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 ARG1

Basic gene info.	Gene symbol	ARG1
	Gene name	arginase 1
	Synonyms	-
	Cytomap	UCSC genome browser: 6q23
	Genomic location	chr6 :131894343-131905472
	Type of gene	protein-coding
	RefGenes	NM_000045.3, NM_001244438.1,
	Ensembl id	ENSG00000118520
	Description	arginase, liverarginase-1liver-type arginasetype I arginase
	Modification date	20141219
dbXrefs	MIM : 608313
	HGNC : HGNC
	Ensembl : ENSG00000118520
	HPRD : 01947
	Vega : OTTHUMG00000015566
Protein	UniProt: P05089 go to UniProt's Cross Reference DB Table
Expression	CleanEX: HS_ARG1
	BioGPS: 383
	Gene Expression Atlas: ENSG00000118520
	The Human Protein Atlas: ENSG00000118520
Pathway	NCI Pathway Interaction Database: ARG1
	KEGG: ARG1
	REACTOME: ARG1
	ConsensusPathDB
	Pathway Commons: ARG1
Metabolism	MetaCyc: ARG1
	HUMANCyc: ARG1
Regulation	Ensembl's Regulation: ENSG00000118520
	miRBase: chr6 :131,894,343-131,905,472
	TargetScan: NM_000045
	cisRED: ENSG00000118520
Context	iHOP: ARG1
	cancer metabolism search in PubMed: ARG1
	UCL Cancer Institute: ARG1
Assigned class in ccmGDB	A - This gene has a literature evidence and it belongs to cancer gene.
References showing role of ARG1 in cancer cell metabolism	1. Stenmark KR, Tuder RM, El Kasmi KC (2015) Metabolic Reprogramming and Inflammation Act in Concert to Control Vascular Remodeling in Hypoxic Pulmonary Hypertension. J Appl Physiol (1985): jap 00283 02015. doi: 10.1152/japplphysiol.00283.2015. go to article

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Phenotypic Information for ARG1(metabolism pathway, cancer, disease, phenome)

Cancer Description
Cancer	CGAP: ARG1
	Familial Cancer Database: ARG1

* 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_ARGININE_AND_PROLINE_METABOLISM REACTOME_METABOLISM_OF_AMINO_ACIDS_AND_DERIVATIVES

Others
OMIM	207800; phenotype. 608313; gene.
Orphanet	90; Argininemia.
Disease	KEGG Disease: ARG1
	MedGen: ARG1 (Human Medical Genetics with Condition)
	ClinVar: ARG1
Phenotype	MGI: ARG1 (International Mouse Phenotyping Consortium)
Phenotype	PhenomicDB: ARG1

Mutations for ARG1

* 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	ARG1	chr6	131904653	131904673	MED23	chr6	131906140	131906160

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 ARG1 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=2

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Somatic Mutation Counts per Tissue in COSMIC data

Stat. for Non-Synonymous SNVs (# total SNVs=30)	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
chr6:131904603-131904603	p.L258L	2
chr6:131904251-131904251	p.D204E	2
chr6:131897815-131897815	p.V24L	2
chr6:131902413-131902413	p.V120V	2
chr6:131897818-131897818	p.E25K	2
chr6:131894467-131894467	p.F15L	2
chr6:131894472-131894472	p.K17T	1
chr6:131904598-131904598	p.G257S	1
chr6:131902355-131902355	p.?	1
chr6:131903792-131903792	p.T166I	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		2		3									3	1			2	2		4
# mutation		2		3									3	1			2	2		5
nonsynonymous SNV		2		2									2	1			1	2		4
synonymous SNV				1									1				1			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
chr6:131897815	p.V24L,ARG1	2
chr6:131900335	p.A112V,ARG1	1
chr6:131904949	p.P144L,ARG1	1
chr6:131900371	p.F162L,ARG1	1
chr6:131904954	p.T166I,ARG1	1
chr6:131902388	p.T201T,ARG1	1
chr6:131904992	p.K223K,ARG1	1
chr6:131902484	p.G235R,ARG1	1
chr6:131903781	p.G257S,ARG1	1
chr6:131903792	p.G283G,ARG1	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 ARG1 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 ARG1

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


APCS,APOA2,APOA4,APOB,APOC3,ARG1,C8A, C9,CREB3L3,CRP,F2,FABP1,FGF23,GDF2, HP,ITIH1,MT1B,PLG,SERPINA7,SLC17A2,TM4SF5	ALMS1,ANKRD36,ARG1,CCDC38,CDCA7,CENPJ,CCP110, FLJ10213,HIST3H3,INPP5F,INTS8,MC2R,RBBP6,SCML2, SHPRH,SNX18,USP17L6P,XPO1,XRCC2,ZBTB10,ZNF318

AJAP1,ARG1,AVPR1A,CCDC155,CLEC4D,CXCR1,CXCR2, SUPT20HL2,FPR1,FPR2,HRH2,IL7R,LINGO4,MGAM, OPN5,PADI4,PGLYRP1,S100A12,SELE,TCTE1,TNC	SLC35G3,ARG1,BEND2,LINC00305,CMTM2,CXCR2,FAM74A4, GAGE10,LRIT1,NXF4,OR52E2,OR52E6,PADI4,PLCZ1, SELE,SLC22A24,SPRR2G,SSX5,STRA8,TREML4,ZNF735

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 ARG1

Cross-referenced pharmacological DB IDs from Uniprot

DB Category	DB Name	DB's ID and Url link
Chemistry	BindingDB	P05089; -.
Chemistry	ChEMBL	CHEMBL1075097; -.
Organism-specific databases	PharmGKB	PA24947; -.
Organism-specific databases	CTD	383; -.

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
DB00129	arginase, liver	approved; nutraceutical	L-Ornithine
DB01983	arginase, liver	experimental	2(S)-Amino-6-Boronohexanoic Acid
DB02381	arginase, liver	experimental	Nor-N-Omega-Hydroxy-L-Arginine
DB02499	arginase, liver	experimental	Dinor-N(Omega)-Hydroxy-L-Arginine
DB02689	arginase, liver	experimental	S-{2-[Amino(Dihydroxy)-Lambda~4~-Sulfanyl]Ethyl}-D-Cysteine
DB03144	arginase, liver	experimental	N-Omega-Hydroxy-L-Arginine
DB03731	arginase, liver	experimental	S-2-(Boronoethyl)-L-Cysteine
DB03904	arginase, liver	experimental	Urea
DB04197	arginase, liver	experimental	Descarboxy-nor-N(Omega)-Hydroxy-L-Arginine
DB04530	arginase, liver	experimental	S,S-(2-Hydroxyethyl)Thiocysteine
DB04585	arginase, liver	experimental	DEHYDRO-2(S)-AMINO-6-BORONOHEXANOIC ACID
DB04648	arginase, liver	experimental	S-propylamine-L-cysteine
DB01222	arginase, liver	approved; investigational	Budesonide
DB00588	arginase, liver	approved; investigational	Fluticasone Propionate
DB00716	arginase, liver	approved	Nedocromil
DB01001	arginase, liver	approved	Salbutamol
DB00125	arginase, liver	approved; nutraceutical	L-Arginine

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Cross referenced IDs for ARG1

* 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