Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~

Cancer Cell Metabolism Gene Database

Cancer Cell Metabolism Gene DB

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	Gene Summary
	Phenotypic Information (metabolism pathway, cancer, disease, phenome)
	Mutations : SVs, CNVs, SNVs
	Gene expression: GE, Protein, DEGE, CNV vs GE
	Gene-Gene Network Information: Co-Expression Network, Interacting Genes & KEGG
	Pharmacological Information: Drug-Gene Network
	Cross referenced IDs

Gene Summary for GCK

Basic gene info.	Gene symbol	GCK
	Gene name	glucokinase (hexokinase 4)
	Synonyms	FGQTL3\|GK\|GLK\|HHF3\|HK4\|HKIV\|HXKP\|LGLK\|MODY2
	Cytomap	UCSC genome browser: 7p15.3-p15.1
	Genomic location	chr7 :44183869-44229022
	Type of gene	protein-coding
	RefGenes	NM_000162.3, NM_033507.1,NM_033508.1,
	Ensembl id	ENSG00000106633
	Description	ATP:D-hexose 6-phosphotransferaseHK IVglucokinasehexokinase D, pancreatic isozymehexokinase type IVhexokinase-4hexokinase-D
	Modification date	20141222
dbXrefs	MIM : 138079
	HGNC : HGNC
	Ensembl : ENSG00000106633
	HPRD : 00680
	Vega : OTTHUMG00000022903
Protein	UniProt: P35557 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_GCK
	BioGPS: 2645
	Gene Expression Atlas: ENSG00000106633
	The Human Protein Atlas: ENSG00000106633
Pathway	NCI Pathway Interaction Database: GCK
	KEGG: GCK
	REACTOME: GCK
	ConsensusPathDB
	Pathway Commons: GCK
Metabolism	MetaCyc: GCK
	HUMANCyc: GCK
Regulation	Ensembl's Regulation: ENSG00000106633
	miRBase: chr7 :44,183,869-44,229,022
	TargetScan: NM_000162
	cisRED: ENSG00000106633
Context	iHOP: GCK
	cancer metabolism search in PubMed: GCK
	UCL Cancer Institute: GCK
Assigned class in ccmGDB	B - This gene belongs to cancer gene.

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Phenotypic Information for GCK(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: GCK
	Familial Cancer Database: GCK

* This gene is included in those cancer gene databases.


Oncogene ¹	Tumor Suppressor gene ²	Cancer Gene Census ³	CancerGenes ⁴	Network of Cancer Gene ⁵	Significant driver gene in	Therapeutic Vulnerabilities in Cancer¹

cf) number; DB name
1 Oncogene; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
2 Tumor Suppressor gene; https://bioinfo.uth.edu/TSGene/,
3 Cancer Gene Census; http://www.nature.com/nrc/journal/v4/n3/abs/nrc1299.html,
4 CancerGenes; http://nar.oxfordjournals.org/content/35/suppl_1/D721.long,
5 Network of Cancer Gene; http://ncg.kcl.ac.uk/index.php,
1Therapeutic Vulnerabilities in Cancer; http://cbio.mskcc.org/cancergenomics/statius/

Metabolic Pathway Description
KEGG_GLYCOLYSIS_GLUCONEOGENESIS KEGG_GALACTOSE_METABOLISM KEGG_STARCH_AND_SUCROSE_METABOLISM KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM REACTOME_METABOLISM_OF_CARBOHYDRATES

Others
OMIM	125851; phenotype. 138079; gene. 602485; phenotype. 606391; phenotype.
Orphanet	552; MODY syndrome. 79299; Hyperinsulinism due to glucokinase deficiency. 99885; Permanent neonatal diabetes mellitus.
Disease	KEGG Disease: GCK
	MedGen: GCK (Human Medical Genetics with Condition)
	ClinVar: GCK
Phenotype	MGI: GCK (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: GCK

Mutations for GCK

* Under tables are showing count per each tissue to give us broad intuition about tissue specific mutation patterns.You can go to the detailed page for each mutation database's web site.

Structural Variants in COSMIC : go to COSMIC mutation histogram

- Statistics for Tissue and Mutation type

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- For Inter-chromosomal Variations

There's no inter-chromosomal structural variation.

- For Intra-chromosomal Variations

* Intra-chromosomal variantions includes 'intrachromosomal amplicon to amplicon', 'intrachromosomal amplicon to non-amplified dna', 'intrachromosomal deletion', 'intrachromosomal fold-back inversion', 'intrachromosomal inversion', 'intrachromosomal tandem duplication', 'Intrachromosomal unknown type', 'intrachromosomal with inverted orientation', 'intrachromosomal with non-inverted orientation'.

Sample	Symbol_a	Chr_a	Start_a	End_a	Symbol_b	Chr_b	Start_b	End_b
ovary	GCK	chr7	44200584	44200604	GCK	chr7	44199791	44199811
pancreas	GCK	chr7	44210276	44210296		chr7	41067267	41067287

cf) Tissue number; Tissue name (1;Breast, 2;Central_nervous_system, 3;Haematopoietic_and_lymphoid_tissue, 4;Large_intestine, 5;Liver, 6;Lung, 7;Ovary, 8;Pancreas, 9;Prostate, 10;Skin, 11;Soft_tissue, 12;Upper_aerodigestive_tract)

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows GCK related fusion information.

Head Gene

Tail Gene

Accession

Gene_a

qStart_a

qEnd_a

Chromosome_a

tStart_a

tEnd_a

Gene_a

qStart_a

qEnd_a

Chromosome_a

tStart_a

tEnd_a

BF885201

GCK

143

162

44184199

44184218

FRA10AC1

158

209

95450597

95450648

Other DBs for Structural Variants

Structural Variants in Ensembl: go to Ensembl Structural variation

Structural Variants in dbVar: go to dbVar

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Copy Number Variations in COSMIC : go to COSMIC mutation CNV/Expr

Mutation type/ Tissue ID

brca

cns

cerv

endome

haematopo

kidn

Lintest

liver

lung

ovary

pancre

prost

skin

stoma

thyro

urina

Total # sample

GAIN (# sample)

LOSS (# sample)

cf) Tissue ID; Tissue type (1; Breast, 2; Central_nervous_system, 3; Cervix, 4; Endometrium, 5; Haematopoietic_and_lymphoid_tissue, 6; Kidney, 7; Large_intestine, 8; Liver, 9; Lung, 10; NS, 11; Ovary, 12; Pancreas, 13; Prostate, 14; Skin, 15; Stomach, 16; Thyroid, 17; Urinary_tract)

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SNV Counts per Each Loci in COSMIC data : go to COSMIC point mutation

: Non-synonymous mutation, : Synonymous mutation, Circle size denotes number of samples.
Maximum mutation count=4

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=31)	Stat. for Synonymous SNVs (# total SNVs=31)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=0)
There's no deleted snv.	There's no inserted snv.

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Top 10 SNVs Having the Most Samples in COSMIC data

* When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site,primary_histology,mutation(aa),pubmedID.

GRCh37 position	Mutation(aa)	Unique sampleID count
chr7:44190669-44190669	p.F124F	4
chr7:44189604-44189604	p.V182V	3
chr7:44193018-44193018	p.L31L	3
chr7:44190569-44190569	p.E158K	3
chr7:44189392-44189392	p.E217K	2
chr7:44187302-44187302	p.L271L	2
chr7:44186118-44186118	p.S322S	2
chr7:44190560-44190560	p.D161N	2
chr7:44198715-44198715	p.A2V	2
chr7:44189575-44189575	p.R192Q	2

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SNV Counts per Each Loci in TCGA data

: non-synonymous mutation, : synonymous mutation, Circle size denotes number of samples.
maximum mutation count=3

Point Mutation/ Tissue ID	1	2	3	4	5	6	7	8	9	10	11	12	13	14	15	16	17	18	19	20
# sample	3	3		14	2		5		1			10	8	1			19	7		5
# mutation	3	3		14	2		5		1			10	9	1			24	8		7
nonsynonymous SNV		2		5	1		2					4	7	1			17	4		3
synonymous SNV	3	1		9	1		3		1			6	2				7	4		4

cf) Tissue ID; Tissue type (1; BLCA[Bladder Urothelial Carcinoma], 2; BRCA[Breast invasive carcinoma], 3; CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], 4; COAD[Colon adenocarcinoma], 5; GBM[Glioblastoma multiforme], 6; Glioma Low Grade, 7; HNSC[Head and Neck squamous cell carcinoma], 8; KICH[Kidney Chromophobe], 9; KIRC[Kidney renal clear cell carcinoma], 10; KIRP[Kidney renal papillary cell carcinoma], 11; LAML[Acute Myeloid Leukemia], 12; LUAD[Lung adenocarcinoma], 13; LUSC[Lung squamous cell carcinoma], 14; OV[Ovarian serous cystadenocarcinoma ], 15; PAAD[Pancreatic adenocarcinoma], 16; PRAD[Prostate adenocarcinoma], 17; SKCM[Skin Cutaneous Melanoma], 18:STAD[Stomach adenocarcinoma], 19:THCA[Thyroid carcinoma], 20:UCEC[Uterine Corpus Endometrial Carcinoma])

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Top 10 SNVs Having the Most Samples in TCGA data

* We represented just top 10 SNVs. When you move the cursor on each content, you can see more deailed mutation information on the Tooltip. Those are primary_site, primary_histology, mutation(aa), pubmedID.

Genomic Position	Mutation(aa)	Unique sampleID count
chr7:44193018	p.L30L,GCK	3
chr7:44190669	p.F123F,GCK	3
chr7:44186118	p.D113D,GCK	2
chr7:44191894	p.V181V,GCK	2
chr7:44189392	p.A2V	2
chr7:44189604	p.S321S,GCK	2
chr7:44198715	p.E216K,GCK	2
chr7:44190560	p.R43C,GCK	1
chr7:44228525	p.S433C,GCK	1
chr7:44186117	p.D278D,GCK	1

Other DBs for Point Mutations

Point Mutation Table of Ensembl: go to Ensembl variation table

Mutation of cBioPortal: go to cBioPortal's Cross-cancer alteration summary

Copy Number for GCK in TCGA

* Copy number data were extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered on Jan-05-2015. Function ProcessCNAData in TCGA-Assembler package was used to obtain gene-level copy number value which is calculated as the average copy number of the genomic region of a gene.

cf) Tissue ID[Tissue type]: BLCA[Bladder Urothelial Carcinoma], BRCA[Breast invasive carcinoma], CESC[Cervical squamous cell carcinoma and endocervical adenocarcinoma], COAD[Colon adenocarcinoma], GBM[Glioblastoma multiforme], Glioma Low Grade, HNSC[Head and Neck squamous cell carcinoma], KICH[Kidney Chromophobe], KIRC[Kidney renal clear cell carcinoma], KIRP[Kidney renal papillary cell carcinoma], LAML[Acute Myeloid Leukemia], LUAD[Lung adenocarcinoma], LUSC[Lung squamous cell carcinoma], OV[Ovarian serous cystadenocarcinoma ], PAAD[Pancreatic adenocarcinoma], PRAD[Prostate adenocarcinoma], SKCM[Skin Cutaneous Melanoma], STAD[Stomach adenocarcinoma], THCA[Thyroid carcinoma], UCEC[Uterine Corpus Endometrial Carcinoma]

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Gene Expression for GCK

Gene Expression in Cancer Cell-lines (CCLE)

* CCLE gene expression data were extracted from CCLE_Expression_Entrez_2012-10-18.res: Gene-centric RMA-normalized mRNA expression data.

Differential Gene Expression in Primary Tumors (TCGA)

* Normalized gene expression data of RNASeqV2 was extracted from TCGA using R package TCGA-Assembler. The URLs of all public data files on TCGA DCC data server were gathered at Jan-05-2015. Only eight cancer types have enough normal control samples for differential expression analysis.
(t test, adjusted p<0.05 (using Benjamini-Hochberg FDR))

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CNV vs Gene Expression Plot

* This plots show the correlation between CNV and gene expression.

: Open all plots for all cancer types

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Gene-Gene Network Information

Co-Expressed gene's network Plot

* Co-Expression network figures were drawn using R package igraph. Only the top 20 genes with the highest correlations were shown.
Red circle: input gene, orange circle: cell metabolism gene, sky circle: other gene

: Open all plots for all cancer types


APCS,APOA1,APOA2,APOA4,APOB,APOC3,C3P1, C8A,C9,CREB3L3,CRP,F2,FABP1,FGF23, GCKR,HP,ITIH3,MT1B,PLG,SERPINA7,SULT2A1	BMP1,C14orf177,C6,C7,CETP,CTSL,FLVCR2, GCKR,GPR64,HMOX1,HTRA3,INSL4,KIR3DP1,MAPK11, OR2AG1,OR8D1,RHOXF2B,SCARNA20,SNORA19,SPATA8,TMEM114

ADIPOR2,ANKRD2,C12orf5,CACNA1C,CHRNA6,DCP1B,FBXL14, FKBP4,FOXM1,GCKR,GPR139,MEGF11,NKX6-3,OR9K2, PARP11,PPY,TEAD4,TMEM132B,TMEM173,TTTY6B,TULP3	AFP,APC,CA3,DNAJB3,FAM66E,GCKR,GOLGA6L1, IQUB,CEP104,LOC100128573,LINC01312,MGC45800,NHLH1,OGDH, RIPPLY1,SENP2,SGMS2,SNRK,ST7-OT4,TMEM86B,UGT1A1

Co-Expressed gene's Protein-protein interaction Network Plot

: Open all plots for all cancer types

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Interacting Genes (from Pathway Commons)

: Open all interacting genes' information including KEGG pathway for all interacting genes from DAVID

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Pharmacological Information for GCK

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P35557; -.
Chemistry	ChEMBL	CHEMBL3820; -.
Organism-specific databases	PharmGKB	PA28610; -.
Organism-specific databases	CTD	2645; -.

Drug-Gene Interaction Network

* Gene Centered Interaction Network.

* Drug Centered Interaction Network.

DrugBank ID	Target Name	Drug Groups	Generic Name	Drug Centered Network	Drug Structure
DB02379	glucokinase (hexokinase 4)	experimental	Beta-D-Glucose
DB07358	glucokinase (hexokinase 4)	experimental	2-amino-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide
DB07359	glucokinase (hexokinase 4)	experimental	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
DB08118	glucokinase (hexokinase 4)	experimental	2-(methylamino)-N-(4-methyl-1,3-thiazol-2-yl)-5-[(4-methyl-4H-1,2,4-triazol-3-yl)sulfanyl]benzamide
DB08210	glucokinase (hexokinase 4)	experimental	2-AMINO-4-FLUORO-5-[(1-METHYL-1H-IMIDAZOL-2-YL)SULFANYL]-N-(1,3-THIAZOL-2-YL)BENZAMIDE

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Cross referenced IDs for GCK

* We obtained these cross-references from Uniprot database. It covers 150 different DBs, 18 categories. http://www.uniprot.org/help/cross_references_section

: Open all cross reference information