IUPHAR DATABASE | 3C. 3-Ketosteroid receptors

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Glucocorticoid receptor

Systematic Nomenclature: NR3C1

Family: 3C. 3-Ketosteroid receptors

Contents:

Gene and Protein Information

Previous and Unofficial Names

Database Links

Selected 3D Structures

Physiological Consequences of Altering Gene Expression

Phenotypes, Alleles and Disease Models

Clinically-Relevant Mutations and Pathophysiology

References

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)	18
Mouse	792	18 20.0 cM	Nr3c1	nuclear receptor subfamily 3, group C, member 1	12
Rat	794	18p12	Nr3c1	nuclear receptor subfamily 3, group C, member 1	31

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

Previous and Unofficial Names

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	25 (Hs), 12104 (Rn)
DrugBank Target	871 (Hs)
Ensembl	ENSG00000113580 (Hs), ENSMUSG00000024431 (Mm), ENSRNOG00000014096 (Rn)
Entrez Gene	2908 (Hs), 14815 (Mm), 24413 (Rn)
GeneCards	NR3C1 (Hs)
GenitoUrinary Development Molecular Anatomy Project	Nr3c1 (Mm)
HomoloGene	30960 (Hs)
Human Protein Reference Database	00679 (Hs)
InterPro	P04150 (Hs), P06537 (Mm), P06536 (Rn)
KEGG Gene	hsa:2908 (Hs), mmu:14815 (Mm), rno:24413 (Rn)
NURSA Receptor	3C1
OMIM	138040 (Hs)
Orphanet Gene	ORPHA123916 (Hs)
PharmGKB Gene	PA181 (Hs)
PhosphoSitePlus	P04150 (Hs), P06537 (Mm), P06536 (Rn)
RefSeq Nucleotide	NM_000176 (Hs), NM_008173 (Mm), NM_012576 (Rn)
RefSeq Protein	NP_001019265 (Hs), NP_032199 (Mm), NP_036708 (Rn)
TreeFam	ENSG00000113580 (Hs), ENSMUSG00000024431 (Mm), ENSRNOG00000014096 (Rn)
UniProt	P04150 (Hs), P06537 (Mm), P06536 (Rn)
	Steroid hormone

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:	25

Search for other structures on the PDB

Search by keyword: Glucocorticoid receptor

Search by accession number: P04150, P06536, P06537

Natural/Endogenous Ligand(s)
aldosterone
corticosterone
cortisol
deoxycortisone
Comments: cortisol and corticosterone are the principal endogenous agonists

Rank order of potency (Human)
cortisol,corticosterone>>aldosterone,deoxycortisone [42]

Rank order of potency (Human)

cortisol,corticosterone>>aldosterone,deoxycortisone [42]

Agonists

Key to terms and symbols

View all chemical structures

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Ligand	Sp.	Action	Affinity	Units	Reference
dexamethasone	Hs	Agonist	8.1 – 9.0	pIC₅₀	17,29,42
triamcinolone acetonide	Hs	Agonist	8.2	pIC₅₀	14,53
prednisolone	Hs	Agonist	7.8	pIC₅₀	29
triamcinolone	Hs	Agonist	7.7	pIC₅₀	29
cortisol	Hs	Agonist	7.3 – 8.0	pIC₅₀	17,29,42
corticosterone	Mm	Agonist	7.2	pIC₅₀	17,29,42
deoxycorticosterone	Hs	Agonist	7.2	pIC₅₀	29,42

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.

Antagonists

Key to terms and symbols

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Ligand					Sp.	Action	Affinity	Units	Reference
mifepristone					Hs	Antagonist	9.4	pK_d	16,42

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	2,48
AP1	Physical, Functional	transactivation	22,44,52
NF-κB	Physical, Functional	transactivation	5,43
14-3-3ρ	Physical, Functional	cellular localization, transactivation	26
HSP90	Physical, Functional	Cellular localization	37-39

Main Co-regulators
Name	Activity	Specific	Ligand dependent	AF-2 dependent	Comments	References
CREBBP	Co-activator	No	Yes	Yes	Histone acetyltransferase, a transcriptional cointegrator	23
NCOA2	Co-activator	No	Yes	Yes		19,47,49
PTMS	Co-activator	Yes	Yes	No	Has little effect on ER-mediated transactivation.	36
NCOA6	Co-activator	No	Yes	Yes	Likely a member of multimeric complex including NIF-1.	28
MED1	Co-activator	No	Yes	Yes		40
BAG1	Co-repressor	No	No	Yes	A regulator of HSP70 and a co-repressor.	27

Main Target Genes
Name	Species	Effect	Technique	Comments	References
PCK1	Human	Both	ChIP, Transient transfection		6
Dusp1	Mouse	Activated	Transient transfection	Dusp1 is also known as MAP kinase phosphatase-1 (MKP-1)	24
annexin A1	Human	Activated	Transient transfection, other	Also known as Lipocrotin-1	32,41
Interleukin 8	Human	Repressed			46
TNF	Human	Repressed			50

Tissue Distribution

ubiquitous

Species:	Human
Technique:	Northern, Q-PCR, In situ, Western, Immunohistology, Other
References:	7,18,30,34-35

Tissue Distribution Comments

GR is expressed ubiquitously in mammals

Functional Assays

Thymocyte-killing effects.

Species:	Rat
Tissue:	thymus
Response measured:	thymus weight. Thymocytes undergo apoptosis in a GR-dependent manner.
References:	8

Hyperglycemic effect

Species:	Human
Tissue:	serum
Response measured:	Blood glucose level is elevated by intravenous injection of glucocorticoids.
References:	45,51

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:	21

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:	9-10

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:	33

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
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0000013	abnormal adipose tissue distribution	PMID: 10471508
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0008504	abnormal adrenal chromaffin cell morphology	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0008504	abnormal adrenal chromaffin cell morphology	PMID: 10357937
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0008504	abnormal adrenal chromaffin cell morphology	PMID: 10357937
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0008288	abnormal adrenal cortex morphology	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0000639	abnormal adrenal gland morphology	PMID: 7628695
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0000639	abnormal adrenal gland morphology	PMID: 18697839
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0003962	abnormal adrenaline level	PMID: 7628695
Nr3c1^tm2Gsc\|Tg(Drd1a-cre)AGsc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,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⁺\|Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1⁺ B6.129P2-Nr3c1	MGI:95824	MP:0005167	abnormal blood-brain barrier function	PMID: 18523311
Nr3c1^tm2Gsc\|Tg(Runx2-icre)1Jtuc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Runx2-icre)1Jtuc/0 involves: 129P2/OlaHsd * FVB/N	MGI:4455014 MGI:95824	MP:0010119	abnormal bone mineral density	PMID: 20519123
Nr3c1^tm2Gsc\|Tg(Runx2-icre)1Jtuc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Runx2-icre)1Jtuc/0 involves: 129P2/OlaHsd * FVB/N	MGI:4455014 MGI:95824	MP:0008271	abnormal bone ossification	PMID: 20519123
Nr3c1^tm2Gsc\|Tg(Runx2-icre)1Jtuc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Runx2-icre)1Jtuc/0 involves: 129P2/OlaHsd * FVB/N	MGI:4455014 MGI:95824	MP:0000130	abnormal cancellous bone morphology	PMID: 20519123
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0000494	abnormal cecum morphology	PMID: 12949501
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0005345	abnormal circulating corticosterone level	PMID: 18697839
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0002065	abnormal fear/anxiety-related behavior	PMID: 10471508
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0008750	abnormal interferon level	PMID: 12949501
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0008751	abnormal interleukin level	PMID: 12949501
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0000609	abnormal liver physiology	PMID: 7628695
Nr3c1^tm1Ljm	Nr3c1^tm1Ljm/Nr3c1^tm1Ljm involves: 129S6/SvEvTac * C57BL/6	MGI:95824	MP:0001176	abnormal lung development	PMID: 12165507
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001176	abnormal lung development	PMID: 7628695
Nr3c1^tm1Ljm	Nr3c1^tm1Ljm/Nr3c1^tm1Ljm involves: 129S6/SvEvTac * C57BL/6	MGI:95824	MP:0001175	abnormal lung morphology	PMID: 12165507
Nr3c1^tm2Gsc\|Tg(Wap-cre)1Gsc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Wap-cre)1Gsc/0 involves: 129P2/OlaHsd * FVB/N	MGI:3527253 MGI:95824	MP:0009506	abnormal mammary gland alveolus morphology	PMID: 15471946
Nr3c1^tm2Gsc\|Tg(Wap-cre)1Gsc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Wap-cre)1Gsc/0 involves: 129P2/OlaHsd * FVB/N	MGI:3527253 MGI:95824	MP:0006269	abnormal mammary gland growth during pregnancy	PMID: 15471946
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6 * SJL	MGI:2176172 MGI:95824	MP:0002272	abnormal nervous system electrophysiology	PMID: 19234455
Nr3c1^tm2Gsc\|Tg(Drd1a-cre)AGsc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Drd1a-cre)AGsc/0 involves: 129P2/OlaHsd * C57BL/6 * FVB/N	MGI:3761815 MGI:95824	MP:0002272	abnormal nervous system electrophysiology	PMID: 19234455
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0003964	abnormal noradrenaline level	PMID: 7628695
Nr3c1^tm2Gsc\|Tg(Runx2-icre)1Jtuc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Runx2-icre)1Jtuc/0 involves: 129P2/OlaHsd * FVB/N	MGI:4455014 MGI:95824	MP:0008395	abnormal osteoblast differentiation	PMID: 20519123
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd * 129X1/SvJ	MGI:95824	MP:0008395	abnormal osteoblast differentiation	PMID: 20519123
Nr3c1^tm3Gsc	Nr3c1^tm3Gsc/Nr3c1^tm3Gsc involves: 129P2/OlaHsd * FVB/N	MGI:95824	MP:0005006	abnormal osteoblast physiology	PMID: 20519123
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd * 129X1/SvJ	MGI:95824	MP:0005006	abnormal osteoblast physiology	PMID: 20519123
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008872	abnormal physiological response to xenobiotic	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008872	abnormal physiological response to xenobiotic	PMID: 19017639
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0003115	abnormal respiratory system development	PMID: 7628695
Nr3c1^tm1Ljm	Nr3c1^tm1Ljm/Nr3c1^tm1Ljm involves: 129S6/SvEvTac * C57BL/6	MGI:95824	MP:0009258	abnormal thymocyte apoptosis	PMID: 12165507
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0003118	abnormal tracheal-bronchial branching morphogenesis	PMID: 7628695
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0008752	abnormal tumor necrosis factor level	PMID: 12949501
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0008294	abnormal zona fasciculata morphology	PMID: 7628695
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0008294	abnormal zona fasciculata morphology	PMID: 18697839
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008294	abnormal zona fasciculata morphology	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008294	abnormal zona fasciculata morphology	PMID: 19017639
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0008293	abnormal zona glomerulosa morphology	PMID: 18697839
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0008295	abnormal zona reticularis morphology	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0000643	absent adrenal medulla	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0000645	absent adrenergic chromaffin cells	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0001742	absent circulating adrenaline	PMID: 10357937
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0001742	absent circulating adrenaline	PMID: 10357937
Nr3c1^tm2Ljm\|Tg(Camk2a-cre)T50Stl	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Camk2a-cre)T50Stl/? involves: 129 * BALB/c * C57BL/6 * CBA	MGI:3531298 MGI:95824	MP:0001899	absent long term depression	PMID: 15623560
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001177	atelectasis	PMID: 7628695
Nr3c1^tm2Ljm\|Tg(Camk2a-cre)T50Stl	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Camk2a-cre)T50Stl/? involves: 129 * BALB/c * C57BL/6 * CBA	MGI:3531298 MGI:95824	MP:0002573	behavioral despair	PMID: 15623560
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0009481	cecum inflammation	PMID: 12949501
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001575	cyanosis	PMID: 7628695
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0001364	decreased anxiety-related response	PMID: 10471508
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0005017	decreased B cell number	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0005017	decreased B cell number	PMID: 19017639
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0001258	decreased body length	PMID: 10471508
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0001265	decreased body size	PMID: 10471508
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0001262	decreased body weight	PMID: 10471508
Nr3c1^tm2Gsc\|Tg(Runx2-icre)1Jtuc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Runx2-icre)1Jtuc/0 involves: 129P2/OlaHsd * FVB/N	MGI:4455014 MGI:95824	MP:0000063	decreased bone density	PMID: 20519123
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0010121	decreased bone mineral density	PMID: 10471508
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008075	decreased CD4-positive T cell number	PMID: 19017639
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008079	decreased CD8-positive T cell number	PMID: 19017639
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0002664	decreased circulating adrenocorticotropin level	PMID: 10471508
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002664	decreased circulating adrenocorticotropin level	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002664	decreased circulating adrenocorticotropin level	PMID: 19017639
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002665	decreased circulating corticosterone level	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002665	decreased circulating corticosterone level	PMID: 19017639
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0005664	decreased circulating noradrenaline level	PMID: 10357937
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0005664	decreased circulating noradrenaline level	PMID: 10357937
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002780	decreased circulating testosterone level	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002780	decreased circulating testosterone level	PMID: 19017639
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0008973	decreased erythroid progenitor cell number	PMID: 10580006
Nr3c1^tm3Gsc	Nr3c1^tm3Gsc/Nr3c1^tm3Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0008973	decreased erythroid progenitor cell number	PMID: 10580006
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0003884	decreased macrophage cell number	PMID: 19017639
Nr3c1^tm2Gsc\|Tg(Lck-cre)I57Jxm	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,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
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0008770	decreased survivor rate	PMID: 10357937 12495930
Nr3c1⁺\|Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1⁺ B6.129P2-Nr3c1	MGI:95824	MP:0006414	decreased T cell apoptosis	PMID: 16424199
Nr3c1^tm2Gsc\|Tg(Lck-cre)I57Jxm	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Lck-cre)I57Jxm/0 B6.Cg-Nr3c1 Tg(Lck-cre)I57Jxm	MGI:2177579 MGI:95824	MP:0006414	decreased T cell apoptosis	PMID: 18523311
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0000642	enlarged adrenal glands	PMID: 7628695
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0000642	enlarged adrenal glands	PMID: 18697839
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0008292	enlarged adrenocortical cell nuclei	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0000646	enlarged adrenocortical cells	PMID: 7628695
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0001753	hypersecretion of corticotropin-releasing hormone	PMID: 10471508
Nr3c1^tm2Ljm\|Tg(Camk2a-cre)T50Stl	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Camk2a-cre)T50Stl/? involves: 129 * BALB/c * C57BL/6 * CBA	MGI:3531298 MGI:95824	MP:0001402	hypoactivity	PMID: 15623560
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0006027	impaired respiratory alveologenesis	PMID: 7628695
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0005129	increased adrenocorticotropin level	PMID: 10471508
Nr3c1^tm2Gsc\|Tg(Runx2-icre)1Jtuc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Runx2-icre)1Jtuc/0 involves: 129P2/OlaHsd * FVB/N	MGI:4455014 MGI:95824	MP:0001257	increased body length	PMID: 20519123
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001748	increased circulating adrenocorticotropin level	PMID: 7628695
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0002666	increased circulating aldosterone level	PMID: 18697839
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0006375	increased circulating angiotensinogen level	PMID: 18697839
Nr3c1^tm3Gsc	Nr3c1^tm3Gsc/Nr3c1^tm3Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001745	increased circulating corticosterone level	PMID: 9604929
Nr3c1^tm2Ljm\|Tg(Camk2a-cre)T50Stl	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Camk2a-cre)T50Stl/? involves: 129 * BALB/c * C57BL/6 * CBA	MGI:3531298 MGI:95824	MP:0001745	increased circulating corticosterone level	PMID: 15623560
Nr3c1^tm2Gsc\|Tg(Camk2a-cre/ERT2)2Gsc	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Camk2a-cre/ERT2)2Gsc/0 involves: 129P2/OlaHsd * FVB/N	MGI:3759303 MGI:95824	MP:0001745	increased circulating corticosterone level	PMID: 17683525
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001745	increased circulating corticosterone level	PMID: 7628695
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0001745	increased circulating corticosterone level	PMID: 18697839
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0003367	increased circulating glucocorticoid level	PMID: 10471508
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0009355	increased liver triglyceride level	PMID: 18697839
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0004875	increased mean systemic arterial blood pressure	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0004875	increased mean systemic arterial blood pressure	PMID: 19017639
Nr3c1⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0005582	increased renin activity	PMID: 18697839
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0009763	increased sensitivity to induced morbidity/mortality	PMID: 12949501
Nr3c1^tm2Ljm\|Tg(Lck-cre)548Jxm	Nr3c1^tm2Ljm/Nr3c1^tm2Ljm,Tg(Lck-cre)548Jxm/? involves: 129S6/SvEvTac * C57BL/6 * CBA	MGI:2176198 MGI:95824	MP:0008735	increased susceptibility to endotoxin shock	PMID: 12949501
Nr3c1⁺\|Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1⁺ B6.129P2-Nr3c1	MGI:95824	MP:0004799	increased susceptibility to experimental autoimmune encephalomyelitis	PMID: 18523311
Nr3c1^tm2Gsc\|Tg(Lck-cre)I57Jxm	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,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⁺\|Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1⁺ B6.Cg-Nr3c1	MGI:95824	MP:0006144	increased systemic arterial systolic blood pressure	PMID: 18697839
Nr3c1^tm1Ljm	Nr3c1^tm1Ljm/Nr3c1^tm1Ljm involves: 129S6/SvEvTac * C57BL/6	MGI:95824	MP:0002058	neonatal lethality	PMID: 12165507 12495930
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0002058	neonatal lethality	PMID: 7628695
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0002058	neonatal lethality	PMID: 12495930
Nr3c1^tm2.1Gsc	Nr3c1^tm2.1Gsc/Nr3c1^tm2.1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0002058	neonatal lethality	PMID: 10357937
Nr3c1^tm3Ljm	Nr3c1^tm3Ljm/Nr3c1^tm3Ljm involves: 129S6/SvEvTac * FVB/N	MGI:95824	MP:0002169	no abnormal phenotype detected	PMID: 12133953
Nr3c1^tm2Gsc\|Tg(Nes-cre)1Kln	Nr3c1^tm2Gsc/Nr3c1^tm2Gsc,Tg(Nes-cre)1Kln/0 involves: 129P2/OlaHsd * C57BL/6J * SJL	MGI:2176172 MGI:95824	MP:0000066	osteoporosis	PMID: 10471508
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0002081	perinatal lethality	PMID: 10357937
Nr3c1^{Gt(ESKN92)Hgs}	Nr3c1^{Gt(ESKN92)Hgs}/Nr3c1^{Gt(ESKN92)Hgs} B6.Cg-Nr3c1	MGI:95824	MP:0002082	postnatal lethality	PMID: 18697839
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd * C57BL/6	MGI:95824	MP:0001954	respiratory distress	PMID: 7628695
Nr3c1^tm1Ljm	Nr3c1^tm1Ljm/Nr3c1^tm1Ljm involves: 129S6/SvEvTac * C57BL/6	MGI:95824	MP:0001953	respiratory failure	PMID: 12495930
Nr3c1^tm1Gsc	Nr3c1^tm1Gsc/Nr3c1^tm1Gsc involves: 129P2/OlaHsd	MGI:95824	MP:0001953	respiratory failure	PMID: 12495930
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002768	small adrenal glands	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1⁺ involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0002768	small adrenal glands	PMID: 19017639
Nr3c1^tm1Ljm	Nr3c1^tm1Ljm/Nr3c1^tm1Ljm involves: 129S6/SvEvTac * C57BL/6	MGI:95824	MP:0001179	thick alveolar septum	PMID: 12165507
Nr3c1^tm1Dage	Nr3c1^tm1Dage/Nr3c1^tm1Dage involves: 129P1/ReJ * C57BL/6 * C57BL/6J * SJL	MGI:95824	MP:0008302	thin adrenal cortex	PMID: 19017639
Nr3c1⁺\|Nr3c1^tm1Dage	Nr3c1^tm1Dage/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:	N363S polymorphism
References:	20

Click column headers to sort

Type	Species	Molecular location	Description	Reference
polymorphism	Human	N363S		20

Disease:	Asthma
Role:	mutations in the GR gene
References:	1,11

Mutations not determined

Disease:	Acute childhood lymphoblastic leukemia
Role:	mutations in the GR gene
References:	15

Mutations not determined

Disease:	Glucocorticoid resistance
OMIM:	138040
Orphanet:	786
Role:	point mutations in the GR gene
References:	3-4

Click column headers to sort

Type	Species	Molecular location	Description	Reference
nonsynonymous point mutation	Human	C421Y, R477H, I559N, D641V, G679S, V729I, I747M, L753F		3-4

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. [13]. 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 01/04/2013. Accessed on 20/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=625.

3C. 3-Ketosteroid receptors
	Introduction
	Contributors
	References
	Androgen receptor
	Glucocorticoid receptor
	Mineralocorticoid receptor
	Progesterone receptor