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 GSR

Basic gene info.	Gene symbol	GSR
	Gene name	glutathione reductase
	Synonyms	HEL-75
	Cytomap	UCSC genome browser: 8p21.1
	Genomic location	chr8 :30535579-30585486
	Type of gene	protein-coding
	RefGenes	NM_000637.3, NM_001195102.1,NM_001195103.1,NM_001195104.1,
	Ensembl id	ENSG00000104687
	Description	GRGRaseepididymis luminal protein 75glutathione reductase, mitochondrial
	Modification date	20141207
dbXrefs	MIM : 138300
	HGNC : HGNC
	Ensembl : ENSG00000104687
	HPRD : 00704
	Vega : OTTHUMG00000163946
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_GSR
	BioGPS: 2936
	Gene Expression Atlas: ENSG00000104687
	The Human Protein Atlas: ENSG00000104687
Pathway	NCI Pathway Interaction Database: GSR
	KEGG: GSR
	REACTOME: GSR
	ConsensusPathDB
	Pathway Commons: GSR
Metabolism	MetaCyc: GSR
	HUMANCyc: GSR
Regulation	Ensembl's Regulation: ENSG00000104687
	miRBase: chr8 :30,535,579-30,585,486
	TargetScan: NM_000637
	cisRED: ENSG00000104687
Context	iHOP: GSR
	cancer metabolism search in PubMed: GSR
	UCL Cancer Institute: GSR
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: GSR
	Familial Cancer Database: GSR

* 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_NUCLEOTIDES

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

Mutations for GSR

* 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

* Inter-chromosomal variantions includes 'interchromosomal amplicon to amplicon', 'interchromosomal amplicon to non-amplified dna', 'interchromosomal insertion', 'Interchromosomal unknown type'.

- 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	GSR	chr8	30540768	30540788	GSR	chr8	30556938	30556958
ovary	GSR	chr8	30577252	30577272	C12orf42	chr12	103752262	103752282

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 GSR 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

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=38)	Stat. for Synonymous SNVs (# total SNVs=12)

Stat. for Deletions (# total SNVs=1)	Stat. for Insertions (# total SNVs=1)

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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
chr8:30553994-30553994	p.R233H	3
chr8:30539537-30539537	p.E399Q	2
chr8:30537051-30537051	p.V519F	2
chr8:30553940-30553940	p.S251*	2
chr8:30541660-30541660	p.N366N	2
chr8:30557645-30557645	p.S216S	2
chr8:30537081-30537081	p.A509T	2
chr8:30541669-30541669	p.Q363H	2
chr8:30538562-30538562	p.?	2
chr8:30554006-30554006	p.?	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	1		5			2		2			6	5	1			4	7		5
# mutation	3	1		5			2		2			6	5	1			6	8		6
nonsynonymous SNV	2			3					2			5	4	1			3	5		5
synonymous SNV	1	1		2			2					1	1				3	3		1

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
chr8:30557645	p.S216S,GSR	3
chr8:30560722	p.F176F,GSR	2
chr8:30546693	p.T331I,GSR	1
chr8:30539450	p.S234S,GSR	1
chr8:30546715	p.E317Q,GSR	1
chr8:30537129	p.S221S,GSR	1
chr8:30557646	p.F280I,GSR	1
chr8:30539451	p.V411L,GSR	1
chr8:30546716	p.E279K,GSR	1
chr8:30537136	p.S216N,GSR	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 GSR 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 GSR

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


BNIP3L,CCDC25,DOPEY2,EIF2AK3,GSR,GTF2E2,HMBOX1, IDE,KIAA1244,PPP2CB,PRRC1,SCARB2,SEC16A,SEC24A, SH2D4A,SLC35F5,SPTLC2,TRIP11,UBR1,UBXN8,WRN	AHCY,ARSH,ASTN2,CENPO,CXCL6,FAM83A,FBN2, GSR,HIST1H2BH,HOXC10,HS6ST2,KCNJ13,KDM4A,LPAR3, MCM4,MUC6,PFKFB2,PRPS2,RACGAP1,SLC39A11,TIMELESS

AGPAT5,TTI2,CCDC25,DCTN6,ELP3,ERI1,ESCO2, FUT10,GSR,GTF2E2,INTS10,INTS9,LEPROTL1,MAK16, PBK,PPP2CB,PPP2R2A,SARAF,TNFRSF10A,UBXN8,XPO7	ACP1,AGR3,ARFIP2,C1orf131,CCDC125,GSR,H2AFY, JTB,KRTCAP3,MAPKAPK5,MGST2,NECAP1,NT5DC1,NUDT5, PDSS1,PI4K2B,SS18L2,TMEM106C,TOM1L1,TXNDC12,ZNF468

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 GSR

Cross-referenced pharmacological DB IDs from Uniprot

DB Category

DB Name

DB's ID and Url link

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
DB00143	glutathione reductase	approved; nutraceutical	Glutathione
DB00157	glutathione reductase	approved; nutraceutical	NADH
DB00262	glutathione reductase	approved	Carmustine
DB01644	glutathione reductase	experimental	3,6-Dihydroxy-Xanthene-9-Propionic Acid
DB01907	glutathione reductase	experimental	Nicotinamide-Adenine-Dinucleotide
DB02153	glutathione reductase	experimental	3-Sulfinoalanine
DB02553	glutathione reductase	experimental	Glutathionylspermidine Disulfide
DB02895	glutathione reductase	experimental	3-(Prop-2-Ene-1-Sulfinyl)-Propene-1-Thiol
DB03147	glutathione reductase	experimental	Flavin-Adenine Dinucleotide
DB03310	glutathione reductase	experimental	Oxidized Glutathione Disulfide
DB03867	glutathione reductase	experimental	Meta-Nitro-Tyrosine
DB07393	glutathione reductase	experimental	2-(2-PHENYL-3-PYRIDIN-2-YL-4,5,6,7-TETRAHYDRO-2H-ISOPHOSPHINDOL-1-YL)PYRIDINE
DB07714	glutathione reductase	experimental	6-(3-METHYL-1,4-DIOXO-1,4-DIHYDRONAPHTHALEN-2-YL)HEXANOIC ACID
DB00515	glutathione reductase	approved	Cisplatin

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Cross referenced IDs for GSR

* 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