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 NR3C1
Gene summary
Basic gene Info.Gene symbolNR3C1
Gene namenuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)
SynonymsGCCR|GCR|GCRST|GR|GRL
CytomapUCSC genome browser: 5q31.3
Type of geneprotein-coding
RefGenesNM_000176.2,
NM_001018074.1,NM_001018075.1,NM_001018076.1,NM_001018077.1,
NM_001020825.1,NM_001024094.1,NM_001204258.1,NM_001204259.1,
NM_001204260.1,NM_001204261.1,NM_001204262.1,NM_001204263.1,
NM_001204264.1,NM_001204265.1,
Descriptionglucocorticoid nuclear receptor variant 1glucocorticoid receptor
Modification date20141222
dbXrefs MIM : 138040
HGNC : HGNC
Ensembl : ENSG00000113580
HPRD : 00679
Vega : OTTHUMG00000129677
ProteinUniProt: P04150
go to UniProt's Cross Reference DB Table
ExpressionCleanEX: HS_NR3C1
BioGPS: 2908
PathwayNCI Pathway Interaction Database: NR3C1
KEGG: NR3C1
REACTOME: NR3C1
Pathway Commons: NR3C1
ContextiHOP: NR3C1
ligand binding site mutation search in PubMed: NR3C1
UCL Cancer Institute: NR3C1
Assigned class in mutLBSgeneDBA: This gene has a literature evidence and it belongs to targetable_mutLBSgenes.
References showing study about ligand binding site mutation for NR3C1.1. Murani, E., Reyer, H., Ponsuksili, S., Fritschka, S., & Wimmers, K. (2012). A substitution in the ligand binding domain of the porcine glucocorticoid receptor affects activity of the adrenal gland. PloS one, 7(9), e45518. 23029068
2. Donner, K. M., Hiltunen, T. P., Jänne, O. A., Sane, T., & Kontula, K. (2013). Generalized glucocorticoid resistance caused by a novel two-nucleotide deletion in the hormone-binding domain of the glucocorticoid receptor gene NR3C1. European Journal of Endocrinology, 168(1), K9-K18. 23076843
3. Nicolaides, N. C., Geer, E. B., Vlachakis, D., Roberts, M. L., Psarra, A. M. G., Moutsatsou, P., ... & Charmandari, E. (2015). A novel mutation of the hGR gene causing Chrousos syndrome. European journal of clinical investigation, 45(8), 782-791. 26031419

Gene ontology having evidence of Inferred from Direct Assay (IDA) from Entrez
GO IDGO TermPubMed ID
GO:0006355regulation of transcription, DNA-templated19141540
GO:0045944positive regulation of transcription from RNA polymerase II promoter15769988
GO:0071383cellular response to steroid hormone stimulus15769988


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Ligand binding site mutations for NR3C1

Cancer type specific mutLBS sorted by frequency
LBSAAchange of nsSNVCancer type# samples
L563T562MBRCA1
M604M604ICOAD1
K667T668PHNSC1
M604M604IOV1
V443V443ASTAD1
L732N731TSTAD1
K471C473FSTAD1
Q570,G568R569WUCEC1
E751E751KUCEC1
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 NR3C1
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
V443V443A-1.2132477
L732N731T-0.84845558
K471C473F-0.66889044
Q570R569W-0.56036191
G568R569W-0.56036191
L563T562M-0.54793956
K667T668P-0.52749314
E751E751K-0.30421375
M604M604I-0.29178897
(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 NR3C1 from PDB

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Differential gene expression and gene-gene network for NR3C1
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 NR3C1 and the right PPI network was created from samples without mutations in the LBS of NR3C1. 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 NR3C1
Gene level disease information (DisGeNet)
Disease IDDisease name# PubMedAssociation type
umls:C0011581Depressive Disorder25Biomarker
umls:C0005586Bipolar Disorder17AlteredExpression, Biomarker, GeneticVariation
umls:C0020538Hypertension14Biomarker, GeneticVariation
umls:C0036341Schizophrenia11AlteredExpression, Biomarker, GeneticVariation
umls:C0028840Ocular Hypertension2Biomarker, GeneticVariation
umls:C0014175Endometriosis2Biomarker
umls:C0600260Lung Diseases, Obstructive2Biomarker
umls:C0033578Prostatic Neoplasms2Biomarker
umls:C0033975Psychotic Disorders2Biomarker
umls:C0236736Cocaine-Related Disorders2Biomarker
umls:C293640346, XX Disorders of Sex Development1Biomarker
umls:C0020621Hypokalemia1Biomarker

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

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Pharmacological information for NR3C1
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|investigationalDB00180FlunisolideSmall molecule
ApprovedDB00223DiflorasoneSmall molecule
ApprovedDB00240AlclometasoneSmall molecule
ApprovedDB00253MedrysoneSmall molecule
ApprovedDB00288AmcinonideSmall molecule
ApprovedDB00324FluorometholoneSmall molecule
Approved|vet_approvedDB00351Megestrol acetateSmall molecule
Approved|investigationalDB00394Beclomethasone dipropionateSmall molecule
ApprovedDB00421SpironolactoneSmall molecule
Approved|vet_approvedDB00443BetamethasoneSmall molecule
ApprovedDB00547DesoximetasoneSmall molecule
ApprovedDB00588Fluticasone PropionateSmall molecule
Approved|investigational|vet_approvedDB00591Fluocinolone AcetonideSmall molecule
ApprovedDB00596UlobetasolSmall molecule
Approved|vet_approvedDB00620TriamcinoloneSmall molecule
Approved|vet_approvedDB00635PrednisoneSmall molecule
Approved|vet_approvedDB00663FlumethasoneSmall molecule
ApprovedDB00687FludrocortisoneSmall molecule
Approved|vet_approvedDB00741HydrocortisoneSmall molecule
Approved|vet_approvedDB00764MometasoneSmall molecule
ApprovedDB00769HydrocortamateSmall molecule
Approved|investigationalDB00834MifepristoneSmall molecule
ApprovedDB00838ClocortoloneSmall molecule
ApprovedDB00846FlurandrenolideSmall molecule
Approved|vet_approvedDB00860PrednisoloneSmall molecule
ApprovedDB00873LoteprednolSmall molecule
ApprovedDB00896RimexoloneSmall molecule
Approved|vet_approvedDB00959MethylprednisoloneSmall molecule
ApprovedDB01013Clobetasol propionateSmall molecule
Approved|investigationalDB01047FluocinonideSmall molecule
ApprovedDB01130PrednicarbateSmall molecule
Approved|illicitDB01185FluoxymesteroneSmall molecule
ApprovedDB01222BudesonideSmall molecule
Approved|investigational|vet_approvedDB01234DexamethasoneSmall molecule
Approved|investigationalDB01260DesonideSmall molecule
ApprovedDB01380Cortisone acetateSmall molecule
ApprovedDB01384ParamethasoneSmall molecule
Approved|investigationalDB01410CiclesonideSmall molecule
ExperimentalDB02210Hexane-1,6-DiolSmall molecule
InvestigationalDB05423ORG-34517Small molecule
ApprovedDB06781DifluprednateSmall molecule
ApprovedDB08867UlipristalSmall molecule
ApprovedDB08906Fluticasone furoateSmall molecule

Gene-centered ligand-gene interaction network

Ligands binding to mutated ligand binding site of NR3C1 go to BioLip
Ligand IDLigand short nameLigand long namePDB IDPDB namemutLBS
IIIPeptide ligand (PRO,VAL,SER,PRO,LYS,LYS,LYS,GLU,ASN,ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP,LYS,ASP,ASP,THR)1m2zDE751
IIIPeptide ligand (GLN,LYS,SER,LEU,LEU,GLN,GLN,LEU,LEU,THR,GLU)3bqdAE751
IIIPeptide ligand (ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP,LYS)3k23AE751
IIIPeptide ligand (ASN,ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP,LYS)3k23BE751
IIIPeptide ligand (GLU,ASN,ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP)3k23CE751
IIIPeptide ligand (GLU,ASN,ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP,LYS,ASP,ASP)4csjAE751
IIIPeptide ligand (GLU,ASN,ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP,LYS,ASP,ASP)4udcAE751
IIIPeptide ligand (GLU,ASN,ALA,LEU,LEU,ARG,TYR,LEU,LEU,ASP,LYS,ASP,ASP)4uddAE751
NUCNucleic Acids4hn5BK471
NUCNucleic Acids4hn6BK471
NUCNucleic Acids5cc1AK471
NUCNucleic Acids5cc1WK471
JZRHEXYL BETA-D-GLUCOPYRANOSIDE3k22AL563
JZRHEXYL BETA-D-GLUCOPYRANOSIDE3k22BL563
486MIFEPRISTONE3h52BL563 G568 Q570 M604 L732
486MIFEPRISTONE3h52AL563 Q570 L732
DEXDEXAMETHASONE1m2zAL563 Q570 M604
DEXDEXAMETHASONE1m2zDL563 Q570 M604
DEXDEXAMETHASONE1p93AL563 Q570 M604
DEXDEXAMETHASONE1p93BL563 Q570 M604
DEXDEXAMETHASONE1p93DL563 Q570 M604
8665-AMINO-N-[(2S)-2-({[(2,6-DICHLOROPHENYL)CARBONYL](ETHYL)AMINO}METHYL)-3,3,3-TRIFLUORO-2-HYDROXYPROPYL]-1-(4-FLUOROPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE3e7cAL563 Q570 M604
8665-AMINO-N-[(2S)-2-({[(2,6-DICHLOROPHENYL)CARBONYL](ETHYL)AMINO}METHYL)-3,3,3-TRIFLUORO-2-HYDROXYPROPYL]-1-(4-FLUOROPHENYL)-1H-PYRAZOLE-4-CARBOXAMIDE3e7cBL563 Q570 M604
486MIFEPRISTONE3h52CL563 Q570 M604
JZSN-[(1R)-2-AMINO-1-METHYL-2-OXOETHYL]-3-(6-METHYL-4-{[3,3,3-TRIFLUORO-2-HYDROXY-2-(TRIFLUOROMETHYL)PROPYL]AMINO}-1H-INDAZOL-1-YL)BENZAMIDE3k22AL563 Q570 M604
JZSN-[(1R)-2-AMINO-1-METHYL-2-OXOETHYL]-3-(6-METHYL-4-{[3,3,3-TRIFLUORO-2-HYDROXY-2-(TRIFLUOROMETHYL)PROPYL]AMINO}-1H-INDAZOL-1-YL)BENZAMIDE3k22BL563 Q570 M604
JZN1-{[3-(4-{[(2R)-4-(5-FLUORO-2-METHOXYPHENYL)-2-HYDROXY-4-METHYL-2-(TRIFLUOROMETHYL)PENTYL]AMINO}-6-METHYL-1H-INDAZOL-1-YL)PHENYL]CARBONYL}-D-PROLINAMIDE3k23AL563 Q570 M604
MOFMOMETASONE FUROATE4p6wAL563 Q570 M604
HCY(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE4p6xAL563 Q570 M604
HCY(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE4p6xCL563 Q570 M604
HCY(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE4p6xEL563 Q570 M604
HCY(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE4p6xGL563 Q570 M604
HCY(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE4p6xIL563 Q570 M604
HCY(11ALPHA,14BETA)-11,17,21-TRIHYDROXYPREGN-4-ENE-3,20-DIONE4p6xKL563 Q570 M604
DEXDEXAMETHASONE4udcAL563 Q570 M604
CV7DESISOBUYTYRYL CICLESONIDE4uddAL563 Q570 M604
JZN1-{[3-(4-{[(2R)-4-(5-FLUORO-2-METHOXYPHENYL)-2-HYDROXY-4-METHYL-2-(TRIFLUOROMETHYL)PENTYL]AMINO}-6-METHYL-1H-INDAZOL-1-YL)PHENYL]CARBONYL}-D-PROLINAMIDE3k23BL563 Q570 M604 K667 L732
486MIFEPRISTONE1nhzAL563 Q570 M604 L732
DEXDEXAMETHASONE1p93CL563 Q570 M604 L732
DAYDEACYLCORTIVAZOL3bqdAL563 Q570 M604 L732
GW6VERAMYST3cldAL563 Q570 M604 L732
GW6VERAMYST3cldBL563 Q570 M604 L732
486MIFEPRISTONE3h52DL563 Q570 M604 L732
JZN1-{[3-(4-{[(2R)-4-(5-FLUORO-2-METHOXYPHENYL)-2-HYDROXY-4-METHYL-2-(TRIFLUOROMETHYL)PENTYL]AMINO}-6-METHYL-1H-INDAZOL-1-YL)PHENYL]CARBONYL}-D-PROLINAMIDE3k23CL563 Q570 M604 L732
LSJN-{3-[(1Z)-1-(10-METHOXYDIBENZO[B,E]OXEPIN-11(6H)- YLIDENE)PROPYL]PHENYL}METHANESULFONAMIDE4lsjAL563 Q570 M604 L732
NN7N-[(2S)-1-[[1-(4-FLUOROPHENYL)INDAZOL-4-YL] AMINO]PROPAN-2-YL]-2,4,6-TRIMETHYL- BENZENESULFONAMIDE4csjAL563 Q570 M604 L732
NUCNucleic Acids4hn5AV443 K471
NUCNucleic Acids4hn6AV443 K471


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Conservation information for LBS of NR3C1
Multiple alignments for P04150 in multiple species
LBSAA sequence# speciesSpecies


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