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 EARS2

Basic gene info.	Gene symbol	EARS2
	Gene name	glutamyl-tRNA synthetase 2, mitochondrial
	Synonyms	COXPD12\|MSE1
	Cytomap	UCSC genome browser: 16p12.2
	Genomic location	chr16 :23533333-23568696
	Type of gene	protein-coding
	RefGenes	NM_001083614.1, NR_003501.1,
	Ensembl id	ENSG00000103356
	Description	gluRSglutamate tRNA ligase 2, mitochondrialglutamate--tRNA ligaseglutamyl-tRNA synthetase 2, mitochondrial (putative)probable glutamate--tRNA ligase, mitochondrialprobable glutamyl-tRNA synthetase, mitochondrial
	Modification date	20141207
dbXrefs	MIM : 612799
	HGNC : HGNC
	Ensembl : ENSG00000103356
	Vega : OTTHUMG00000177018
Protein	UniProt: go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_EARS2
	BioGPS: 124454
	Gene Expression Atlas: ENSG00000103356
	The Human Protein Atlas: ENSG00000103356
Pathway	NCI Pathway Interaction Database: EARS2
	KEGG: EARS2
	REACTOME: EARS2
	ConsensusPathDB
	Pathway Commons: EARS2
Metabolism	MetaCyc: EARS2
	HUMANCyc: EARS2
Regulation	Ensembl's Regulation: ENSG00000103356
	miRBase: chr16 :23,533,333-23,568,696
	TargetScan: NM_001083614
	cisRED: ENSG00000103356
Context	iHOP: EARS2
	cancer metabolism search in PubMed: EARS2
	UCL Cancer Institute: EARS2
Assigned class in ccmGDB	C

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Phenotypic Information for EARS2(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: EARS2
	Familial Cancer Database: EARS2

* 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_PORPHYRIN_AND_CHLOROPHYLL_METABOLISM

Others
OMIM
Orphanet
Disease	KEGG Disease: EARS2
	MedGen: EARS2 (Human Medical Genetics with Condition)
	ClinVar: EARS2
Phenotype	MGI: EARS2 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: EARS2

Mutations for EARS2

* 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 EARS2 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

AW605160

HMGB2

465

174253196

174254307

EARS2

453

561

23535431

23535539

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=2

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=25)	Stat. for Synonymous SNVs (# total SNVs=8)

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
chr16:23555840-23555840	p.T160T	2
chr16:23546599-23546599	p.R190C	2
chr16:23546255-23546255	p.P304P	1
chr16:23535757-23535757	p.E503Q	1
chr16:23563572-23563572	p.K65*	1
chr16:23541078-23541078	p.L403P	1
chr16:23546257-23546257	p.P304S	1
chr16:23536559-23536559	p.?	1
chr16:23555844-23555844	p.Q159R	1
chr16:23563615-23563615	p.H50H	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	3		3			2	1		1		4	3			1		6		5
# mutation	1	3		3			2	1		1		4	3			1		6		6
nonsynonymous SNV	1	3		2			1					3	3					3		5
synonymous SNV				1			1	1		1		1				1		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
chr16:23546599	p.R190C	2
chr16:23541092	p.E503Q	1
chr16:23546671	p.D216G	1
chr16:23535745	p.R489W	1
chr16:23543988	p.L201M	1
chr16:23555840	p.V449V	1
chr16:23535757	p.D200N	1
chr16:23546255	p.V444A	1
chr16:23555867	p.A429V	1
chr16:23536588	p.R166W	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 EARS2 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 EARS2

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


ALG1,FOPNL,KNOP1,COG7,COQ7,DNAJA3,EARS2, ERI2,GLYR1,GSPT1,HN1L,PARN,POLR3E,RRN3, THUMPD1,UBFD1,USP7,ZKSCAN2,ZNF174,ZNF263,ZSCAN32	BEND3,C10orf2,COBL,DAG1,DKC1,EARS2,GLB1L2, IPO4,KIAA1324,LARS,LIG3,MANEAL,MCM4,PAICS, PDCD11,PLCH1,PLEKHH1,POLR1B,SLC12A8,UCK2,WWC1

KNOP1,CCDC86,DHODH,DNAJA3,DPH2,EARS2,EEF2KMT, GOT2,GSPT1,HN1L,NUP93,PALB2,PDF,PLK1, POLR3E,RNF40,TMEM186,TRAP1,TUFM,UBFD1,XPO6	ABCE1,ACAD9,DDX10,DDX56,DHODH,DKC1,EARS2, FARSB,KIAA0020,NOP14,PAICS,PPIF,PRMT5,PRPF4, PUS1,PUS7,RRP9,SRFBP1,UTP14A,WDR3,WDR77

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 EARS2

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

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Cross referenced IDs for EARS2

* 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