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 GCLM

Basic gene info.	Gene symbol	GCLM
	Gene name	glutamate-cysteine ligase, modifier subunit
	Synonyms	GLCLR
	Cytomap	UCSC genome browser: 1p22.1
	Genomic location	chr1 :94352589-94375012
	Type of gene	protein-coding
	RefGenes	NM_002061.2,
	Ensembl id	ENSG00000023909
	Description	GCS light chainGSC light chaingamma-ECS regulatory subunitgamma-glutamylcysteine synthetase regulatory subunitglutamate--cysteine ligase modifier subunitglutamate--cysteine ligase regulatory subunitglutamate-cysteine ligase (gamma-glutamylcysteine s
	Modification date	20141207
dbXrefs	MIM : 601176
	HGNC : HGNC
	Ensembl : ENSG00000023909
	HPRD : 03106
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_GCLM
	BioGPS: 2730
	Gene Expression Atlas: ENSG00000023909
	The Human Protein Atlas: ENSG00000023909
Pathway	NCI Pathway Interaction Database: GCLM
	KEGG: GCLM
	REACTOME: GCLM
	ConsensusPathDB
	Pathway Commons: GCLM
Metabolism	MetaCyc: GCLM
	HUMANCyc: GCLM
Regulation	Ensembl's Regulation: ENSG00000023909
	miRBase: chr1 :94,352,589-94,375,012
	TargetScan: NM_002061
	cisRED: ENSG00000023909
Context	iHOP: GCLM
	cancer metabolism search in PubMed: GCLM
	UCL Cancer Institute: GCLM
Assigned class in ccmGDB	C

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

Cancer Description
Cancer	CGAP: GCLM
	Familial Cancer Database: GCLM

* 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_SULFUR_AMINO_ACID_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

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

Mutations for GCLM

* 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 GCLM 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
AA451832	SNTG2	3	72	2	1063989	1064058	GCLM	71	451	1	94353207	94353587
AI133413	SAMD9	8	665	7	92729970	92730629	GCLM	656	751	1	94354014	94354110

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=17)	Stat. for Synonymous SNVs (# total SNVs=4)

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
chr1:94354650-94354650	p.E241*	2
chr1:94362293-94362293	p.E141K	2
chr1:94354618-94354618	p.S251S	1
chr1:94362183-94362183	p.Q177H	1
chr1:94367183-94367183	p.E79Q	1
chr1:94354623-94354623	p.Y250D	1
chr1:94362191-94362191	p.L175M	1
chr1:94370097-94370097	p.I58I	1
chr1:94354629-94354629	p.L248M	1
chr1:94362251-94362251	p.Q155*	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=1

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	1		1			1		1		1	1	2	1			1	2		4
# mutation	2	1		1			1		1		1	1	2	1			1	2		4
nonsynonymous SNV	1	1		1			1				1	1	1	1			1	2		2
synonymous SNV	1								1				1							2

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
chr1:94354623	p.L200L	1
chr1:94367168	p.M196I	1
chr1:94360188	p.L190F	1
chr1:94370097	p.L175M	1
chr1:94360225	p.W147L	1
chr1:94370100	p.E141G	1
chr1:94360237	p.N137I	1
chr1:94360257	p.A128V	1
chr1:94362191	p.V116I	1
chr1:94362274	p.D84Y	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 GCLM 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 GCLM

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


DCUN1D1,DNTTIP2,DOCK7,DR1,GCLM,HIAT1,HS2ST1, LRRC40,LRRC58,LUZP6,MOB1A,NCKAP1,PKN2,ROCK2, RRAGC,RTCA,SASS6,TAF13,TMED5,TXNRD1,ZNF644	APC,CLINT1,DCUN1D1,DNM1L,EFR3A,FBXW11,GCLM, HIPK1,INTS2,KIF5B,MAPK1,NCKAP1,PPP2R5E,RNF141, RPRD1A,SCYL2,TNPO1,UEVLD,WDR44,ZBTB38,ZFP91

ABCD3,AGL,AHCYL1,MAB21L3,CLCC1,DBT,DNTTIP2, FNBP1L,GCLM,GPSM2,HOOK1,LRRC8D,NRAS,SIKE1, TMED5,TMEM56,TRIM33,VANGL1,WDR3,ZNF644,ZNHIT6	AGMAT,AIMP2,AK2,ALDH3A2,B4GALNT2,C2orf47,C2orf69, GLIS3-AS1,ETFA,ETNK1,FDX1,GCLM,HMGB3,LHFPL3, ME2,MGST1,MTCH2,OXNAD1,PITX2,TMED5,UGDH

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 GCLM

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
DB00142	glutamate-cysteine ligase, modifier subunit	approved; nutraceutical	L-Glutamic Acid
DB00151	glutamate-cysteine ligase, modifier subunit	approved; nutraceutical	L-Cysteine
DB00515	glutamate-cysteine ligase, modifier subunit	approved	Cisplatin
DB00143	glutamate-cysteine ligase, modifier subunit	approved; nutraceutical	Glutathione

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Cross referenced IDs for GCLM

* 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