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 NOS3
Basic gene info.Gene symbolNOS3
Gene namenitric oxide synthase 3 (endothelial cell)
SynonymsECNOS|eNOS
CytomapUCSC genome browser: 7q36
Genomic locationchr7 :150690891-150701023
Type of geneprotein-coding
RefGenesNM_000603.4,
NM_001160109.1,NM_001160110.1,NM_001160111.1,
Ensembl idENSG00000164867
DescriptionEC-NOSNOS type IIINOSIIIcNOSconstitutive NOSendothelial NOSnitric oxide synthase 3 transcript variant eNOS-delta20nitric oxide synthase 3 transcript variant eNOS-delta20-21nitric oxide synthase 3 transcript variant eNOS-delta21nitric oxide syntha
Modification date20141222
dbXrefs MIM : 163729
HGNC : HGNC
Ensembl : ENSG00000164867
HPRD : 01224
Vega : OTTHUMG00000158343
ProteinUniProt: P29474
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_NOS3
BioGPS: 4846
Gene Expression Atlas: ENSG00000164867
The Human Protein Atlas: ENSG00000164867
PathwayNCI Pathway Interaction Database: NOS3
KEGG: NOS3
REACTOME: NOS3
ConsensusPathDB
Pathway Commons: NOS3
MetabolismMetaCyc: NOS3
HUMANCyc: NOS3
RegulationEnsembl's Regulation: ENSG00000164867
miRBase: chr7 :150,690,891-150,701,023
TargetScan: NM_000603
cisRED: ENSG00000164867
ContextiHOP: NOS3
cancer metabolism search in PubMed: NOS3
UCL Cancer Institute: NOS3
Assigned class in ccmGDBA - This gene has a literature evidence and it belongs to cancer gene.
References showing role of NOS3 in cancer cell metabolism1. Cole PD, Finkelstein Y, Stevenson KE, Blonquist TM, Vijayanathan V, et al. (2015) Polymorphisms in Genes Related to Oxidative Stress Are Associated With Inferior Cognitive Function After Therapy for Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology: JCO. 2014.2059. 0273. go to article

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Phenotypic Information for NOS3(metabolism pathway, cancer, disease, phenome)
check002.gifCancer Description
Cancer CGAP: NOS3
Familial Cancer Database: NOS3
* 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_ARGININE_AND_PROLINE_METABOLISM

check002.gifOthers
OMIM 163729; gene+phenotype.
163729; gene+phenotype.
Orphanet
DiseaseKEGG Disease: NOS3
MedGen: NOS3 (Human Medical Genetics with Condition)
ClinVar: NOS3
PhenotypeMGI: NOS3 (International Mouse Phenotyping Consortium)
PhenomicDB: NOS3

Mutations for NOS3
* 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

- Statistics for Tissue and Mutation typeTop
- 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'.
SampleSymbol_aChr_aStart_aEnd_aSymbol_bChr_bStart_bEnd_b
pancreasNOS3chr7150694249150694269WDR86chr7151082780151082800
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)

check002.gifRelated fusion transcripts : go to Chitars2.0
* From mRNA Sanger sequences, Chitars2.0 arranged chimeric transcripts. This table shows NOS3 related fusion information.
IDHead GeneTail Gene
AccessionGene_aqStart_aqEnd_aChromosome_atStart_atEnd_aGene_aqStart_aqEnd_aChromosome_atStart_atEnd_a
BU754328HLA-DPB11569645350014535055NOS3661857150691024150692384
BF955684NES81261156641010156641128NOS31223677150711426150711671

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
There's no copy number variation information in COSMIC data for this gene.

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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=6

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check002.gifSomatic Mutation Counts per Tissue in COSMIC data
Stat. for Non-Synonymous SNVs
(# total SNVs=100)		Stat. for Synonymous SNVs
(# total SNVs=24)
Stat. for Deletions
(# total SNVs=8)		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
chr7:150698398-150698398p.G440fs*646
chr7:150703567-150703567p.R602Q5
chr7:150696062-150696062p.G282E4
chr7:150706129-150706129p.E742Q3
chr7:150695726-150695726p.D258D3
chr7:150698505-150698505p.R474C3
chr7:150699340-150699340p.V567A2
chr7:150706116-150706116p.L737L2
chr7:150698983-150698983p.S526F2
chr7:150698429-150698429p.I448I2

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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
# sample74 137 5 51 1035  236 10
# mutation74 148 5 51 1035  256 13
nonsynonymous SNV53 116 4 21 813  155 11
synonymous SNV21 32 1 3  222  101 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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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
chr7:150693876p.R149W,NOS33
chr7:150695737p.S526F,NOS32
chr7:150698983p.I448I,NOS32
chr7:150706129p.R262Q,NOS32
chr7:150710862p.R1102R2
chr7:150698429p.V567A,NOS32
chr7:150699340p.E742Q2
chr7:150698337p.E301K,NOS31
chr7:150700767p.E432K,NOS31
chr7:150710902p.E498E,NOS31

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 NOS3 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 NOS3

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

ADCY4,ARHGEF15,BCL6B,CDH5,CLEC14A,CXorf36,ENG,
ERG,ESAM,EXOC3L2,GPR4,MMRN2,NOS3,NOTCH4,
PLVAP,ROBO4,S1PR1,SCARF1,SHANK3,TIE1,USHBP1		ACVRL1,ADCY4,ARHGEF15,CCM2L,CASKIN2,DHH,ENG,
ESAM,FAM65A,GJA4,HYAL2,LRRC32,MMRN2,NOS3,
NOVA2,PLVAP,RASIP1,SCARF1,SEMA6B,SH2D3C,TIE1

ATG9B,MRGPRG-AS1,LAMP5,C3orf35,CD68,CMAHP,CTSZ,
TMEM255A,FGF3,FSHR,LZTS1,MS4A3,NOS3,NOTCH3,
NRG3,OSCAR,OOSP2,SACS,SPANXN2,THSD1,VASH1		ABL2,MEDAG,CD248,CD93,ELFN1,ESAM,FBLN1,
FGF18,GFPT2,GPR4,KCNC4,MMRN2,MSX1,NES,
NOS3,NOVA2,PPRC1,RRP12,SLC7A1,SOX7,VEGFC
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 NOS3
check002.gifCross-referenced pharmacological DB IDs from Uniprot
DB CategoryDB NameDB's ID and Url link
ChemistryBindingDB P29474; -.
ChemistryChEMBL CHEMBL2111405; -.
ChemistryBindingDB P29474; -.
ChemistryChEMBL CHEMBL2111405; -.
Organism-specific databasesPharmGKB PA254; -.
Organism-specific databasesPharmGKB PA254; -.
Organism-specific databasesCTD 4846; -.
Organism-specific databasesCTD 4846; -.

check002.gifDrug-Gene Interaction Network
* Gene Centered Interaction Network.
* Drug Centered Interaction Network.
DrugBank IDTarget NameDrug GroupsGeneric NameDrug Centered NetworkDrug Structure
DB00125nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalL-Arginine
DB00155nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalL-Citrulline
DB00360nitric oxide synthase 3 (endothelial cell)approved; investigationalTetrahydrobiopterin
DB01110nitric oxide synthase 3 (endothelial cell)approved; investigationalMiconazole
DB01686nitric oxide synthase 3 (endothelial cell)experimentalN,N-dimethylarginine
DB01821nitric oxide synthase 3 (endothelial cell)experimentalL-N(Omega)-Nitroarginine-2,4-L-Diaminobutyric Amide
DB01833nitric oxide synthase 3 (endothelial cell)experimentalL-2-Amino-4-(Guanidinooxy)Butyric Acid
DB01997nitric oxide synthase 3 (endothelial cell)experimental3-Bromo-7-Nitroindazole
DB02027nitric oxide synthase 3 (endothelial cell)experimentalN-{(4s)-4-Amino-5-[(2-Aminoethyl)Amino]Pentyl}-N'-Nitroguanidine
DB02044nitric oxide synthase 3 (endothelial cell)experimentalN-(3-(Aminomethyl)Benzyl)Acetamidine
DB02048nitric oxide synthase 3 (endothelial cell)experimental1,2,4-Triazole-Carboxamidine
DB02077nitric oxide synthase 3 (endothelial cell)experimentalL-N(Omega)-Nitroarginine-(4r)-Amino-L-Proline Amide
DB02141nitric oxide synthase 3 (endothelial cell)experimentalS,S'-(1,4-Phenylene-Bis(1,2-Ethanediyl))Bis-Isothiourea
DB02207nitric oxide synthase 3 (endothelial cell)experimental7-Nitroindazole
DB02234nitric oxide synthase 3 (endothelial cell)experimentalEthylisothiourea
DB02335nitric oxide synthase 3 (endothelial cell)experimental2-Aminothiazoline
DB02589nitric oxide synthase 3 (endothelial cell)experimentalSe-Ethyl-Isoselenourea
DB02692nitric oxide synthase 3 (endothelial cell)experimental(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin
DB02911nitric oxide synthase 3 (endothelial cell)experimental2,4-Diamino-6-Phenyl-5,6,7,8,-Tetrahydropteridine
DB02979nitric oxide synthase 3 (endothelial cell)experimentalN1,N14-Bis((S-Methyl)Isothioureido)Tetradecane
DB02994nitric oxide synthase 3 (endothelial cell)experimentalHydroxydimethylarsine Oxide
DB03014nitric oxide synthase 3 (endothelial cell)experimentalHeme
DB03065nitric oxide synthase 3 (endothelial cell)experimental7-Nitroindazole-2-Carboxamidine
DB03100nitric oxide synthase 3 (endothelial cell)experimental6-Nitroindazole
DB03144nitric oxide synthase 3 (endothelial cell)experimentalN-Omega-Hydroxy-L-Arginine
DB03305nitric oxide synthase 3 (endothelial cell)experimentalN5-Iminoethyl-L-Ornithine
DB03332nitric oxide synthase 3 (endothelial cell)experimental5,6-Cyclic-Tetrahydropteridine
DB03707nitric oxide synthase 3 (endothelial cell)experimentalS-Ethyl-N-Phenyl-Isothiourea
DB03910nitric oxide synthase 3 (endothelial cell)experimentalS,S'-(1,3-Phenylene-Bis(1,2-Ethanediyl))Bis-Isothiourea
DB03918nitric oxide synthase 3 (endothelial cell)experimental6s-5,6,7,8-Tetrahydrobiopterin
DB03963nitric oxide synthase 3 (endothelial cell)experimentalS-(Dimethylarsenic)Cysteine
DB03974nitric oxide synthase 3 (endothelial cell)experimentalL-Homoarginine
DB04018nitric oxide synthase 3 (endothelial cell)experimentalS-Isopropyl-Isothiourea
DB04223nitric oxide synthase 3 (endothelial cell)experimentalNitroarginine
DB04534nitric oxide synthase 3 (endothelial cell)experimental5-Nitroindazole
DB04559nitric oxide synthase 3 (endothelial cell)experimentalN-(Chlorophenyl)-N'-Hydroxyguanidine
DB07001nitric oxide synthase 3 (endothelial cell)experimental(3S,5E)-3-propyl-3,4-dihydrothieno[2,3-f][1,4]oxazepin-5(2H)-imine
DB07244nitric oxide synthase 3 (endothelial cell)experimental5-{4-[(3,5-DIFLUOROBENZYL)AMINO]PHENYL}-6-ETHYLPYRIMIDINE-2,4-DIAMINE
DB07388nitric oxide synthase 3 (endothelial cell)experimentalETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE
DB08018nitric oxide synthase 3 (endothelial cell)experimentalN-{(3S,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N'-(4-CHLOROBENZYL)ETHANE-1,2-DIAMINE
DB08019nitric oxide synthase 3 (endothelial cell)experimentalN-{(3R,4S)-4-[(6-amino-4-methylpyridin-2-yl)methyl]pyrrolidin-3-yl}-N'-(3-chlorobenzyl)ethane-1,2-diamine
DB00999nitric oxide synthase 3 (endothelial cell)approvedHydrochlorothiazide
DB00119nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalPyruvic acid
DB00790nitric oxide synthase 3 (endothelial cell)approvedPerindopril
DB00584nitric oxide synthase 3 (endothelial cell)approvedEnalapril
DB00122nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalCholine
DB00394nitric oxide synthase 3 (endothelial cell)approvedBeclomethasone
DB01222nitric oxide synthase 3 (endothelial cell)approved; investigationalBudesonide
DB01410nitric oxide synthase 3 (endothelial cell)approved; investigationalCiclesonide
DB01260nitric oxide synthase 3 (endothelial cell)approved; investigationalDesonide
DB01234nitric oxide synthase 3 (endothelial cell)approved; investigationalDexamethasone
DB00180nitric oxide synthase 3 (endothelial cell)approved; investigationalFlunisolide
DB00588nitric oxide synthase 3 (endothelial cell)approved; investigationalFluticasone Propionate
DB00741nitric oxide synthase 3 (endothelial cell)approvedHydrocortisone
DB00443nitric oxide synthase 3 (endothelial cell)approvedBetamethasone
DB00959nitric oxide synthase 3 (endothelial cell)approvedMethylprednisolone
DB00764nitric oxide synthase 3 (endothelial cell)approvedMometasone
DB01384nitric oxide synthase 3 (endothelial cell)approvedParamethasone
DB00860nitric oxide synthase 3 (endothelial cell)approvedPrednisolone
DB00635nitric oxide synthase 3 (endothelial cell)approvedPrednisone
DB00896nitric oxide synthase 3 (endothelial cell)approvedRimexolone
DB00620nitric oxide synthase 3 (endothelial cell)approvedTriamcinolone
DB00131nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalAdenosine monophosphate
DB00435nitric oxide synthase 3 (endothelial cell)approvedNitric Oxide
DB00171nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalAdenosine triphosphate
DB01076nitric oxide synthase 3 (endothelial cell)approvedAtorvastatin
DB01098nitric oxide synthase 3 (endothelial cell)approvedRosuvastatin
DB00675nitric oxide synthase 3 (endothelial cell)approvedTamoxifen
DB01095nitric oxide synthase 3 (endothelial cell)approvedFluvastatin
DB00563nitric oxide synthase 3 (endothelial cell)approvedMethotrexate
DB00203nitric oxide synthase 3 (endothelial cell)approved; investigationalSildenafil
DB03128nitric oxide synthase 3 (endothelial cell)experimentalAcetylcholine
DB00727nitric oxide synthase 3 (endothelial cell)approved; investigationalNitroglycerin
DB00388nitric oxide synthase 3 (endothelial cell)approvedPhenylephrine
DB01275nitric oxide synthase 3 (endothelial cell)approvedHydralazine
DB01115nitric oxide synthase 3 (endothelial cell)approvedNifedipine
DB00531nitric oxide synthase 3 (endothelial cell)approved; investigationalCyclophosphamide
DB00997nitric oxide synthase 3 (endothelial cell)approved; investigationalDoxorubicin
DB00544nitric oxide synthase 3 (endothelial cell)approvedFluorouracil
DB00158nitric oxide synthase 3 (endothelial cell)approved; nutraceuticalFolic Acid


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Cross referenced IDs for NOS3
* 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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