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 G6PD

Basic gene info.	Gene symbol	G6PD
	Gene name	glucose-6-phosphate dehydrogenase
	Synonyms	G6PD1
	Cytomap	UCSC genome browser: Xq28
	Genomic location	chrX :153759605-153775787
	Type of gene	protein-coding
	RefGenes	NM_000402.4, NM_001042351.2,
	Ensembl id	ENSG00000269087
	Description	glucose-6-phosphate 1-dehydrogenase
	Modification date	20141222
dbXrefs	MIM : 305900
	HGNC : HGNC
	Ensembl : ENSG00000160211
	HPRD : 02377
	Vega : OTTHUMG00000024237
Protein	UniProt: P11413 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_G6PD
	BioGPS: 2539
	Gene Expression Atlas: ENSG00000269087
	The Human Protein Atlas: ENSG00000269087
Pathway	NCI Pathway Interaction Database: G6PD
	KEGG: G6PD
	REACTOME: G6PD
	ConsensusPathDB
	Pathway Commons: G6PD
Metabolism	MetaCyc: G6PD
	HUMANCyc: G6PD
Regulation	Ensembl's Regulation: ENSG00000269087
	miRBase: chrX :153,759,605-153,775,787
	TargetScan: NM_000402
	cisRED: ENSG00000269087
Context	iHOP: G6PD
	cancer metabolism search in PubMed: G6PD
	UCL Cancer Institute: G6PD
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of G6PD in cancer cell metabolism	1. Martin-Bernabe A, Cortes R, Lehmann SG, Seve M, Cascante M, et al. (2014) Quantitative proteomic approach to understand metabolic adaptation in non-small cell lung cancer. J Proteome Res 13: 4695-4704. doi: 10.1021/pr500327v. go to article 2. D'Alessandro A, Amelio I, Berkers CR, Antonov A, Vousden KH, et al. (2014) Metabolic effect of TAp63alpha: enhanced glycolysis and pentose phosphate pathway, resulting in increased antioxidant defense. Oncotarget 5: 7722-7733. pmid: 4202156. go to article 3. Cai T, Kuang Y, Zhang C, Zhang Z, Chen L, et al. (2015) Glucose-6-phosphate dehydrogenase and NADPH oxidase 4 control STAT3 activity in melanoma cells through a pathway involving reactive oxygen species, c-SRC and SHP2. Am J Cancer Res 5: 1610-1620. pmid: 4497430. go to article 4. Coda DM, Lingua MF, Morena D, Foglizzo V, Bersani F, et al. (2015) SMYD1 and G6PD modulation are critical events for miR-206-mediated differentiation of rhabdomyosarcoma. Cell Cycle 14: 1389-1402. doi: 10.1080/15384101.2015.1005993. go to article 5. Aird KM, Worth AJ, Snyder NW, Lee JV, Sivanand S, et al. (2015) ATM couples replication stress and metabolic reprogramming during cellular senescence. Cell Rep 11: 893-901. doi: 10.1016/j.celrep.2015.04.014. pmid: 4431925. go to article

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Phenotypic Information for G6PD(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: G6PD
	Familial Cancer Database: G6PD

* 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_GLUTATHIONE_METABOLISM REACTOME_METABOLISM_OF_CARBOHYDRATES

Others
OMIM	300908; phenotype. 305900; gene.
Orphanet	362; Glucose-6-phosphate-dehydrogenase deficiency.
Disease	KEGG Disease: G6PD
	MedGen: G6PD (Human Medical Genetics with Condition)
	ClinVar: G6PD
Phenotype	MGI: G6PD (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: G6PD

Mutations for G6PD

* 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 G6PD related fusion information.

ID	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
BQ352059	G6PD	1	68	X	153760922	153761445	G6PD	64	426	X	153761161	153762335
CA419747	ANAPC5	18	105	12	121746160	121746247	G6PD	105	789	X	153760136	153761273
M12996	G6PD	1	1671	X	153759627	153763408	PRKCA	1664	2439	17	64806066	64806841
BE816962	G6PD	8	152	X	153761181	153761325	G6PD	145	294	X	153761805	153762319
BM688674	G6PD	19	72	X	153759606	153759659	G6PD	64	236	X	153759955	153760127

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

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

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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=45)	Stat. for Synonymous SNVs (# total SNVs=9)

Stat. for Deletions (# total SNVs=1)	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
chr23:153761236-153761236	p.D324D	3
chr23:153760891-153760891	p.R393L	2
chr23:153760654-153760654	p.Y437Y	2
chr23:153760228-153760228	p.P512H	2
chr23:153760229-153760229	p.P512S	2
chr23:153762623-153762623	p.R192C	2
chr23:153762658-153762658	p.S180F	1
chr23:153764207-153764207	p.A71V	1
chr23:153760262-153760262	p.F501L	1
chr23:153762283-153762283	p.R246H	1

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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=2

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		1	1	13	1		2		2			2	1	4			5	2	1	8
# mutation		1	1	12	1		2		2			2	1	5			5	2	1	10
nonsynonymous SNV		1		12	1		1		2			2	1	5			4	1		7
synonymous SNV			1				1										1	1	1	3

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
chrX:153762623	p.R423H,G6PD	2
chrX:153760228	p.R222C,G6PD	2
chrX:153760229	p.P542H,G6PD	2
chrX:153760891	p.P542T,G6PD	2
chrX:153760233	p.V301M,G6PD	1
chrX:153763395	p.C188F,G6PD	1
chrX:153760920	p.V540V,G6PD	1
chrX:153762329	p.V289M,G6PD	1
chrX:153760260	p.P173P,G6PD	1
chrX:153763439	p.F531L,G6PD	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 G6PD 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 G6PD

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.

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Protein Expression Plot (RPPA)

*RPPA protein expression data were extracted from TCPA (The Cancer Proteome Atlas). Normalized data based on replicated based normalization (RBN) was used to draw following figures.

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


ACADL,AIFM1,AKR1C2,ALOX15B,DBI,ETFA,G6PD, GGCT,GGT1,ISX,KPNA7,ME1,MPHOSPH6,MVK, NSDHL,OXER1,PGD,POR,RLN3,SLED1,SPINK8	AACS,ABCC2,ADAM2,ALOX15B,DHRS2,FADS2,FDFT1, FIBCD1,G6PD,GGT1,GGTLC2,HIST1H3D,HPGD,MVD, MVK,NUDT8,PNLIPRP3,SERHL2,SERHL,SLC15A1,TARP

AIFM1,APEX2,ATP6AP1,BCAP31,CXorf40A,CXorf40B,EMD, G6PD,GLA,IDH3G,IKBKG,IRAK1,KIF4A,LAS1L, MTMR1,NSDHL,PRPS1,SLC10A3,SUV39H1,TMEM164,UBL4A	AP3D1,CARM1,CCNF,DPP9,FBXL19,G6PD,INCENP, LIMK1,MAD1L1,MTA2,NACC1,RANGAP1,RPS6KA4,SART1, SEC24C,TAPBP,TBC1D10B,TMEM104,TMEM214,TRIM56,VCP

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 G6PD

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P11413; -.
Chemistry	ChEMBL	CHEMBL5347; -.
Organism-specific databases	PharmGKB	PA28469; -.
Organism-specific databases	CTD	2539; -.

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
DB01582	glucose-6-phosphate dehydrogenase	approved	Sulfamethazine
DB00608	glucose-6-phosphate dehydrogenase	approved	Chloroquine
DB00250	glucose-6-phosphate dehydrogenase	approved; investigational	Dapsone
DB01033	glucose-6-phosphate dehydrogenase	approved	Mercaptopurine
DB00563	glucose-6-phosphate dehydrogenase	approved	Methotrexate
DB00783	glucose-6-phosphate dehydrogenase	approved; investigational	Estradiol
DB00675	glucose-6-phosphate dehydrogenase	approved	Tamoxifen
DB01087	glucose-6-phosphate dehydrogenase	approved	Primaquine

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Cross referenced IDs for G6PD

* 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