mutLBSgeneDB

mutLBSgeneDB
mutated Ligand Binding Site gene DataBase

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Gene Summary

Ligand Binding Site Mutation Information

Protein Structure Related Information

Gene Expression and Gene-Gene Network

Phenotype Information

Pharmacological Information

Conservation Information for LBS

Gene summary for NOS3
Gene summary
Basic gene Info.Gene symbolNOS3
Gene namenitric oxide synthase 3 (endothelial cell)
SynonymsECNOS|eNOS
CytomapUCSC genome browser: 7q36
Type of geneprotein-coding
RefGenesNM_000603.4,
NM_001160109.1,NM_001160110.1,NM_001160111.1,
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
PathwayNCI Pathway Interaction Database: NOS3
KEGG: NOS3
REACTOME: NOS3
Pathway Commons: NOS3
ContextiHOP: NOS3
ligand binding site mutation search in PubMed: NOS3
UCL Cancer Institute: NOS3
Assigned class in mutLBSgeneDBB: This gene belongs to targetable_mutLBSgenes.

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0006527arginine catabolic process1378832
GO:0006809nitric oxide biosynthetic process1378832


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Ligand binding site mutations for NOS3
Lollipop-style diagram of mutations at LBS in amino-acid sequence.
We represented ligand binding site mutations only. (You can see big image via clicking.)
 : non-synonymous mutation on LBS, Circle size denotes number of samples.

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
F473P471LCOAD1
Y475,F473R474GLUAD1
L193V195GLUAD1
Y475,F473R474POV1
R365R365KSKCM1
E361,R365G363SUCEC1
cf) Cancer type abbreviation. BLCA: Bladder urothelial carcinoma, BRCA: Breast invasive carcinoma, CESC: Cervical squamous cell carcinoma and endocervical adenocarcinoma, COAD: Colon adenocarcinoma, GBM: Glioblastoma multiforme, LGG: Brain lower grade glioma, 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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Protein structure related information for NOS3
Relative protein structure stability change (ΔΔE) using Mupro 1.1
Mupro score denotes assessment of the effect of mutations on thermodynamic stability.
  (ΔΔE<0: mutation decreases stability, ΔΔE>0: mutation increases stability)
: nsSNV at non-LBS: nsSNV at LBS

nsSNVs sorted by the relative stability change of protein structure by each mutation
Blue: mutations of positive stability change. and red : the most recurrent mutation for this gene.
LBSAAchange of nsSNVRelative stability change
R365R365K0.16103331
L193V195G-1.3734718
Y475R474G-1.3359435
F473R474G-1.3359435
F473R474P-0.98578442
Y475R474P-0.98578442
R365G363S-0.6921369
E361G363S-0.6921369
F473P471L-0.35229336
(MuPro1.1: Jianlin Cheng et al., Prediction of Protein Stability Changes for Single-Site Mutations Using Support Vector Machines, PROTEINS: Structure, Function, and Bioinformatics. 2006, 62:1125-1132)

Structure image for NOS3 from PDB

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Differential gene expression and gene-gene network for NOS3
Differential gene expression between mutated and non-mutated LBS samples in all 16 major cancer types

Differential co-expressed gene network based on protein-protein interaction data (CePIN)
* Left PPI network was created from samples with mutations in the LBS of NOS3 and the right PPI network was created from samples without mutations in the LBS of NOS3. Only genes with p-value < 0.05 are shown.
Red circle: input gene. Orange circle: LBSgene. Blue circle: other gene.


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Phenotype information for NOS3
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0020538Hypertension148Biomarker, GeneticVariation, Therapeutic
umls:C1956346Coronary Artery Disease109Biomarker, GeneticVariation
umls:C0007222Cardiovascular Diseases67Biomarker, GeneticVariation
umls:C0004153Atherosclerosis60AlteredExpression, Biomarker, GeneticVariation, Therapeutic
umls:C0011860Diabetes Mellitus, Type 258Biomarker, GeneticVariation
umls:C0027051Myocardial Infarction52AlteredExpression, Biomarker, GeneticVariation
umls:C0003850Arteriosclerosis49Biomarker, Therapeutic
umls:C0011881Diabetic Nephropathies30Biomarker, GeneticVariation
umls:C0085580Hypertension, Essential29Biomarker, GeneticVariation
umls:C0242350Erectile Dysfunction24Biomarker, GeneticVariation, Therapeutic
umls:C0010073Coronary Vasospasm23Biomarker, GeneticVariation
umls:C0032914Pre-Eclampsia19Biomarker, GeneticVariation
umls:C0524620Metabolic Syndrome X19Biomarker, GeneticVariation
umls:C0020542Hypertension, Pulmonary14Biomarker, GeneticVariation
umls:C0018801Heart Failure14Biomarker, GeneticVariation
umls:C0002395Alzheimer Disease13Biomarker, GeneticVariation
umls:C0151744Myocardial Ischemia13Biomarker, GeneticVariation, Therapeutic
umls:C0011854Diabetes Mellitus, Type 112Biomarker, GeneticVariation
umls:C0022116Ischemia12Biomarker, GeneticVariation, Therapeutic
umls:C0024117Pulmonary Disease, Chronic Obstructive10AlteredExpression, Biomarker, GeneticVariation
umls:C0011853Diabetes Mellitus, Experimental9Biomarker
umls:C1458155Breast Neoplasms9AlteredExpression, Biomarker, GeneticVariation
umls:C0021655Insulin Resistance7Biomarker, GeneticVariation, Therapeutic
umls:C0011875Diabetic Angiopathies6Biomarker, GeneticVariation
umls:C0004238Atrial Fibrillation6GeneticVariation, Therapeutic
umls:C0020456Hyperglycemia6Biomarker, GeneticVariation
umls:C0018800Cardiomegaly5Biomarker, GeneticVariation, Therapeutic
umls:C0035126Reperfusion Injury5AlteredExpression, Biomarker, Therapeutic
umls:C0033578Prostatic Neoplasms5Biomarker, GeneticVariation
umls:C0243026Sepsis5Biomarker, GeneticVariation
umls:C0020541Hypertension, Portal4AlteredExpression, Biomarker, Therapeutic
umls:C0340274Hypertension, Pregnancy-Induced4Biomarker, GeneticVariation
umls:C0007785Cerebral Infarction4Biomarker, GeneticVariation
umls:C0034063Pulmonary Edema3Biomarker, GeneticVariation, Therapeutic
umls:C0015934Fetal Growth Retardation3Biomarker, GeneticVariation
umls:C0020473Hyperlipidemias3Biomarker
umls:C0023893Liver Cirrhosis, Experimental3Biomarker
umls:C0027055Myocardial Reperfusion Injury3Biomarker, Therapeutic
umls:C0000832Abruptio Placentae3Biomarker, GeneticVariation
umls:C0003130Anoxia3AlteredExpression, Biomarker
umls:C0027651Neoplasms3Biomarker
umls:C0019284Hernia, Diaphragmatic2Biomarker
umls:C0020459Hyperinsulinism2Biomarker, GeneticVariation, Therapeutic
umls:C0008924Cleft Lip2Biomarker, GeneticVariation
umls:C0020545Hypertension, Renovascular2GeneticVariation, Therapeutic
umls:C0042594Vestibular Diseases1Biomarker, GeneticVariation
umls:C2609414Acute Kidney Injury1Biomarker
umls:C0001418Adenocarcinoma1Biomarker
umls:C0008925Cleft Palate1Biomarker
umls:C0520459Enterocolitis, Necrotizing1Biomarker
umls:C0014859Esophageal Neoplasms1Biomarker
umls:C0021845Intestinal Perforation1Biomarker
umls:C0038356Stomach Neoplasms1Biomarker
umls:C0038358Stomach Ulcer1Biomarker
umls:C0042514Tachycardia, Ventricular1Therapeutic
umls:C0041948Uremia1Biomarker
umls:C0151636Ventricular Premature Complexes1Therapeutic

Mutation level pathogenic information (ClinVar annotation)
Allele IDAA changeClinical significanceOriginPhenotype IDs

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Pharmacological information for NOS3
Gene expression profile of anticancer drug treated cell-lines (CCLE)
Heatmap showing the correlation between gene expression and drug response across all the cell-lines. We chose the top 20 among 138 drugs.We used Pearson's correlation coefficient.

Gene-centered drug-gene interaction network
Drug information targeting mutLBSgene (Approved drugs only)
Drug statusDrugBank IDNameTypeDrug structure
Approved|nutraceuticalDB00125L-ArginineSmall molecule
Approved|nutraceuticalDB00155L-CitrullineSmall molecule
Approved|investigationalDB00360SapropterinSmall molecule
Approved|investigational|vet_approvedDB01110MiconazoleSmall molecule
ExperimentalDB01686N,N-dimethylarginineSmall molecule
ExperimentalDB01821L-N(Omega)-Nitroarginine-2,4-L-Diaminobutyric AmideSmall molecule
ExperimentalDB01833L-2-Amino-4-(Guanidinooxy)Butyric AcidSmall molecule
ExperimentalDB019973-Bromo-7-NitroindazoleSmall molecule
ExperimentalDB02027N-{(4s)-4-Amino-5-[(2-Aminoethyl)Amino]Pentyl}-N'-NitroguanidineSmall molecule
ExperimentalDB02044N-(3-(Aminomethyl)Benzyl)AcetamidineSmall molecule
ExperimentalDB020481,2,4-Triazole-CarboxamidineSmall molecule
ExperimentalDB02077L-N(Omega)-Nitroarginine-(4r)-Amino-L-Proline AmideSmall molecule
ExperimentalDB02141S,S'-(1,4-Phenylene-Bis(1,2-Ethanediyl))Bis-IsothioureaSmall molecule
ExperimentalDB022077-NitroindazoleSmall molecule
ExperimentalDB02234EthylisothioureaSmall molecule
ExperimentalDB023352-AminothiazolineSmall molecule
ExperimentalDB02589Se-Ethyl-IsoselenoureaSmall molecule
ExperimentalDB02692(6r,1'r,2's)-5,6,7,8 TetrahydrobiopterinSmall molecule
ExperimentalDB029112,4-Diamino-6-Phenyl-5,6,7,8,-TetrahydropteridineSmall molecule
ExperimentalDB02979N1,N14-Bis((S-Methyl)Isothioureido)TetradecaneSmall molecule
ExperimentalDB02994Hydroxydimethylarsine OxideSmall molecule
ExperimentalDB030657-Nitroindazole-2-CarboxamidineSmall molecule
ExperimentalDB031006-NitroindazoleSmall molecule
ExperimentalDB03144N-Omega-Hydroxy-L-ArginineSmall molecule
ExperimentalDB03305N5-Iminoethyl-L-OrnithineSmall molecule
ExperimentalDB033325,6-Cyclic-TetrahydropteridineSmall molecule
ExperimentalDB03707S-Ethyl-N-Phenyl-IsothioureaSmall molecule
ExperimentalDB03910S,S'-(1,3-Phenylene-Bis(1,2-Ethanediyl))Bis-IsothioureaSmall molecule
ExperimentalDB039186s-5,6,7,8-TetrahydrobiopterinSmall molecule
ExperimentalDB03963S-(Dimethylarsenic)CysteineSmall molecule
ExperimentalDB03974L-HomoarginineSmall molecule
ExperimentalDB04018S-Isopropyl-IsothioureaSmall molecule
ExperimentalDB04223NitroarginineSmall molecule
ExperimentalDB045345-NitroindazoleSmall molecule
ExperimentalDB04559N-(Chlorophenyl)-N'-HydroxyguanidineSmall molecule
Approved|investigationalDB05676ApremilastSmall molecule
ExperimentalDB07001(3S,5E)-3-propyl-3,4-dihydrothieno[2,3-f][1,4]oxazepin-5(2H)-imineSmall molecule
ExperimentalDB072445-{4-[(3,5-DIFLUOROBENZYL)AMINO]PHENYL}-6-ETHYLPYRIMIDINE-2,4-DIAMINESmall molecule
ExperimentalDB07388ETHYL 4-[(4-METHYLPYRIDIN-2-YL)AMINO]PIPERIDINE-1-CARBOXYLATESmall molecule
ExperimentalDB08018N-{(3S,4S)-4-[(6-AMINO-4-METHYLPYRIDIN-2-YL)METHYL]PYRROLIDIN-3-YL}-N'-(4-CHLOROBENZYL)ETHANE-1,2-DIAMINESmall molecule
ExperimentalDB08019N-{(3R,4S)-4-[(6-amino-4-methylpyridin-2-yl)methyl]pyrrolidin-3-yl}-N'-(3-chlorobenzyl)ethane-1,2-diamineSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of NOS3 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
CLWCHLORZOXAZONE1m9jAE361
CLWCHLORZOXAZONE1m9jBE361
7NI7-NITROINDAZOLE1m9kAE361
7NI7-NITROINDAZOLE1m9kBE361
6NI6-NITROINDAZOLE1m9mAE361
6NI6-NITROINDAZOLE1m9mBE361
5NI5-NITROINDAZOLE1m9qAE361
5NI5-NITROINDAZOLE1m9qBE361
INE3-BROMO-7-NITROINDAZOLE1m9rAE361
INE3-BROMO-7-NITROINDAZOLE1m9rBE361
HARN(5)-[(HYDROXYAMINO)(IMINO)METHYL]-L-ORNITHINE3nosAE361
HARN(5)-[(HYDROXYAMINO)(IMINO)METHYL]-L-ORNITHINE3nosBE361
ARGARGININE4d1oAE361
ARGARGININE4d1oBE361
Q166-((((3S, 5R)-5-(((6-AMINO-4-METHYLPYRIDIN-2- YL)METHOXY)METHYL)PYRROLIDIN-3-YL)OXY)METHYL) -4-METHYLPYRIDIN-2-AMINE4d1pAE361
Q166-((((3S, 5R)-5-(((6-AMINO-4-METHYLPYRIDIN-2- YL)METHOXY)METHYL)PYRROLIDIN-3-YL)OXY)METHYL) -4-METHYLPYRIDIN-2-AMINE4d1pBE361
HEMHEME B1m9jAE361 F473 Y475
HEMHEME B1m9jBE361 F473 Y475
HEMHEME B1m9kAE361 F473 Y475
HEMHEME B1m9kBE361 F473 Y475
HEMHEME B1m9mAE361 F473 Y475
HEMHEME B1m9mBE361 F473 Y475
HEMHEME B1m9qAE361 F473 Y475
HEMHEME B1m9qBE361 F473 Y475
HEMHEME B1m9rAE361 F473 Y475
HEMHEME B1m9rBE361 F473 Y475
HEMHEME B4d1oAE361 F473 Y475
HEMHEME B4d1oBE361 F473 Y475
HEMHEME B4d1pAE361 F473 Y475
HEMHEME B4d1pBE361 F473 Y475
HEMHEME B3nosAL193 E361 F473 Y475
HEMHEME B3nosBL193 E361 F473 Y475
INE3-BROMO-7-NITROINDAZOLE1m9rAR365
INE3-BROMO-7-NITROINDAZOLE1m9rBR365
H4B5,6,7,8-TETRAHYDROBIOPTERIN3nosAR365
H4B5,6,7,8-TETRAHYDROBIOPTERIN3nosBR365
H4B5,6,7,8-TETRAHYDROBIOPTERIN4d1oAR365
H4B5,6,7,8-TETRAHYDROBIOPTERIN4d1oBR365
H4B5,6,7,8-TETRAHYDROBIOPTERIN4d1pAR365
H4B5,6,7,8-TETRAHYDROBIOPTERIN4d1pBR365


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Conservation information for LBS of NOS3
Multiple alignments for P29474 in multiple species
LBSAA sequence# speciesSpecies
A181QAWRNAPRCVG3Homo sapiens, Mus musculus, Rattus norvegicus
C184RNAPRCVGRIQ3Homo sapiens, Mus musculus, Rattus norvegicus
E361WYMSSEIGMRD2Mus musculus, Rattus norvegicus
E361WYMSTEIGTRN1Homo sapiens
F353FPAAPFSGWYM3Homo sapiens, Mus musculus, Rattus norvegicus
F473FLSPAFRYQPD3Homo sapiens, Mus musculus, Rattus norvegicus
G186APRCVGRIQWG3Homo sapiens, Mus musculus, Rattus norvegicus
G355AAPFSGWYMSS2Mus musculus, Rattus norvegicus
G355AAPFSGWYMST1Homo sapiens
L193IQWGKLQVFDA3Homo sapiens, Mus musculus, Rattus norvegicus
M339PAVSNMLLEIG3Homo sapiens, Mus musculus, Rattus norvegicus
M358FSGWYMSSEIG2Mus musculus, Rattus norvegicus
M358FSGWYMSTEIG1Homo sapiens
N366EIGMRDLCDPH2Mus musculus, Rattus norvegicus
N366EIGTRNLCDPH1Homo sapiens
P334RWYALPAVSNM3Homo sapiens, Mus musculus, Rattus norvegicus
Q189CVGRIQWGKLQ3Homo sapiens, Mus musculus, Rattus norvegicus
Q247RIWNSQLVRYA2Homo sapiens, Rattus norvegicus
Q247RIWNSQLIRYA1Mus musculus
R183WRNAPRCVGRI3Homo sapiens, Mus musculus, Rattus norvegicus
R250NSQLVRYAGYR2Homo sapiens, Rattus norvegicus
R250NSQLIRYAGYR1Mus musculus
R365SEIGMRDLCDP2Mus musculus, Rattus norvegicus
R365TEIGTRNLCDP1Homo sapiens
S102RRCLGSLVFPR3Homo sapiens, Mus musculus, Rattus norvegicus
S226RGNLRSAITVF3Homo sapiens, Mus musculus, Rattus norvegicus
S354PAAPFSGWYMS3Homo sapiens, Mus musculus, Rattus norvegicus
V185NAPRCVGRIQW3Homo sapiens, Mus musculus, Rattus norvegicus
V336YALPAVSNMLL3Homo sapiens, Mus musculus, Rattus norvegicus
W178GAKQAWRNAPR3Homo sapiens, Mus musculus, Rattus norvegicus
W356APFSGWYMSSE2Mus musculus, Rattus norvegicus
W356APFSGWYMSTE1Homo sapiens
W447PADWAWIVPPI3Homo sapiens, Mus musculus, Rattus norvegicus
Y331LGLRWYALPAV3Homo sapiens, Mus musculus, Rattus norvegicus
Y357PFSGWYMSSEI2Mus musculus, Rattus norvegicus
Y357PFSGWYMSTEI1Homo sapiens
Y475SPAFRYQPDPW3Homo sapiens, Mus musculus, Rattus norvegicus


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