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 HK2

Basic gene info.	Gene symbol	HK2
	Gene name	hexokinase 2
	Synonyms	HKII\|HXK2
	Cytomap	UCSC genome browser: 2p13
	Genomic location	chr2 :75059781-75120481
	Type of gene	protein-coding
	RefGenes	NM_000189.4,
	Ensembl id	ENSG00000159399
	Description	HK IIhexokinase type IIhexokinase-2hexokinase-2, musclemuscle form hexokinase
	Modification date	20141207
dbXrefs	MIM : 601125
	HGNC : HGNC
	Ensembl : ENSG00000159399
	HPRD : 03080
	Vega : OTTHUMG00000129972
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_HK2
	BioGPS: 3099
	Gene Expression Atlas: ENSG00000159399
	The Human Protein Atlas: ENSG00000159399
Pathway	NCI Pathway Interaction Database: HK2
	KEGG: HK2
	REACTOME: HK2
	ConsensusPathDB
	Pathway Commons: HK2
Metabolism	MetaCyc: HK2
	HUMANCyc: HK2
Regulation	Ensembl's Regulation: ENSG00000159399
	miRBase: chr2 :75,059,781-75,120,481
	TargetScan: NM_000189
	cisRED: ENSG00000159399
Context	iHOP: HK2
	cancer metabolism search in PubMed: HK2
	UCL Cancer Institute: HK2
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of HK2 in cancer cell metabolism	1. Kim H, Jang H, Kim TW, Kang BH, Lee SE, et al. (2015) Core Pluripotency Factors Directly Regulate Metabolism in Embryonic Stem Cell to Maintain Pluripotency. Stem Cells. doi: 10.1002/stem.2073. go to article 2. Zhuo B, Li Y, Li Z, Qin H, Sun Q, et al. (2015) PI3K/Akt signaling mediated Hexokinase-2 expression inhibits cell apoptosis and promotes tumor growth in pediatric osteosarcoma. Biochem Biophys Res Commun. doi: 10.1016/j.bbrc.2015.06.092 go to article 3. Guo W, Qiu Z, Wang Z, Wang Q, Tan N, et al. (2015) MiR-199a-5p is negatively associated with malignancies and regulates glycolysis and lactate production by targeting hexokinase 2 in liver cancer. Hepatology. doi: 10.1002/hep.27929. go to article 4. Alvarez JV, Belka GK, Pan TC, Chen CC, Blankemeyer E, et al. (2014) Oncogene pathway activation in mammary tumors dictates FDG-PET uptake. Cancer Res 74: 7583-7598. doi: 10.1158/0008-5472.CAN-14-1235. pmid: 4342047. go to article

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Phenotypic Information for HK2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: HK2
	Familial Cancer Database: HK2

* 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_FRUCTOSE_AND_MANNOSE_METABOLISM KEGG_GALACTOSE_METABOLISM KEGG_STARCH_AND_SUCROSE_METABOLISM KEGG_AMINO_SUGAR_AND_NUCLEOTIDE_SUGAR_METABOLISM REACTOME_METABOLISM_OF_CARBOHYDRATES

Others
OMIM
Orphanet
Disease	KEGG Disease: HK2
	MedGen: HK2 (Human Medical Genetics with Condition)
	ClinVar: HK2
Phenotype	MGI: HK2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: HK2

Mutations for HK2

* 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

There's no structural variation information in COSMIC data for this gene.

Related fusion transcripts : go to Chitars2.0

* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows HK2 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

Z46376

FAM50A

1069

153674037

153678996

HK2

1067

5289

75061284

75119113

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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=68)	Stat. for Synonymous SNVs (# total SNVs=27)

Stat. for Deletions (# total SNVs=2)	Stat. for Insertions (# total SNVs=0)
	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
chr2:75081444-75081444	p.R30C	3
chr2:75115108-75115108	p.L766L	3
chr2:75061718-75061718	p.S4L	3
chr2:75107455-75107455	p.L443L	2
chr2:75081481-75081481	p.R42Q	2
chr2:75113426-75113426	p.F647L	2
chr2:75109306-75109306	p.G593G	2
chr2:75061723-75061723	p.L6L	2
chr2:75118054-75118054	p.A914S	2
chr2:75105930-75105930	p.A383P	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	2	2		8	2		4		2			11	6	2			14	10	2	14
# mutation	2	2		9	2		4		2			13	6	2			15	13	2	14
nonsynonymous SNV	2	2		6	2		4					11	6	2			10	10	2	9
synonymous SNV				3					2			2					5	3		5

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
chr2:75061718	p.S4W	3
chr2:75113788	p.R702Q	2
chr2:75113686	p.P736H	2
chr2:75117984	p.F890F	2
chr2:75116443	p.R846Q	1
chr2:75061762	p.R42Q	1
chr2:75107651	p.S269L	1
chr2:75112659	p.L533L	1
chr2:75118006	p.R539L	1
chr2:75099521	p.D714G	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 HK2 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 HK2

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


AFF3,AHCYL2,ATP2C2,BCAS1,BZW1,CADPS,CLCN3, EPT1,GDPD1,GMCL1,GUF1,HK2,ISOC1,MAP4K3, KAT6B,RAB3A,RELL1,SYNJ2BP,TRIM36,ZFHX3,ZSWIM5	ACO1,AOC3,DMGDH,ESYT1,FZD4,GPAM,GPD1, HK2,LPL,MRAS,MTHFD1,NAT8L,PEX19,PLIN1, PRKAR2B,PXDN,PYGL,RBP4,TNS1,TSPAN3,VKORC1L1

BMP2,C4orf19,CASP5,CCL28,CEACAM1,CEACAM7,DUOX2, DUOXA2,GOLM1,HK2,ITM2C,LIMA1,MALL,NR3C2, PAPSS2,PIGR,PTPRH,RBM47,TMPRSS2,TRIM40,XDH	BAIAP2L1,CASP10,CEACAM1,CEACAM5,CEACAM6,CHD1,CLIC5, DNAJC3,DNAJC7,DTX3L,HK2,HPSE,LEO1,MUC1, RNF19B,RPS6KA4,SLCO2A1,TOP1,TRIM15,USP38,XDH

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 HK2

There's no related Drug.

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Cross referenced IDs for HK2

* 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