinemic hypoglycemia of infancy (PHHI) or congenital hyperinsulinism. HHF is the most common

cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from

recurrent episodes of hypoglycemia may occur

20/55 diseases for GCK (see all 55): About MalaCards

maturity-onset diabetes of the young persistent hyperinsulinemic hypoglycemia of infancy maturity-onset diabetes of the young, type 2 hyperinsulinemic hypoglycemia

diabetes mellitus diabetes mellitus, noninsulin-dependent, late onset hypoglycemia of infancy 3-hydroxyacyl-coa dehydrogenase deficiency

hypoglycemia diabetes mellitus, noninsulin-dependent pancreatitis leucine-sensitive hypoglycemia of infancy

hyperinsulinemic hypoglycemia familial 3 greig cephalopolysyndactyly syndrome permanent neonatal diabetes mellitus neonatal diabetes mellitus

sudden infant death syndrome glucose intolerance glomerulocystic kidney disease type 2 diabetes mellitus

3 diseases from the University of Copenhagen DISEASES database for GCK:

maturity-onset diabetes of the young Diabetes mellitus Hyperglycemia

10/28 Novoseek disease relationships for GCK gene (see all 28) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
niddm	87	225	8349034 (5), 8433729 (5), 9653619 (3), 1545870 (3) (see all 99)
neonatal diabetes mellitus	79.2	11	18571549 (2), 14517946 (1), 16602010 (1), 19496967 (1) (see all 7)
hyperglycemia	77.9	110	9049484 (4), 8720607 (3), 19309449 (3), 8826967 (3) (see all 52)
hyperinsulinism	73.1	29	19053014 (4), 19336674 (4), 18450771 (2), 14641012 (1) (see all 11)
hypoglycemia	65.8	54	14517946 (4), 15277402 (4), 19790256 (4), 19336674 (2) (see all 24)
neonatal hypoglycemia	64.7	1	19884385 (1)
impaired glucose tolerance	64.5	11	9653619 (1), 9049484 (1), 19564454 (1), 15983230 (1) (see all 7)
insulinoma	64.1	18	9325299 (3), 9166666 (2), 9113996 (2), 2185104 (1) (see all 11)
diabetes mellitus	62.2	24	8495817 (1), 10694920 (1), 18382660 (1), 19551638 (1) (see all 21)
insulin resistance	56	10	8720607 (2), 8712800 (1), 18406764 (1), 11289470 (1) (see all 8)

GeneTests: GCK

Familial Hyperinsulinism

Permanent Neonatal Diabetes Mellitus

Genetic Association Database (GAD): GCK
Human Genome Epidemiology (HuGE) Navigator: GCK (80 documents)

Export disorders for GCK gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for GCK gene, integrated from 9 sources (see all 721):
(articles sorted by number of sources associating them with GCK)

Utopia: connect your pdf to the dynamic
world of online information

Human glucokinase gene: isolation, characterization, and identification of two missense mutations linked to early-onset non- insulin-dependent (type 2) diabetes mellitus. (PubMed id 1502186)^{1, 2, 3, 4, 9} Stoffel M.... Bell G.I. (1992)
Identification of glucokinase mutation in subjects with post-renal transplantation diabetes mellitus. (PubMed id 11106831)^{1, 2, 4, 9} Nam J.H....Huh K.B. (2000)
Identification of glucokinase mutations in subjects with gestational diabetes mellitus. (PubMed id 8495817)^{1, 2, 9} Stoffel M.... Bell G.I. (1993)
Glucokinase mutations associated with non-insulin-dependent (type 2) diabetes mellitus have decreased enzymatic activity: implications for structure/function relationships. (PubMed id 8446612)^{1, 2, 9} Gidh-Jain M.... Pilkis S.J. (1993)
Genetic regulation of birth weight and fasting glucose by a common polymorphism in the islet cell promoter of the glucokinase gene. (PubMed id 15677518)^{1, 4, 9} Weedon M.N....Hattersley A.T. (2005)
Identification of novel polymorphisms in the glucokinase and glucose-6-phosphatase genes in infants who died suddenly and unexpectedly. (PubMed id 15918042)^{1, 4, 9} Forsyth L....Burchell A. (2005)
[Mutation screening of GCK gene in Chinese early-onset diabetes population] (PubMed id 16331569)^{1, 4, 9} Zheng T.S....Xiang K.S. (2005)
Neonatal diabetes mellitus due to complete glucokinase deficiency. (PubMed id 11372010)^{1, 2, 9} Njoelstad P.R.... Bell G.I. (2001)
Routine mutation screening of HNF-1alpha and GCK genes in MODY diagnosis: how effective are the techniques of DHPLC and direct sequencing used in combination? (PubMed id 11440371)^{1, 4, 9} Boutin P....Froguel P. (2001)
Hepatic glucokinase promoter polymorphism is associated with hepatic insulin resistance in Asian Indians. (PubMed id 11112984)^{1, 4, 9} Chiu K.C....Saad M.F. (2000)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 2645	HGNC: 4195	AceView: GCK	Ensembl:ENSG00000106633	euGenes: HUgn2645
ECgene: GCK	Kegg: 2645	H-InvDB: GCK

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for GCK	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/GCK
Wikipedia	http://en.wikipedia.org/wiki/Glucokinase

Intellectual Property for GCK gene
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Patent Information for GCK gene:
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GeneCards and IP:
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glucokinase (hexokinase 4)

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GCK (Gene Symbol)
Glucokinase (Hexokinase 4)
HK4
MODY2
Hexokinase Type IV
HK IV
HHF3
Maturity Onset Diabetes Of The Young 2
FGQTL3
GK
GLK
HKIV
HXKP
LGLK
ATP:D-Hexose 6-Phosphotransferase
Glucokinase
Hexokinase D, Pancreatic Isozyme
Hexokinase-4
Hexokinase-D
EC 2.7.1.2
Hexokinase-4
Hexokinase-D
EC 2.7.1

HYPERURICEMIA
Insulin Resistance
Hyperinsulinemia
Genetic Susceptibility
impaired glucose tolerance
Neonatal hypoglycemia
OBESITY
Insulinoma
Diabetes Gestational
Glucose Intolerance
Hyperglycemia
Familial Hyperinsulinism
insulin sensitivity
Ischemia
Diabetes Mellitus
Tumors
Neonatal diabetes mellitus
Hypoglycemia
Hyperammonemia
metabolic disorder
Necrosis
Liver Cirrhosis
Permanent Neonatal Diabetes Mellitus
NIDDM
Single Gene Defects
Diabetes Autoimmune
Cancer
Diabetes Mellitus Insulin-Dependent
Hyperinsulinism
rare disease

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GCK Gene

glucokinase (hexokinase 4)

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