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 MARS2

Basic gene info.	Gene symbol	MARS2
	Gene name	methionyl-tRNA synthetase 2, mitochondrial
	Synonyms	MetRS\|mtMetRS
	Cytomap	UCSC genome browser: 2q33.1
	Genomic location	chr2 :198570027-198573114
	Type of gene	protein-coding
	RefGenes	NM_138395.3,
	Ensembl id	ENSG00000247626
	Description	methionine tRNA ligase 2, mitochondrialmethionine--tRNA ligase 2methionine--tRNA ligase, mitochondrialmethionine-tRNA synthetase 2, mitochondrial
	Modification date	20141207
dbXrefs	MIM : 609728
	HGNC : HGNC
	Ensembl : ENSG00000247626
	HPRD : 14363
	Vega : OTTHUMG00000154487
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_MARS2
	BioGPS: 92935
	Gene Expression Atlas: ENSG00000247626
	The Human Protein Atlas: ENSG00000247626
Pathway	NCI Pathway Interaction Database: MARS2
	KEGG: MARS2
	REACTOME: MARS2
	ConsensusPathDB
	Pathway Commons: MARS2
Metabolism	MetaCyc: MARS2
	HUMANCyc: MARS2
Regulation	Ensembl's Regulation: ENSG00000247626
	miRBase: chr2 :198,570,027-198,573,114
	TargetScan: NM_138395
	cisRED: ENSG00000247626
Context	iHOP: MARS2
	cancer metabolism search in PubMed: MARS2
	UCL Cancer Institute: MARS2
Assigned class in ccmGDB	C

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Phenotypic Information for MARS2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: MARS2
	Familial Cancer Database: MARS2

* 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_SELENOAMINO_ACID_METABOLISM

Others
OMIM
Orphanet
Disease	KEGG Disease: MARS2
	MedGen: MARS2 (Human Medical Genetics with Condition)
	ClinVar: MARS2
Phenotype	MGI: MARS2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: MARS2

Mutations for MARS2

* 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

There's no inter-chromosomal structural variation.

- 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	MARS2	chr2	198571882	198571902		chr2	198576224	198576244
ovary	MARS2	chr2	198572000	198572020		chr2	198564793	198564813
ovary	MARS2	chr2	198572001	198572021		chr2	198564793	198564813

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 MARS2 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

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=3

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=34)	Stat. for Synonymous SNVs (# total SNVs=20)

Stat. for Deletions (# total SNVs=0)	Stat. for Insertions (# total SNVs=1)
There's no deleted 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
chr2:198570300-198570300	p.A57A	3
chr2:198571903-198571903	p.R592W	2
chr2:198571112-198571112	p.G328D	2
chr2:198571020-198571020	p.F297F	2
chr2:198571775-198571775	p.G549V	2
chr2:198570870-198570870	p.D247D	1
chr2:198571601-198571601	p.A491V	1
chr2:198571099-198571099	p.L324M	1
chr2:198570227-198570227	p.S33F	1
chr2:198571355-198571355	p.R409Q	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=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		1	1	6	1		5		4	1		12	2	3		1	4	3	1	6
# mutation		1	1	7	1		5		4	1		12	2	3		1	4	3	1	7
nonsynonymous SNV			1	5			3		3	1		9		3		1	4	2	1	4
synonymous SNV		1		2	1		2		1			3	2					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
chr2:198571112	p.F297F	2
chr2:198571571	p.R481Q	2
chr2:198571020	p.G328D	2
chr2:198571775	p.G549V	2
chr2:198570720	p.L197L	2
chr2:198571055	p.D271Y	1
chr2:198571363	p.A412T	1
chr2:198570234	p.S35S	1
chr2:198571806	p.S418C	1
chr2:198570761	p.I51T	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 MARS2 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 MARS2

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


ASNSD1,COA7,DDX21,GTF3C3,HSPD1,LRPPRC,MARS2, MOB4,NOLC1,NOP58,PNO1,POLR1B,PRPF40A,PUS7, RQCD1,SF3B1,URB2,WDR12,WDR43,WDR75,ZC3H15	BEND3,DSC2,FAM60A,LARS,MARS2,MCM4,MTMR1, NKRF,NOLC1,PAICS,POLR1B,PPAT,QTRTD1,SLC12A2, SMARCC1,SRPK1,SSX2IP,TEX10,URB2,USP10,ZBED4

C2orf47,CEBPZ,DDX18,FASTKD1,FASTKD2,HSPD1,LRPPRC, MARS2,METTL8,MRPL19,MRPL30,MTIF2,NOC3L,PNO1, PNPT1,POLR1B,PTCD3,SCLY,WDR12,WDR43,WDR75	AEN,AGPAT5,BYSL,FAM210A,FUT4,GRPEL1,KCNN4, MARS2,MECOM,PDE12,PIGW,PPIF,PUS1,RCL1, RDH13,RRP1,SEH1L,SLC25A19,TAF5L,URB2,UTP15

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 MARS2

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
DB00145	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	Glycine
DB00160	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Alanine
DB00125	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Arginine
DB00151	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Cysteine
DB00130	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical; investigational	L-Glutamine
DB00117	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Histidine
DB00149	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Leucine
DB00123	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Lysine
DB00134	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Methionine
DB00120	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Phenylalanine
DB00133	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Serine
DB00156	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Threonine
DB00150	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Tryptophan
DB00135	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Tyrosine
DB00161	methionyl-tRNA synthetase 2, mitochondrial	approved; nutraceutical	L-Valine

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Cross referenced IDs for MARS2

* 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