Cancer Cell Metabolism Gene Database

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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 NOS2
Basic gene info.Gene symbolNOS2
Gene namenitric oxide synthase 2, inducible
SynonymsHEP-NOS|INOS|NOS|NOS2A
CytomapUCSC genome browser: 17q11.2
Genomic locationchr17 :26083791-26127555
Type of geneprotein-coding
RefGenesNM_000625.4,
NM_153292.1,
Ensembl idENSG00000007171
DescriptionNOS type IINOS, type IIhepatocyte NOSinducible NO synthaseinducible NOSnitric oxide synthase 2A (inducible, hepatocytes)nitric oxide synthase, induciblenitric oxide synthase, macrophagepeptidyl-cysteine S-nitrosylase NOS2
Modification date20141222
dbXrefs MIM : 163730
HGNC : HGNC
Ensembl : ENSG00000007171
HPRD : 01225
Vega : OTTHUMG00000132445
ProteinUniProt: P35228
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_NOS2
BioGPS: 4843
Gene Expression Atlas: ENSG00000007171
The Human Protein Atlas: ENSG00000007171
PathwayNCI Pathway Interaction Database: NOS2
KEGG: NOS2
REACTOME: NOS2
ConsensusPathDB
Pathway Commons: NOS2
MetabolismMetaCyc: NOS2
HUMANCyc: NOS2
RegulationEnsembl's Regulation: ENSG00000007171
miRBase: chr17 :26,083,791-26,127,555
TargetScan: NM_000625
cisRED: ENSG00000007171
ContextiHOP: NOS2
cancer metabolism search in PubMed: NOS2
UCL Cancer Institute: NOS2
Assigned class in ccmGDBA - This gene has a literature evidence and it belongs to cancer gene.
References showing role of NOS2 in cancer cell metabolism1. Gerner E (2007) Impact of dietary amino acids and polyamines on intestinal carcinogenesis and chemoprevention in mouse models. Biochemical Society Transactions 35: 322. go to article

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Phenotypic Information for NOS2(metabolism pathway, cancer, disease, phenome)
check002.gifCancer Description
Cancer CGAP: NOS2
Familial Cancer Database: NOS2
* 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 163730; gene.
163730; gene.
611162; phenotype.
611162; phenotype.
Orphanet
DiseaseKEGG Disease: NOS2
MedGen: NOS2 (Human Medical Genetics with Condition)
ClinVar: NOS2
PhenotypeMGI: NOS2 (International Mouse Phenotyping Consortium)
PhenomicDB: NOS2

Mutations for NOS2
* 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
* Inter-chromosomal variantions includes 'interchromosomal amplicon to amplicon', 'interchromosomal amplicon to non-amplified dna', 'interchromosomal insertion', 'Interchromosomal unknown type'.
- 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
pancreasNOS2chr172609377726093797chr6106805874106805894
pancreasNOS2chr172612048726120507NOS2chr172612075526120775
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 NOS2 related fusion information.
IDHead GeneTail Gene
AccessionGene_aqStart_aqEnd_aChromosome_atStart_atEnd_aGene_aqStart_aqEnd_aChromosome_atStart_atEnd_a
AK310926NOS212388172609793826220391TTC372386363359480012494830723
BF844302ZDHHC3177934496897644969038NOS275259172621802026218204

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
 
Mutation type/ Tissue IDbrcacnscervendomehaematopokidnLintestliverlungnsovarypancreprostskinstomathyrourina
Total # sample3     1 2 2     1
GAIN (# sample)3     1 1 1      
LOSS (# sample)        1 1     1
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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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=3

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check002.gifSomatic Mutation Counts per Tissue in COSMIC data
Stat. for Non-Synonymous SNVs
(# total SNVs=102)
Stat. for Synonymous SNVs
(# total SNVs=28)
Stat. for Deletions
(# total SNVs=3)
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
chr17:26114738-26114738p.E145K3
chr17:26094815-26094815p.P695S2
chr17:26086080-26086080p.R1061R2
chr17:26093539-26093539p.S748F2
chr17:26108129-26108129p.R266H2
chr17:26099431-26099431p.R536Q2
chr17:26089931-26089931p.S898F2
chr17:26108182-26108182p.P248P2
chr17:26110016-26110016p.R195H2
chr17:26090025-26090025p.E867K1

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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=3

Point Mutation/ Tissue ID1234567891011121314151617181920
# sample46182 9 3 125711 1212 13
# mutation461102 9 3 125711 1815 16
nonsynonymous SNV35171 6 2 11751  127 14
synonymous SNV11 31 3 1  92 1 68 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
chr17:26114738p.E145K2
chr17:26093545p.R1061R2
chr17:26086080p.P746L2
chr17:26089931p.S898F2
chr17:26105983p.P57L1
chr17:26110057p.R670R1
chr17:26084309p.R454C1
chr17:26094781p.A348V1
chr17:26098034p.P248S1
chr17:26107882p.A1092V1

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 NOS2 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 NOS2

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

ACAN,BGN,C1orf177,NPR3,ENPEP,FGFBP2,FRZB,
FXYD4,GSTTP2,LCTL,LOC643008,NOS2,PANX3,PHOSPHO1,
PRELP,PRSS54,RNF175,SCRG1,SLC6A18,USH1G,WWP2
AKAP1,ARIH2,C14orf39,CDNF,COL4A3,CPT1B,GBX1,
GRIP2,INCA1,KLHL21,MEF2D,NOS2,OIT3,PAIP2B,
PLCD4,PPARGC1A,PYGO1,RPUSD4,TMIE,TRAK1,USP19

BCL3,C17orf78,CASP10,CASP5,CEACAM20,CFB,DUOX2,
DUOXA2,HK2,INSC,LOC286002,MMP10,NFKBIZ,NLRP6,
NOS2,REG3G,SOCS1,TNIP3,TRIM40,XDH,ZC3H12A
APOL1,ASS1,BACE2,BATF2,CALR,CASP5,CLEC6A,
CRELD2,FAM26F,GRAMD2,GZMB,IFI30,IFITM1,LYPD5,
NOS2,PARP9,PSMB2,PSME2,RTEL1,STAT1,UBE2L6
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 NOS2
check002.gifCross-referenced pharmacological DB IDs from Uniprot
DB CategoryDB NameDB's ID and Url link
ChemistryBindingDB P35228; -.
ChemistryChEMBL CHEMBL2096621; -.
ChemistryGuidetoPHARMACOLOGY 1250; -.
ChemistryBindingDB P35228; -.
ChemistryChEMBL CHEMBL2096621; -.
ChemistryGuidetoPHARMACOLOGY 1250; -.
Organism-specific databasesPharmGKB PA164724093; -.
Organism-specific databasesPharmGKB PA164724093; -.
Organism-specific databasesCTD 4843; -.
Organism-specific databasesCTD 4843; -.

check002.gifDrug-Gene Interaction Network
* Gene Centered Interaction Network.
* Drug Centered Interaction Network.
DrugBank IDTarget NameDrug GroupsGeneric NameDrug Centered NetworkDrug Structure
DB00125nitric oxide synthase 2, inducibleapproved; nutraceuticalL-Arginine
DB00155nitric oxide synthase 2, inducibleapproved; nutraceuticalL-Citrulline
DB01110nitric oxide synthase 2, inducibleapproved; investigationalMiconazole
DB01234nitric oxide synthase 2, inducibleapproved; investigationalDexamethasone
DB01686nitric oxide synthase 2, inducibleexperimentalN,N-dimethylarginine
DB01835nitric oxide synthase 2, inducibleexperimental4r-Fluoro-N6-Ethanimidoyl-L-Lysine
DB01997nitric oxide synthase 2, inducibleexperimental3-Bromo-7-Nitroindazole
DB02044nitric oxide synthase 2, inducibleexperimentalN-(3-(Aminomethyl)Benzyl)Acetamidine
DB02207nitric oxide synthase 2, inducibleexperimental7-Nitroindazole
DB02234nitric oxide synthase 2, inducibleexperimentalEthylisothiourea
DB02462nitric oxide synthase 2, inducibleexperimentalThiocoumarin
DB02533nitric oxide synthase 2, inducibleexperimentalAminoguanidine
DB02539nitric oxide synthase 2, inducibleexperimentalS-Ethylisothiourea
DB02644nitric oxide synthase 2, inducibleexperimentalN-Omega-Propyl-L-Arginine
DB02692nitric oxide synthase 2, inducibleexperimental(6r,1'r,2's)-5,6,7,8 Tetrahydrobiopterin
DB03014nitric oxide synthase 2, inducibleexperimentalHeme
DB03100nitric oxide synthase 2, inducibleexperimental6-Nitroindazole
DB03144nitric oxide synthase 2, inducibleexperimentalN-Omega-Hydroxy-L-Arginine
DB03271nitric oxide synthase 2, inducibleexperimental7,8-Dihydro-L-Biopterin
DB03449nitric oxide synthase 2, inducibleexperimentalN-(4-(2-((3-Chlorophenylmethyl)Amino)Ethyl)Phenyl)-2-Thiophecarboxamidine
DB03953nitric oxide synthase 2, inducibleexperimentalL-Thiocitrulline
DB04400nitric oxide synthase 2, inducibleexperimental7,8-Dihydrobiopterin
DB04534nitric oxide synthase 2, inducibleexperimental5-Nitroindazole
DB06879nitric oxide synthase 2, inducibleexperimental5-(4'-AMINO-1'-ETHYL-5',8'-DIFLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLINE]-1-YLCARBONYL)PICOLINONITRILE
DB06916nitric oxide synthase 2, inducibleexperimentalN-[2-(1,3-BENZODIOXOL-5-YL)ETHYL]-1-[2-(1H-IMIDAZOL-1-YL)-6-METHYLPYRIMIDIN-4-YL]-D-PROLINAMIDE
DB07002nitric oxide synthase 2, inducibleexperimental4-({4-[(4-methoxypyridin-2-yl)amino]piperidin-1-yl}carbonyl)benzonitrile
DB07003nitric oxide synthase 2, inducibleexperimental(2S)-2-methyl-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine
DB07007nitric oxide synthase 2, inducibleexperimental(3R)-3-[(1,2,3,4-tetrahydroisoquinolin-7-yloxy)methyl]-2,3-dihydrothieno[2,3-f][1,4]oxazepin-5-amine
DB07008nitric oxide synthase 2, inducibleexperimental4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PYRIMIDINE
DB07011nitric oxide synthase 2, inducibleexperimental(3S)-1-(1,3-BENZODIOXOL-5-YLMETHYL)-3-[4-(1H-IMIDAZOL-1-YL)PHENOXY]PIPERIDINE
DB07029nitric oxide synthase 2, inducibleexperimental4-(1,3-BENZODIOXOL-5-YLOXY)-2-[4-(1H-IMIDAZOL-1-YL)PHENOXY]-6-METHYLPYRIMIDINE
DB07306nitric oxide synthase 2, inducibleexperimentalETHYL 4-[(4-CHLOROPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE
DB07318nitric oxide synthase 2, inducibleexperimentalN-[2-(4-AMINO-5,8-DIFLUORO-1,2-DIHYDROQUINAZOLIN-2-YL)ETHYL]-3-FURAMIDE
DB07388nitric oxide synthase 2, inducibleexperimentalETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATE
DB07389nitric oxide synthase 2, inducibleexperimentalN-[2-(6-AMINO-4-METHYLPYRIDIN-2-YL)ETHYL]-4-CYANOBENZAMIDE
DB07405nitric oxide synthase 2, inducibleexperimental1-(6-CYANO-3-PYRIDYLCARBONYL)-5',8'-DIFLUOROSPIRO[PIPERIDINE-4,2'(1'H)-QUINAZOLINE]-4'-AMINE
DB08214nitric oxide synthase 2, inducibleexperimental4-(1H-IMIDAZOL-1-YL)PHENOL
DB08750nitric oxide synthase 2, inducibleexperimental1-[4-(AMINOMETHYL)BENZOYL]-5'-FLUORO-1'H-SPIRO[PIPERIDINE-4,2'-QUINAZOLIN]-4'-AMINE
DB00997nitric oxide synthase 2, inducibleapproved; investigationalDoxorubicin
DB00435nitric oxide synthase 2, inducibleapprovedNitric Oxide
DB00227nitric oxide synthase 2, inducibleapproved; investigationalLovastatin


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Cross referenced IDs for NOS2
* 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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