Nomenclature: Glucocorticoid receptor

Systematic Nomenclature: NR3C1

Family: 3C. 3-Ketosteroid receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates. 

Contents

Gene and Protein Information
Species AA Chromosomal Location Gene Symbol Gene Name Reference
Human 778 5q31-q32 NR3C1 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) 21
Mouse 792 18 20.0 cM Nr3c1 nuclear receptor subfamily 3, group C, member 1 15
Rat 794 18p12 Nr3c1 nuclear receptor subfamily 3, group C, member 1 34
Previous and Unofficial Names
GR
GCCR
GCR
GRL
Glucocorticoid
Type II glucocorticoid receptor
nuclear receptor subfamily 3, group C, member 1
glucocorticoid receptor
Grl-1
Grl1
Database Links
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
NURSA Receptor
OMIM
Orphanet Gene
PharmGKB Gene
PhosphoSitePlus
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Glucocorticoid receptor- ligand binding domain (bound to an agonist)
PDB Id:  1P93
Ligand:  dexamethasone
Resolution:  2.7Å
Species:  Human
References:  28
Natural/Endogenous Ligands
aldosterone
corticosterone
cortisol
deoxycortisone
Comments: cortisol and corticosterone are the principal endogenous agonists
Rank order of potency (Human)
cortisol, corticosterone >> aldosterone, deoxycortisone  [46]
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
clobetasol propionate Hs Agonist 9.18 pKi 1
pKi 9.18 (Ki 6.62x10-10 M) [1]
desoximetasone Hs Agonist 8.93 pKi 1
pKi 8.93 (Ki 1.17x10-9 M) [1]
fluorometholone Hs Agonist 8.8 pKi 1
pKi 8.8 (Ki 1.58x10-9 M) [1]
flunisolide Hs Agonist 8.62 pKi 1
pKi 8.62 (Ki 2.42x10-9 M) [1]
diflorasone diacetate Hs Agonist 8.54 pKi 1
pKi 8.54 (Ki 2.91x10-9 M) [1]
beclometasone Hs Full agonist 8.43 pKi 1
pKi 8.43 (Ki 3.74x10-9 M) [1]
methylprednisolone Hs Agonist 8.3 pKi 1
pKi 8.3 (Ki 5.03x10-9 M) [1]
ciclesonide Hs Agonist 7.43 pKi 3
pKi 7.43 (Ki 3.7x10-8 M) [3]
prednisone Hs Agonist 6.28 pKi 1
pKi 6.28 (Ki 5.21x10-7 M) [1]
budesonide Hs Agonist 7.91 pEC50 35
pEC50 7.91 (EC50 1.24x10-8 M) [35]
dexamethasone Hs Agonist 8.1 – 9.0 pIC50 20,32,46
pIC50 8.1 – 9.0 [20,32,46]
fluocinolone acetonide Hs Agonist 8.5 pIC50 1
pIC50 8.5 (IC50 3.13x10-9 M) [1]
fluocinonide Hs Agonist 8.28 pIC50 1
pIC50 8.28 (IC50 5.26x10-9 M) [1]
triamcinolone acetonide Hs Agonist 8.2 pIC50 17,58
pIC50 8.2 [17,58]
betamethasone Hs Full agonist 8.11 pIC50 1
pIC50 8.11 (IC50 7.74x10-9 M) [1]
prednisolone Hs Agonist 7.8 pIC50 32
pIC50 7.8 [32]
triamcinolone Hs Agonist 7.7 pIC50 32
pIC50 7.7 [32]
cortisol Hs Agonist 7.3 – 8.0 pIC50 20,32,46
pIC50 7.3 – 8.0 [20,32,46]
corticosterone Mm Agonist 7.2 pIC50 20,32,46
pIC50 7.2 [20,32,46]
deoxycorticosterone Hs Agonist 7.2 pIC50 32,46
pIC50 7.2 [32,46]
[3H]dexamethasone Hs Agonist - -
RU26988 ? Agonist - -
fluticasone Hs Agonist - -
difluprednate Hs Agonist - - 50
[50]
RU28362 Hs Agonist - -
View species-specific agonist tables
Agonist Comments
Cortisol is the main glucocorticoid in humans whereas corticosterone is the main form in rodents. Dexamethasone, cortisol and deoxycorticosterone all have high affinity for mineralocorticoid receptors as well.
Note that for ciclesonide, the affinity appears low. However, this is because ciclesonide is a prodrug. The active metabolite, desisobutyrylciclesonide, has a higher affinity of 0.31nM (Ki) [3].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
mifepristone Hs Antagonist 9.4 pKd 19,46
pKd 9.4 [19,46]
fluticasone propionate Hs Antagonist 9.3 pIC50 4
pIC50 9.3 (IC50 5x10-10 M) [4]
Description: Inhibition of [3H]dexamethasone binding to recombinant human glucocorticoid receptor ecpressed in Tni cells.
onapristone Hs Antagonist - -
ZK112993 Hs Antagonist - -
DNA Binding
Structure:  Homodimer, Heterodimer, RXR partner
HRE core sequence:  GGTACANNNTGTTCT
Response element:  GRE, Half site, Palindrome
Co-binding Partners
Name Interaction Effect Reference
Retinoid X receptor-α Physical, Functional DNA binding
HMGD Physical, Functional DNA binding 5,53
AP1 Physical, Functional transactivation 25,48,57
NF-κB Physical, Functional transactivation 8,47
14-3-3ρ Physical, Functional cellular localization, transactivation 29
HSP90 Physical, Functional Cellular localization 41-43
Main Co-regulators
Name Activity Specific Ligand dependent AF-2 dependent Comments References
CREBBP Co-activator No Yes Yes Histone acetyltransferase, a transcriptional cointegrator 26
NCOA2 Co-activator No Yes Yes 22,52,54
PTMS Co-activator Yes Yes No Has little effect on ER-mediated transactivation. 40
NCOA6 Co-activator No Yes Yes Likely a member of multimeric complex including NIF-1. 31
MED1 Co-activator No Yes Yes 44
BAG1 Co-repressor No No Yes A regulator of HSP70 and a co-repressor. 30
Main Target Genes
Name Species Effect Technique Comments References
PCK1 Human Both ChIP, Transient transfection 9
Interleukin 8 Human Repressed 51
Dusp1 Mouse Activated Transient transfection Dusp1 is also known as MAP kinase phosphatase-1 (MKP-1) 27
annexin A1 Human Activated Transient transfection, other Also known as Lipocrotin-1 36,45
TNF Human Repressed 55
Tissue Distribution
Ubiquitous
Species:  Human
Technique:  Northern, Q-PCR, in situ, Western, immunohistology, other
References:  10,21,33,38-39
Tissue Distribution Comments
GR is expressed ubiquitously in mammals.
Functional Assays
Hyperglycemic effect
Species:  Human
Tissue:  Serum
Response measured:  Blood glucose level is elevated by intravenous injection of glucocorticoids.
References:  49,56
Thymocyte-killing effects.
Species:  Rat
Tissue:  Thymus
Response measured:  Thymus weight. Thymocytes undergo apoptosis in a GR-dependent manner.
References:  11
Dexmethasone suppression.
Species:  Human
Tissue:  Urine, saliva
Response measured:  Endogenous cortisol level is suppressed significantly by exogenous dexamethasone via GR and the hypothalamus-pituitary-adrenal axis.
References:  24
Physiological Consequences of Altering Gene Expression
GR -/- mice:- not viable (die a few hours after birth due to respiratory failure).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells
References:  12-13
Disruption of hypothalamic-pituitary-adrenocortical system in transgenic mice expressing type II glucocorticoid receptor antisense ribonucleic acid permanently impairs T cell function.
Species:  Mouse
Tissue:  Hypothalamic-pituitary-adrenocortical system
Technique:  Antisense olignucleotide
References:  37
Physiological Consequences of Altering Gene Expression Comments
GR -/- mice also present the following at birth:- lungs at birth are severely atelectatic, and development is impaired from day 15.5 p.c. Newborn livers have a reduced capacity to activate genes for key gluconeogenic enzymes. Feedback regulation via the hypothalamic-pituitary-adrenal axis is severely impaired resulting in elevated levels of plasma adrenocorticotrophic hormone (15-fold) and plasma corticosterone (2.5-fold). Accordingly, adrenal glands are enlarged because of hypertrophy of the cortex, resulting in increased expression of key cortical steroid biosynthetic enzymes, such as side-chain cleavage enzyme, steroid 11 β-hydroxylase, and aldosterone synthase. Adrenal glands lack a central medulla and synthesize no adrenaline. They contain no adrenergic chromaffin cells and only scattered noradrenergic chromaffin cells even when analyzed from the earliest stages of medulla development.
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0000013 abnormal adipose tissue distribution PMID: 10471508 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0008504 abnormal adrenal chromaffin cell morphology PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0008504 abnormal adrenal chromaffin cell morphology PMID: 10357937 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0008504 abnormal adrenal chromaffin cell morphology PMID: 10357937 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0008288 abnormal adrenal cortex morphology PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0000639 abnormal adrenal gland morphology PMID: 7628695 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0000639 abnormal adrenal gland morphology PMID: 18697839 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0003962 abnormal adrenaline level PMID: 7628695 
Nr3c1tm2Gsc|Tg(Drd1a-cre)AGsc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Drd1a-cre)AGsc/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
MGI:3761815  MGI:95824  MP:0009748 abnormal behavioral response to addictive substance PMID: 19234455 
Nr3c1+|Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1+
B6.129P2-Nr3c1
MGI:95824  MP:0005167 abnormal blood-brain barrier function PMID: 18523311 
Nr3c1tm2Gsc|Tg(Runx2-icre)1Jtuc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Runx2-icre)1Jtuc/0
involves: 129P2/OlaHsd * FVB/N
MGI:4455014  MGI:95824  MP:0010119 abnormal bone mineral density PMID: 20519123 
Nr3c1tm2Gsc|Tg(Runx2-icre)1Jtuc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Runx2-icre)1Jtuc/0
involves: 129P2/OlaHsd * FVB/N
MGI:4455014  MGI:95824  MP:0008271 abnormal bone ossification PMID: 20519123 
Nr3c1tm2Gsc|Tg(Runx2-icre)1Jtuc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Runx2-icre)1Jtuc/0
involves: 129P2/OlaHsd * FVB/N
MGI:4455014  MGI:95824  MP:0000130 abnormal cancellous bone morphology PMID: 20519123 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0000494 abnormal cecum morphology PMID: 12949501 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0005345 abnormal circulating corticosterone level PMID: 18697839 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0002065 abnormal fear/anxiety-related behavior PMID: 10471508 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0008750 abnormal interferon level PMID: 12949501 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0008751 abnormal interleukin level PMID: 12949501 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0000609 abnormal liver physiology PMID: 7628695 
Nr3c1tm1Ljm Nr3c1tm1Ljm/Nr3c1tm1Ljm
involves: 129S6/SvEvTac * C57BL/6
MGI:95824  MP:0001176 abnormal lung development PMID: 12165507 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001176 abnormal lung development PMID: 7628695 
Nr3c1tm1Ljm Nr3c1tm1Ljm/Nr3c1tm1Ljm
involves: 129S6/SvEvTac * C57BL/6
MGI:95824  MP:0001175 abnormal lung morphology PMID: 12165507 
Nr3c1tm2Gsc|Tg(Wap-cre)1Gsc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Wap-cre)1Gsc/0
involves: 129P2/OlaHsd * FVB/N
MGI:3527253  MGI:95824  MP:0009506 abnormal mammary gland alveolus morphology PMID: 15471946 
Nr3c1tm2Gsc|Tg(Wap-cre)1Gsc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Wap-cre)1Gsc/0
involves: 129P2/OlaHsd * FVB/N
MGI:3527253  MGI:95824  MP:0006269 abnormal mammary gland growth during pregnancy PMID: 15471946 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6 * SJL
MGI:2176172  MGI:95824  MP:0002272 abnormal nervous system electrophysiology PMID: 19234455 
Nr3c1tm2Gsc|Tg(Drd1a-cre)AGsc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Drd1a-cre)AGsc/0
involves: 129P2/OlaHsd * C57BL/6 * FVB/N
MGI:3761815  MGI:95824  MP:0002272 abnormal nervous system electrophysiology PMID: 19234455 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0003964 abnormal noradrenaline level PMID: 7628695 
Nr3c1tm2Gsc|Tg(Runx2-icre)1Jtuc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Runx2-icre)1Jtuc/0
involves: 129P2/OlaHsd * FVB/N
MGI:4455014  MGI:95824  MP:0008395 abnormal osteoblast differentiation PMID: 20519123 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd * 129X1/SvJ
MGI:95824  MP:0008395 abnormal osteoblast differentiation PMID: 20519123 
Nr3c1tm3Gsc Nr3c1tm3Gsc/Nr3c1tm3Gsc
involves: 129P2/OlaHsd * FVB/N
MGI:95824  MP:0005006 abnormal osteoblast physiology PMID: 20519123 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd * 129X1/SvJ
MGI:95824  MP:0005006 abnormal osteoblast physiology PMID: 20519123 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008872 abnormal physiological response to xenobiotic PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008872 abnormal physiological response to xenobiotic PMID: 19017639 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0003115 abnormal respiratory system development PMID: 7628695 
Nr3c1tm1Ljm Nr3c1tm1Ljm/Nr3c1tm1Ljm
involves: 129S6/SvEvTac * C57BL/6
MGI:95824  MP:0009258 abnormal thymocyte apoptosis PMID: 12165507 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0003118 abnormal tracheal-bronchial branching morphogenesis PMID: 7628695 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0008752 abnormal tumor necrosis factor level PMID: 12949501 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0008294 abnormal zona fasciculata morphology PMID: 7628695 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0008294 abnormal zona fasciculata morphology PMID: 18697839 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008294 abnormal zona fasciculata morphology PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008294 abnormal zona fasciculata morphology PMID: 19017639 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0008293 abnormal zona glomerulosa morphology PMID: 18697839 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0008295 abnormal zona reticularis morphology PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0000643 absent adrenal medulla PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0000645 absent adrenergic chromaffin cells PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0001742 absent circulating adrenaline PMID: 10357937 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0001742 absent circulating adrenaline PMID: 10357937 
Nr3c1tm2Ljm|Tg(Camk2a-cre)T50Stl Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Camk2a-cre)T50Stl/?
involves: 129 * BALB/c * C57BL/6 * CBA
MGI:3531298  MGI:95824  MP:0001899 absent long term depression PMID: 15623560 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001177 atelectasis PMID: 7628695 
Nr3c1tm2Ljm|Tg(Camk2a-cre)T50Stl Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Camk2a-cre)T50Stl/?
involves: 129 * BALB/c * C57BL/6 * CBA
MGI:3531298  MGI:95824  MP:0002573 behavioral despair PMID: 15623560 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0009481 cecum inflammation PMID: 12949501 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001575 cyanosis PMID: 7628695 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0001364 decreased anxiety-related response PMID: 10471508 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0005017 decreased B cell number PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0005017 decreased B cell number PMID: 19017639 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0001258 decreased body length PMID: 10471508 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0001265 decreased body size PMID: 10471508 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0001262 decreased body weight PMID: 10471508 
Nr3c1tm2Gsc|Tg(Runx2-icre)1Jtuc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Runx2-icre)1Jtuc/0
involves: 129P2/OlaHsd * FVB/N
MGI:4455014  MGI:95824  MP:0000063 decreased bone density PMID: 20519123 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0010121 decreased bone mineral density PMID: 10471508 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008075 decreased CD4-positive T cell number PMID: 19017639 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008079 decreased CD8-positive T cell number PMID: 19017639 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0002664 decreased circulating adrenocorticotropin level PMID: 10471508 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002664 decreased circulating adrenocorticotropin level PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002664 decreased circulating adrenocorticotropin level PMID: 19017639 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002665 decreased circulating corticosterone level PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002665 decreased circulating corticosterone level PMID: 19017639 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0005664 decreased circulating noradrenaline level PMID: 10357937 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0005664 decreased circulating noradrenaline level PMID: 10357937 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002780 decreased circulating testosterone level PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002780 decreased circulating testosterone level PMID: 19017639 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0008973 decreased erythroid progenitor cell number PMID: 10580006 
Nr3c1tm3Gsc Nr3c1tm3Gsc/Nr3c1tm3Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0008973 decreased erythroid progenitor cell number PMID: 10580006 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0003884 decreased macrophage cell number PMID: 19017639 
Nr3c1tm2Gsc|Tg(Lck-cre)I57Jxm Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Lck-cre)I57Jxm/0
B6.Cg-Nr3c1 Tg(Lck-cre)I57Jxm
MGI:2177579  MGI:95824  MP:0008874 decreased physiological sensitivity to xenobiotic PMID: 18523311 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0008770 decreased survivor rate PMID: 10357937  12495930 
Nr3c1+|Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1+
B6.129P2-Nr3c1
MGI:95824  MP:0006414 decreased T cell apoptosis PMID: 16424199 
Nr3c1tm2Gsc|Tg(Lck-cre)I57Jxm Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Lck-cre)I57Jxm/0
B6.Cg-Nr3c1 Tg(Lck-cre)I57Jxm
MGI:2177579  MGI:95824  MP:0006414 decreased T cell apoptosis PMID: 18523311 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0000642 enlarged adrenal glands PMID: 7628695 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0000642 enlarged adrenal glands PMID: 18697839 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0008292 enlarged adrenocortical cell nuclei PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0000646 enlarged adrenocortical cells PMID: 7628695 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0001753 hypersecretion of corticotropin-releasing hormone PMID: 10471508 
Nr3c1tm2Ljm|Tg(Camk2a-cre)T50Stl Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Camk2a-cre)T50Stl/?
involves: 129 * BALB/c * C57BL/6 * CBA
MGI:3531298  MGI:95824  MP:0001402 hypoactivity PMID: 15623560 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0006027 impaired respiratory alveologenesis PMID: 7628695 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0005129 increased adrenocorticotropin level PMID: 10471508 
Nr3c1tm2Gsc|Tg(Runx2-icre)1Jtuc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Runx2-icre)1Jtuc/0
involves: 129P2/OlaHsd * FVB/N
MGI:4455014  MGI:95824  MP:0001257 increased body length PMID: 20519123 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001748 increased circulating adrenocorticotropin level PMID: 7628695 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0002666 increased circulating aldosterone level PMID: 18697839 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0006375 increased circulating angiotensinogen level PMID: 18697839 
Nr3c1tm3Gsc Nr3c1tm3Gsc/Nr3c1tm3Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001745 increased circulating corticosterone level PMID: 9604929 
Nr3c1tm2Ljm|Tg(Camk2a-cre)T50Stl Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Camk2a-cre)T50Stl/?
involves: 129 * BALB/c * C57BL/6 * CBA
MGI:3531298  MGI:95824  MP:0001745 increased circulating corticosterone level PMID: 15623560 
Nr3c1tm2Gsc|Tg(Camk2a-cre/ERT2)2Gsc Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Camk2a-cre/ERT2)2Gsc/0
involves: 129P2/OlaHsd * FVB/N
MGI:3759303  MGI:95824  MP:0001745 increased circulating corticosterone level PMID: 17683525 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001745 increased circulating corticosterone level PMID: 7628695 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0001745 increased circulating corticosterone level PMID: 18697839 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0003367 increased circulating glucocorticoid level PMID: 10471508 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0009355 increased liver triglyceride level PMID: 18697839 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0004875 increased mean systemic arterial blood pressure PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0004875 increased mean systemic arterial blood pressure PMID: 19017639 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0005582 increased renin activity PMID: 18697839 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0009763 increased sensitivity to induced morbidity/mortality PMID: 12949501 
Nr3c1tm2Ljm|Tg(Lck-cre)548Jxm Nr3c1tm2Ljm/Nr3c1tm2Ljm,Tg(Lck-cre)548Jxm/?
involves: 129S6/SvEvTac * C57BL/6 * CBA
MGI:2176198  MGI:95824  MP:0008735 increased susceptibility to endotoxin shock PMID: 12949501 
Nr3c1+|Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1+
B6.129P2-Nr3c1
MGI:95824  MP:0004799 increased susceptibility to experimental autoimmune encephalomyelitis PMID: 18523311 
Nr3c1tm2Gsc|Tg(Lck-cre)I57Jxm Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Lck-cre)I57Jxm/0
B6.Cg-Nr3c1 Tg(Lck-cre)I57Jxm
MGI:2177579  MGI:95824  MP:0004799 increased susceptibility to experimental autoimmune encephalomyelitis PMID: 18523311 
Nr3c1+|Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1+
B6.Cg-Nr3c1
MGI:95824  MP:0006144 increased systemic arterial systolic blood pressure PMID: 18697839 
Nr3c1tm1Ljm Nr3c1tm1Ljm/Nr3c1tm1Ljm
involves: 129S6/SvEvTac * C57BL/6
MGI:95824  MP:0002058 neonatal lethality PMID: 12165507  12495930 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0002058 neonatal lethality PMID: 7628695 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0002058 neonatal lethality PMID: 12495930 
Nr3c1tm2.1Gsc Nr3c1tm2.1Gsc/Nr3c1tm2.1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0002058 neonatal lethality PMID: 10357937 
Nr3c1tm3Ljm Nr3c1tm3Ljm/Nr3c1tm3Ljm
involves: 129S6/SvEvTac * FVB/N
MGI:95824  MP:0002169 no abnormal phenotype detected PMID: 12133953 
Nr3c1tm2Gsc|Tg(Nes-cre)1Kln Nr3c1tm2Gsc/Nr3c1tm2Gsc,Tg(Nes-cre)1Kln/0
involves: 129P2/OlaHsd * C57BL/6J * SJL
MGI:2176172  MGI:95824  MP:0000066 osteoporosis PMID: 10471508 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0002081 perinatal lethality PMID: 10357937 
Nr3c1Gt(ESKN92)Hgs Nr3c1Gt(ESKN92)Hgs/Nr3c1Gt(ESKN92)Hgs
B6.Cg-Nr3c1
MGI:95824  MP:0002082 postnatal lethality PMID: 18697839 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd * C57BL/6
MGI:95824  MP:0001954 respiratory distress PMID: 7628695 
Nr3c1tm1Ljm Nr3c1tm1Ljm/Nr3c1tm1Ljm
involves: 129S6/SvEvTac * C57BL/6
MGI:95824  MP:0001953 respiratory failure PMID: 12495930 
Nr3c1tm1Gsc Nr3c1tm1Gsc/Nr3c1tm1Gsc
involves: 129P2/OlaHsd
MGI:95824  MP:0001953 respiratory failure PMID: 12495930 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002768 small adrenal glands PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0002768 small adrenal glands PMID: 19017639 
Nr3c1tm1Ljm Nr3c1tm1Ljm/Nr3c1tm1Ljm
involves: 129S6/SvEvTac * C57BL/6
MGI:95824  MP:0001179 thick alveolar septum PMID: 12165507 
Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1tm1Dage
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008302 thin adrenal cortex PMID: 19017639 
Nr3c1+|Nr3c1tm1Dage Nr3c1tm1Dage/Nr3c1+
involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL
MGI:95824  MP:0008302 thin adrenal cortex PMID: 19017639 
Clinically-Relevant Mutations and Pathophysiology
Disease:  Glucocorticoid hypersensitivity
Role: 
References:  23
Click column headers to sort
Type Species Molecular location Description Reference
polymorphism Human N363S 23
Disease:  Glucocorticoid resistance
OMIM:  138040
Orphanet:  786
Role: 
References:  6-7
Click column headers to sort
Type Species Molecular location Description Reference
nonsynonymous point mutation Human C421Y, R477H, I559N, D641V, G679S, V729I, I747M, L753F 6-7
Disease:  Acute childhood lymphoblastic leukemia
Role: 
References:  18
Mutations not determined
Disease:  Asthma
Role: 
References:  2,14
Mutations not determined
Clinically-Relevant Mutations and Pathophysiology Comments
In general glucocorticoid receptor (GR) polymorphisms have been associated with high blood pressure, insulin sensitivity, body mass index, increased visceral fat, and variations in tissue-specific steroid sensitivity. The N363S polymorphism of the GR results in an asparagine to serine amino acid substitution in a modulatory region of the receptor and phosphorylation of serine residues affects activation of GR target genes [16]. Many other diseases have been associated to certain GR polymorphisms, see GR SNPs.

REFERENCES

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3C. 3-Ketosteroid receptors: Glucocorticoid receptor. Last modified on 28/05/2014. Accessed on 20/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=625.

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