Cancer Cell Metabolism Gene Database

  Cancer Cell Metabolism Gene DB

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Bioinformatics and Systems Medicine Laboratory Bioinformatics and Systems Medicine Laboratory

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 GLS
Basic gene info.Gene symbolGLS
Gene nameglutaminase
SynonymsAAD20|GAC|GAM|GLS1|KGA
CytomapUCSC genome browser: 2q32-q34
Genomic locationchr2 :191745546-191800015
Type of geneprotein-coding
RefGenesNM_001256310.1,
NM_014905.4,
Ensembl idENSG00000115419
DescriptionK-glutaminaseL-glutamine amidohydrolaseglutaminase Cglutaminase kidney isoform, mitochondrialglutaminase, phosphate-activated
Modification date20141222
dbXrefs MIM : 138280
HGNC : HGNC
Ensembl : ENSG00000115419
HPRD : 00700
Vega : OTTHUMG00000132701
ProteinUniProt:
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_GLS
BioGPS: 2744
Gene Expression Atlas: ENSG00000115419
The Human Protein Atlas: ENSG00000115419
PathwayNCI Pathway Interaction Database: GLS
KEGG: GLS
REACTOME: GLS
ConsensusPathDB
Pathway Commons: GLS
MetabolismMetaCyc: GLS
HUMANCyc: GLS
RegulationEnsembl's Regulation: ENSG00000115419
miRBase: chr2 :191,745,546-191,800,015
TargetScan: NM_001256310
cisRED: ENSG00000115419
ContextiHOP: GLS
cancer metabolism search in PubMed: GLS
UCL Cancer Institute: GLS
Assigned class in ccmGDBA - This gene has a literature evidence and it belongs to cancer gene.
References showing role of GLS in cancer cell metabolism1. Tanaka K, Sasayama T, Irino Y, Takata K, Nagashima H, et al. (2015) Compensatory glutamine metabolism promotes glioblastoma resistance to mTOR inhibitor treatment. J Clin Invest 125: 1591-1602. doi: 10.1172/JCI78239. pmid: 4396477. go to article
2. Xiang Y, Stine ZE, Xia J, Lu Y, O'Connor RS, et al. (2015) Targeted inhibition of tumor-specific glutaminase diminishes cell-autonomous tumorigenesis. J Clin Invest 125: 2293-2306. doi: 10.1172/JCI75836. pmid: 4497742. go to article
3. Chen Z, Wang Y, Warden C, Chen S (2015) Cross-talk between ER and HER2 regulates c-MYC-mediated glutamine metabolism in aromatase inhibitor resistant breast cancer cells. J Steroid Biochem Mol Biol 149: 118-127. doi: 10.1016/j.jsbmb.2015.02.004. pmid: 4380584. go to article

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Phenotypic Information for GLS(metabolism pathway, cancer, disease, phenome)
check002.gifCancer Description
Cancer CGAP: GLS
Familial Cancer Database: GLS
* 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/

check002.gifMetabolic Pathway Description
KEGG_ALANINE_ASPARTATE_AND_GLUTAMATE_METABOLISM
KEGG_ARGININE_AND_PROLINE_METABOLISM
KEGG_NITROGEN_METABOLISM
REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

check002.gifOthers
OMIM
Orphanet
DiseaseKEGG Disease: GLS
MedGen: GLS (Human Medical Genetics with Condition)
ClinVar: GLS
PhenotypeMGI: GLS (International Mouse Phenotyping Consortium)
PhenomicDB: GLS

Mutations for GLS
* 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.

check002.gifStructural Variants in COSMIC: go to COSMIC mutation histogram
There's no structural variation information in COSMIC data for this gene.

check002.gifRelated fusion transcripts : go to Chitars2.0
* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows GLS related fusion information.
IDHead GeneTail Gene
AccessionGene_aqStart_aqEnd_aChromosome_atStart_atEnd_aGene_aqStart_aqEnd_aChromosome_atStart_atEnd_a
AI564468IGBP11110X6938606769386176GLS1044102191785560191788667
DA218082CCDC132138979286168992883244GLS3905462191792032191792188
DA400572AHI11926135818721135818812GLS935472191765290191785771
BI481206GLS131582191759896191760395PEBP115954212118582465118582847
DC316034IFT204505172665888226662497GLS5035822191827556191827635
BE179808TNRC1810261754373545437606GLS2574262191762157191762328
AW999094SLC39A81595474103183326103183713GLS5326282191798856191798952

check002.gifOther DBs for Structural Variants
Structural Variants in Ensembl: go to Ensembl Structural variation
Structural Variants in dbVar: go to dbVar

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check002.gifCopy Number Variations in COSMIC: go to COSMIC mutation CNV/Expr
 
Mutation type/ Tissue IDbrcacnscervendomehaematopokidnLintestliverlungnsovarypancreprostskinstomathyrourina
Total # sample        2 1      
GAIN (# sample)        1 1      
LOSS (# sample)        1        
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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check002.gifSNV 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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check002.gifSomatic Mutation Counts per Tissue in COSMIC data
Stat. for Non-Synonymous SNVs
(# total SNVs=39)
Stat. for Synonymous SNVs
(# total SNVs=16)
Stat. for Deletions
(# total SNVs=1)
Stat. for Insertions
(# total SNVs=0)
There's no inserted snv.

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check002.gifTop 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 positionMutation(aa)Unique sampleID count
chr2:191759947-191759947p.E152D2
chr2:191792124-191792124p.V447V2
chr2:191792131-191792131p.P450T2
chr2:191795282-191795282p.I515I2
chr2:191819355-191819355p.S586S2
chr2:191792187-191792187p.F468F2
chr2:191819482-191819482p.G597G2
chr2:191792056-191792056p.E425K2
chr2:191818309-191818309p.L557I2
chr2:191792122-191792122p.V447L2

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check002.gifSNV 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 ID1234567891011121314151617181920
# sample21122 1 51 751  27 9
# mutation21122 1 51 751  28 10
nonsynonymous SNV1  21 1 51 641  27 7
synonymous SNV111 1      11    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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check002.gifTop 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 PositionMutation(aa)Unique sampleID count
chr2:191818309p.E425K,GLS2
chr2:191792056p.L557I2
chr2:191745874p.S138T,GLS1
chr2:191796274p.I339S,GLS1
chr2:191765419p.K539N,GLS1
chr2:191827611p.D141Y,GLS1
chr2:191792060p.T342N,GLS1
chr2:191759904p.R543Q,GLS1
chr2:191796330p.E152D,GLS1
chr2:191766711p.E421D,GLS1

check002.gifOther 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

check002.gifCopy Number for GLS 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 GLS

check002.gifGene 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.

check002.gifDifferential 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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check002.gifCNV 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
check002.gifCo-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

BSN,C2orf15,CA11,CACNA2D2,CFAP36,ENO2,FAM57B,
FLJ35390,GLS2,HCN2,MADD,MAP3K12,MAPK8IP1,NEURL1,
P4HTM,PDZD7,REEP2,RNF157,SPTBN4,STMN3,TMEM145
ANO1,BBS1,MGME1,C20orf96,CDK20,CHDH,DDX31,
GLS2,GRHL2,HKR1,KDM1A,LIMK2,LOC254559,LOC400752,
MKS1,MORN4,OVOL2,RBM23,SALL2,SEMA4A,ZNF346

AURKB,TEX40,FAM216A,C1QBP,EMX1,F12,GLS2,
HSPA4L,HTRA2,KHK,KLHL35,NPM3,NT5M,PLD6,
SLC43A1,SPR,TMEM180,TMEM64,WNT10B,WNT8B,ZNF232
ARX,CA8,CELSR1,CFC1B,CHRM1,CYP2W1,CYP39A1,
DSCAML1,FMOD,GLS2,GP2,KCNJ6,KLK15,LOC440925,
MARCH4,NOL4,PPFIA2,SYBU,TUSC3,ZNF473,ZNF550
check002.gifCo-Expressed gene's Protein-protein interaction 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

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check002.gifInteracting 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 GLS
check002.gifCross-referenced pharmacological DB IDs from Uniprot
DB CategoryDB NameDB's ID and Url link

check002.gifDrug-Gene Interaction Network
* Gene Centered Interaction Network.
* Drug Centered Interaction Network.
DrugBank IDTarget NameDrug GroupsGeneric NameDrug Centered NetworkDrug Structure
DB00142glutaminaseapproved; nutraceuticalL-Glutamic Acid
DB00149glutaminaseapproved; nutraceuticalL-Leucine
DB00130glutaminaseapproved; nutraceutical; investigationalL-Glutamine


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Cross referenced IDs for GLS
* 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



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