TISIDB

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm Nucleus Note=Under low glucose concentrations, GCK associates with GKRP and the inactive complex is recruited to the hepatocyte nucleus.
Domain	PF00349 Hexokinase PF03727 Hexokinase
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 Ontology [ TOP ]
Biological Process	GO:0000271 polysaccharide biosynthetic process GO:0001678 cellular glucose homeostasis GO:0002790 peptide secretion GO:0002791 regulation of peptide secretion GO:0002793 positive regulation of peptide secretion GO:0005976 polysaccharide metabolic process GO:0005977 glycogen metabolic process GO:0005978 glycogen biosynthetic process GO:0005979 regulation of glycogen biosynthetic process GO:0005996 monosaccharide metabolic process GO:0006006 glucose metabolic process GO:0006007 glucose catabolic process GO:0006073 cellular glucan metabolic process GO:0006090 pyruvate metabolic process GO:0006091 generation of precursor metabolites and energy GO:0006094 gluconeogenesis GO:0006096 glycolytic process GO:0006109 regulation of carbohydrate metabolic process GO:0006110 regulation of glycolytic process GO:0006111 regulation of gluconeogenesis GO:0006112 energy reserve metabolic process GO:0006140 regulation of nucleotide metabolic process GO:0006165 nucleoside diphosphate phosphorylation GO:0006732 coenzyme metabolic process GO:0006733 oxidoreduction coenzyme metabolic process GO:0006734 NADH metabolic process GO:0006735 NADH regeneration GO:0006739 NADP metabolic process GO:0006757 ATP generation from ADP GO:0006813 potassium ion transport GO:0006816 calcium ion transport GO:0008643 carbohydrate transport GO:0008645 hexose transport GO:0009116 nucleoside metabolic process GO:0009118 regulation of nucleoside metabolic process GO:0009119 ribonucleoside metabolic process GO:0009123 nucleoside monophosphate metabolic process GO:0009126 purine nucleoside monophosphate metabolic process GO:0009132 nucleoside diphosphate metabolic process GO:0009135 purine nucleoside diphosphate metabolic process GO:0009141 nucleoside triphosphate metabolic process GO:0009144 purine nucleoside triphosphate metabolic process GO:0009150 purine ribonucleotide metabolic process GO:0009161 ribonucleoside monophosphate metabolic process GO:0009167 purine ribonucleoside monophosphate metabolic process GO:0009179 purine ribonucleoside diphosphate metabolic process GO:0009185 ribonucleoside diphosphate metabolic process GO:0009199 ribonucleoside triphosphate metabolic process GO:0009205 purine ribonucleoside triphosphate metabolic process GO:0009250 glucan biosynthetic process GO:0009306 protein secretion GO:0009730 detection of carbohydrate stimulus GO:0009732 detection of hexose stimulus GO:0009743 response to carbohydrate GO:0009746 response to hexose GO:0009749 response to glucose GO:0009894 regulation of catabolic process GO:0009914 hormone transport GO:0010675 regulation of cellular carbohydrate metabolic process GO:0010676 positive regulation of cellular carbohydrate metabolic process GO:0010677 negative regulation of cellular carbohydrate metabolic process GO:0010817 regulation of hormone levels GO:0010827 regulation of glucose transport GO:0010906 regulation of glucose metabolic process GO:0010907 positive regulation of glucose metabolic process GO:0010959 regulation of metal ion transport GO:0010962 regulation of glucan biosynthetic process GO:0015672 monovalent inorganic cation transport GO:0015749 monosaccharide transport GO:0015758 glucose transport GO:0015833 peptide transport GO:0015980 energy derivation by oxidation of organic compounds GO:0016051 carbohydrate biosynthetic process GO:0016052 carbohydrate catabolic process GO:0019318 hexose metabolic process GO:0019319 hexose biosynthetic process GO:0019320 hexose catabolic process GO:0019362 pyridine nucleotide metabolic process GO:0019674 NAD metabolic process GO:0023061 signal release GO:0030072 peptide hormone secretion GO:0030073 insulin secretion GO:0032024 positive regulation of insulin secretion GO:0032868 response to insulin GO:0032869 cellular response to insulin stimulus GO:0032881 regulation of polysaccharide metabolic process GO:0032885 regulation of polysaccharide biosynthetic process GO:0033500 carbohydrate homeostasis GO:0033692 cellular polysaccharide biosynthetic process GO:0034284 response to monosaccharide GO:0034287 detection of monosaccharide stimulus GO:0034637 cellular carbohydrate biosynthetic process GO:0042278 purine nucleoside metabolic process GO:0042593 glucose homeostasis GO:0042886 amide transport GO:0043255 regulation of carbohydrate biosynthetic process GO:0043266 regulation of potassium ion transport GO:0043434 response to peptide hormone GO:0043467 regulation of generation of precursor metabolites and energy GO:0043470 regulation of carbohydrate catabolic process GO:0044042 glucan metabolic process GO:0044262 cellular carbohydrate metabolic process GO:0044264 cellular polysaccharide metabolic process GO:0044282 small molecule catabolic process GO:0044283 small molecule biosynthetic process GO:0044320 cellular response to leptin stimulus GO:0044321 response to leptin GO:0044723 single-organism carbohydrate metabolic process GO:0044724 single-organism carbohydrate catabolic process GO:0045721 negative regulation of gluconeogenesis GO:0045725 positive regulation of glycogen biosynthetic process GO:0045912 negative regulation of carbohydrate metabolic process GO:0045913 positive regulation of carbohydrate metabolic process GO:0046031 ADP metabolic process GO:0046034 ATP metabolic process GO:0046128 purine ribonucleoside metabolic process GO:0046364 monosaccharide biosynthetic process GO:0046365 monosaccharide catabolic process GO:0046496 nicotinamide nucleotide metabolic process GO:0046835 carbohydrate phosphorylation GO:0046879 hormone secretion GO:0046883 regulation of hormone secretion GO:0046887 positive regulation of hormone secretion GO:0046939 nucleotide phosphorylation GO:0050708 regulation of protein secretion GO:0050714 positive regulation of protein secretion GO:0050796 regulation of insulin secretion GO:0051047 positive regulation of secretion GO:0051156 glucose 6-phosphate metabolic process GO:0051186 cofactor metabolic process GO:0051193 regulation of cofactor metabolic process GO:0051196 regulation of coenzyme metabolic process GO:0051222 positive regulation of protein transport GO:0051594 detection of glucose GO:0061615 glycolytic process through fructose-6-phosphate GO:0061620 glycolytic process through glucose-6-phosphate GO:0061621 canonical glycolysis GO:0061718 glucose catabolic process to pyruvate GO:0070509 calcium ion import GO:0070838 divalent metal ion transport GO:0070873 regulation of glycogen metabolic process GO:0070875 positive regulation of glycogen metabolic process GO:0071375 cellular response to peptide hormone stimulus GO:0071417 cellular response to organonitrogen compound GO:0072511 divalent inorganic cation transport GO:0072524 pyridine-containing compound metabolic process GO:0090087 regulation of peptide transport GO:0090276 regulation of peptide hormone secretion GO:0090277 positive regulation of peptide hormone secretion GO:1900542 regulation of purine nucleotide metabolic process GO:1901652 response to peptide GO:1901653 cellular response to peptide GO:1901657 glycosyl compound metabolic process GO:1903532 positive regulation of secretion by cell GO:1903578 regulation of ATP metabolic process GO:1904951 positive regulation of establishment of protein localization
Molecular Function	GO:0004340 glucokinase activity GO:0004396 hexokinase activity GO:0005536 glucose binding GO:0019200 carbohydrate kinase activity GO:0030246 carbohydrate binding GO:0048029 monosaccharide binding
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04910 Insulin signaling pathway hsa04911 Insulin secretion hsa04917 Prolactin signaling pathway hsa04922 Glucagon signaling pathway hsa00010 Glycolysis / Gluconeogenesis hsa00052 Galactose metabolism hsa00500 Starch and sucrose metabolism hsa00520 Amino sugar and nucleotide sugar metabolism hsa00524 Butirosin and neomycin biosynthesis hsa01100 Metabolic pathways hsa01200 Carbon metabolism
Reactome	R-HSA-5619107: Defective TRP may confer susceptibility towards thyroid papillary carcinoma (TPC) R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-5619115: Disorders of transmembrane transporters R-HSA-70326: Glucose metabolism R-HSA-70153: Glucose transport R-HSA-70171: Glycolysis R-HSA-189200: Hexose transport R-HSA-1430728: Metabolism R-HSA-71387: Metabolism of carbohydrates R-HSA-170822: Regulation of Glucokinase by Glucokinase Regulatory Protein R-HSA-186712: Regulation of beta-cell development R-HSA-210745: Regulation of gene expression in beta cells R-HSA-5619102: SLC transporter disorders R-HSA-425407: SLC-mediated transmembrane transport R-HSA-382551: Transmembrane transport of small molecules

> KEGG and Reactome Pathway

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KEGG

hsa04910 Insulin signaling pathway
hsa04911 Insulin secretion
hsa04917 Prolactin signaling pathway
hsa04922 Glucagon signaling pathway
hsa00010 Glycolysis / Gluconeogenesis
hsa00052 Galactose metabolism
hsa00500 Starch and sucrose metabolism
hsa00520 Amino sugar and nucleotide sugar metabolism
hsa00524 Butirosin and neomycin biosynthesis
hsa01100 Metabolic pathways
hsa01200 Carbon metabolism

Reactome

R-HSA-5619107: Defective TRP may confer susceptibility towards thyroid papillary carcinoma (TPC)
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5619115: Disorders of transmembrane transporters
R-HSA-70326: Glucose metabolism
R-HSA-70153: Glucose transport
R-HSA-70171: Glycolysis
R-HSA-189200: Hexose transport
R-HSA-1430728: Metabolism
R-HSA-71387: Metabolism of carbohydrates
R-HSA-170822: Regulation of Glucokinase by Glucokinase Regulatory Protein
R-HSA-186712: Regulation of beta-cell development
R-HSA-210745: Regulation of gene expression in beta cells
R-HSA-5619102: SLC transporter disorders
R-HSA-425407: SLC-mediated transmembrane transport
R-HSA-382551: Transmembrane transport of small molecules

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between GCK and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining [ TOP ]
There is no record.

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of GCK in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of GCK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.751	0.0364
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.655	0.00867
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.101	0.847
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.153	0.869
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.484	0.719
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.949	0.528
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.005	0.994
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.206	0.881
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.122	0.931
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.814	0.268
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	-0.814	0.415
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.04	0.787

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of GCK in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	4.1	-0.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	3.7	5.1	-1.4	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	0	7.7	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	7.7	-7.7	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	8.3	-8.3	1

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of GCK. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of GCK. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by GCK. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of GCK. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of GCK expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between GCK and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	GCK
Name	glucokinase (hexokinase 4)
Aliases	MODY2; maturity onset diabetes of the young 2; FGQTL3; HHF3; HKIV; HXKP; LGLK; HK IV; hexokinase D, pancreat ......
Chromosomal Location	7p15.3-p15.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting GCK collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting GCK.

ID	Name	Drug Type	Targets	#Targets
DB02379	Beta-D-Glucose	Small Molecule	AMY1A, AMY2A, AMY2B, GCK, GLT6D1, GNPDA1, HK1, IFNB1, KRTAP5-2, KR ......	22
DB07358	2-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide	Small Molecule	GCK	1
DB07359	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	Small Molecule	GCK	1
DB08118	2-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide	Small Molecule	GCK	1
DB08210	2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE	Small Molecule	GCK	1

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