Gene Report

Basic Information

Approved Symbol	NR3C1
Approved Name	nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)
Previous Symbol	GRL
Previous Name	nuclear receptor subfamily 3, group C, member 1
Symbol Alias	GR
Location	5q31-q32
Position	chr5:142657496-142815077 (-)
External Links	Entrez Gene: 2908 Ensembl: ENSG00000113580 UCSC: uc003lnb.3 HGNC ID: 7978
No. of Studies (Positive/Negative)	7(7/0)
Type	Literature-origin; SNP mapped; Protein mapped

Positive relationships between NR3C1 and MDD (count: 7)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
glucocorticoid receptor (GR)	Klok, 2010	patients and normal controls	P-value<0.05	Significantly lower expression levels (30-50%) were detected...... Significantly lower expression levels (30-50%) were detected for MR or GR in hippocampal, inferior frontal gyrus and cingulate gyrus tissue from MDD patients (p < .05) More...
NR3C1	van West, 2006	patients and normal controls	P-value=0.02	In the Belgian sample, we observed significant allele (p=0.0...... In the Belgian sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with an SNP in the promoter region (NR3C1-1); in the Swedish sample, we observed significant allele (p=0.02) and genotype (p=0.02) association with the R23K SNP. More...
Gralpha	Matsubara, 2006	patients and normal controls		Reduced expression of GRalpha mRNA was shown in both bipolar...... Reduced expression of GRalpha mRNA was shown in both bipolar and major depressive disorder patients in a current depressive state as well as in remission. More...
GR	van Rossum EF, 2006	Patients and nomal controls		Homozygous carriers of the BclI polymorphism and ER22/23EK-c...... Homozygous carriers of the BclI polymorphism and ER22/23EK-carriers had an increased risk of developing a major depressive episode. More...
NR3C1	Zobel, 2008	patients and normal controls		We found association between the diagnosis of depression and...... We found association between the diagnosis of depression and DNA sequence variants in intron 2 as well as in the 5' region of the NR3C1 gene More...
glucocorticoid receptor	Alt, 2010	patients and normal controls	P-value<0.05	In MDD, total GR levels were unaltered, although GRalpha was...... In MDD, total GR levels were unaltered, although GRalpha was decreased in the amygdala and cingulate gyrus (p<0.05); transcripts containing exons 1B, 1C and 1F were lower, and 1D and1J were increased in some regions More...
NR3C1	Szczepankiewicz, 2011	patients and normal controls		We have found three polymorphisms (rs6198, rs6191 and rs3338...... We have found three polymorphisms (rs6198, rs6191 and rs33388) to be associated with major depressive disorder (MDD) More...

Positive relationships between NR3C1 and other components at different levels (count: 2)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Relation Description
Name in Literature	Related Components
glucocorticoid receptor		EGR1(NGFI-A)	gene	Alt, 2010	patients and normal controls	NGFI-A, a transcription factor of exon 1F of GR NGFI-A, a transcription factor of exon 1F of GR
NR3C1		Hippocampus(hippocampus)	brain morphology and function	Zobel, 2008	patients and normal controls	In patients, diagnosis-related alleles were also associated ...... In patients, diagnosis-related alleles were also associated to hippocampal volume reduction and amygdala volume variation. More...

Positive relationship network of NR3C1 in MK4MDD

Network loading ...

Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between NR3C1 and MDD (count: 0)

Negative relationships between NR3C1 and other components at different levels (count: 0)

NR3C1 related SNPs in MK4MDD (count: 3)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs33388	chr5:142697295(Forward)	intron_variant; nc_transcript_variant	1(1/0)
rs6191	chr5:142658156(Forward)	3_prime_UTR_variant; downstream_gene_variant	1(1/0)
rs6198	chr5:142657621(Forward)	3_prime_UTR_variant; downstream_gene_variant	1(1/0)

NR3C1 related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Glucocorticoid receptor	P04150	1(1/0)	Literature-origin

NR3C1 related GO terms (count: 26)

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005634	nucleus	cellular component	IDA
GO:0007165	signal transduction	biological process	TAS[7769088]
GO:0043565	sequence-specific DNA binding	molecular function	IEA
GO:0005759	mitochondrial matrix	cellular component	TAS[10887960]
GO:0043525	positive regulation of neuron apoptotic process	biological process	IEA
GO:0030325	adrenal gland development	biological process	IEA
GO:0008211	glucocorticoid metabolic process	biological process	IEA
GO:0004883	glucocorticoid receptor activity	molecular function	IEA
GO:0060603	mammary gland duct morphogenesis	biological process	IEA
GO:0006367	transcription initiation from RNA polymerase II promoter	biological process	TAS
GO:0005737	cytoplasm	cellular component	IDA
GO:0005654	nucleoplasm	cellular component	TAS
GO:0046983	protein dimerization activity	molecular function	IEA
GO:0005496	steroid binding	molecular function	IEA
GO:0006366	transcription from RNA polymerase II promoter	biological process	TAS[8621628]
GO:0008270	zinc ion binding	molecular function	IEA
GO:0010467	gene expression	biological process	TAS
GO:0005730	nucleolus	cellular component	IDA
GO:0006351	transcription, DNA-dependent	biological process	TAS[10887960]
GO:0005829	cytosol	cellular component	IEA
GO:0005515	protein binding	molecular function	IPI[12552091]
GO:0031946	regulation of glucocorticoid biosynthetic process	biological process	IEA
GO:0016020	membrane	cellular component	IEA
GO:0016568	chromatin modification	biological process	IEA
GO:0006111	regulation of gluconeogenesis	biological process	IEA
GO:0003700	sequence-specific DNA binding transcription factor activity	molecular function	IEA

NR3C1 related KEGG pathways (count: 1)

Gene mapped KEGG pathways
ID	Name	Brief Description	Full Description
hsa04080	neuroactive ligand_receptor_interaction	Neuroactive ligand-receptor interaction

NR3C1 related BioCarta pathways (count: 2)

ID	Name	Brief Description	Full Description
Literature-origin BioCarta pathway
NTHI_PATHWAY	nthi pathway	NFkB activation by Nontypeable Hemophilus influenzae	The role of Hemophilus influenzae in ear infections and chro...... The role of Hemophilus influenzae in ear infections and chronic obstructive pulmonary disease includes the induction of an inflammatory response through activation of the transcription factor NF-kB. In addition to activation of inflammatory cytokine genes like IL-1 and TNF, H. influenzae activates TLR2 expression and genes involved in mucus production. Hemophilus influenzae activates NF-kB by multiple mechanisms, starting with activation of the Toll-like receptor 2 (TLR2) by the p16 protein in the H. influenzae outer membrane. TLR2 plays a key role in innate immune responses and is expressed in high levels in lymphoid cells as well as low levels in epithelial cells. The role of TLR2 was supported by blocking NF-kB activation with a dominant negative TLR2 and increasing it with transfection of a normal TLR2 gene. TLR2 in turn activates TAK1, which activates two divergent signaling pathways. One of these pathways leads to IkB kinase activation, IkB phosphorylation and degradation, releasing the NF-kB heterodimer to translocate into the nucleus and activate transcription of target genes. In the alternate pathway, TAK1 also activates NF-kB through a Map kinase pathway, activating p38 and NF-kB in a nuclear translocation independent manner. Investigation of the mechanisms of H. influenzae signaling involved in NF-kB activation may provide the information needed to develop better treatments for inflammatory conditions caused by this pathogen. Other pathways modulate the role of NF-kB in H. influenzae pathogenesis. Glucocorticoids widely used as anti-inflammatory drugs increase TLR2 activation by H. influenzae through the NIK/I-kB kinase pathway, while they repress the p38 dependent activation of NF-kB. The repression of the p38 pathway by glucocorticoids occurs through activation of the MAP kinase phosphatase-1 (MKP-1) which dephosphorylates and deactivates p38. Another aspect of the inflammatory response to H. influenzae infection is the production of excessive mucus, contributing to the overall symptoms of infection. NF-kB activation of the Muc2 gene contributes to mucus overproduction, in addition to H. influenzae activation of the TGF-beta receptor, activating SMAD transcription factors SMAD3 and SMAD4. Understanding mechanisms that modify H. influenzae signaling will contribute to further understanding the pathogenesis and treatment of ear infections and chronic obstructive pulmonary disease. More...

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
GCR_PATHWAY	gcr pathway	Corticosteroids and cardioprotection	Myocardial infarction damages heart tissue both during the i...... Myocardial infarction damages heart tissue both during the initial ischemia and the subsequent reperfusion of tissues with oxygen. Corticosteroids can protect cardiac tissue from damage following a heart attack, but the mechanisms by which corticosteroids are cardioprotective have not been clear and negative side effects such as reduced wound healing may result from their use. Corticosteroids exert a variety of actions through binding to the glucocorticoid receptor (GR), a member of the steroid hormone receptor gene family. GR acts as a ligand-dependent transcription factor, but some of the cardioprotective effects mediated by GR-bound corticosteroids are non-transcriptional in nature. Glucocorticoids are commonly used as anti-inflammatory drugs in a variety of conditions, and some of their effects in the heart result from inhibition of the inflammatory response of heart tissue to ischemia and reperfusion. NF-kB is a transcription factor involved in signaling by inflammatory factors such as TNF, and is repressed by glucocorticoids. Annexin-1 is a calcium-dependent phospholipid binding protein whose expression is induced by corticosteroids and inhibits the infiltration of neutrophils into tissue, blocking reperfusion-induced inflammatory heart damage. A non-transcriptional cardioprotective effect of glucocorticoids is activation of NO production by endothelial nitric oxide synthase (eNOS). Glucocorticoids activate eNOS through activation of PI3 kinase and AKT and increased NO produced by eNOS can diffuse into surrounding tissues to prevent clotting and cause vasodilation. The beta-2 adrenergic receptor can also activate PI3 kinase and may synergize with glucocorticoids in this pathway. The atrial natriuretic factor (ANF) is a peptide secreted by the atrial wall in response to increased atrial pressure such as occurs during cardiac failure and to be decreased by myocardial infarction. Glucocorticoids increase the secretion of ANF by acting at the transcriptional level to increase expression of the pro-ANF peptide, perhaps inducing increased water excretion in the kidneys to reduce blood volume and reduce atrial pressure. The exploration of glucorticoid responses may allow the identification of compounds that retain the cardioprotective activities but do not inhibit wound healing. Alternative mechanisms of eNOS activation may also provide a route to identify cardioprotective drugs. More...

NR3C1 related Reactome pathways (count: 2)

ID	Name	Description
Gene mapped Reactome pathways
REACT_71	gene expression	Gene Expression covers the process of transcription of mRNA ...... Gene Expression covers the process of transcription of mRNA genes, the processing of pre-mRNA, and its subsequent translation to result in a protein. The expression of non-protein-coding genes is not included in this section yet. However, the transcription of RNAs other than mRNA is described in the section on transcription; in the sections 'RNA Polymerase I Transcription', and 'RNA Polymerase III Transcription'. More...
REACT_15525	nuclear receptor_transcription_pathway	A classic example of bifunctional transcription factors is t...... A classic example of bifunctional transcription factors is the family of Nuclear Receptor ). For example, binding of thyroid hormone (TH) to the human TH Receptor (THRA or THRB) was found to result in the recruitment of a specific complex of Thyroid Receptor Associated Proteins - the TRAP coactivator complex - of which the TRAP220 subunit was later identified to be the Mediator 1 (MED1) homologue. Similarly, binding of Vitamin D to the human Vitamin D3 Receptor was found to result in the recruitment of a specific complex of D Receptor Interacting Proteins - the DRIP coactivator complex, of which the DRIP205 subunit was later identified to be human MED1. More...

NR3C1 related interactors from protein-protein interaction data in HPRD (count: 90)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
NR3C1	DDX54	No	in vitro	12466272
NR3C1	CALR	No	in vivo	8107808 , 9089287
NR3C1	PSMC3IP	No	in vitro;in vivo;yeast 2-hybrid	11739747
NR3C1	MDM2	No	in vivo	11562347
NR3C1	ZBTB16	Yes	in vitro	14521715
NR3C1	ETS1	No	in vitro	11279115
NR3C1	NR2F6	No	in vitro	10713182
NR3C1	HSPA1A	No	in vivo	12093808
NR3C1	RAF1	No	in vivo	11005817
NR3C1	PRKDC	No	in vitro	9038175
NR3C1	GRIP1	No	in vitro	16362036
NR3C1	UBE2I	No	in vitro;yeast 2-hybrid	11812797
NR3C1	FYN	No	in vivo	16888650
NR3C1	CEBPA	No	in vitro;in vivo	11818365
NR3C1	RELA	No	in vitro;in vivo	10995388 , 7659084 , 8290595
NR3C1	SMAD3	No	in vitro;in vivo	12902338 , 10518526
NR3C1	COPS6	No	in vitro	12237292
NR3C1	ONECUT1	No	in vitro	10430878
NR3C1	SMARCE1	No	in vitro;in vivo	12917342
NR3C1	NCOR2	No	in vitro	12011091
NR3C1	BAG1	No	in vitro;in vivo	9603979 , 11101523 , 10477749
NR3C1	CHD9	No	in vitro;in vivo	16523501
NR3C1	CREB1	Yes	in vitro	7621901 , 8449898
NR3C1	SUMO4	No	in vivo	16236267
NR3C1	STAT5A	No	in vitro;in vivo	9528750
NR3C1	TBP	No	in vivo	9649342
NR3C1	IDE	No	in vivo	8051160
NR3C1	TXN	No	in vitro	9915858
NR3C1	HNRNPU	No	in vivo	9353307
NR3C1	ADA	No	in vitro	9154805
NR3C1	SUMO1	No	in vivo	12193561 , 12144530
NR3C1	IFNGR2	No	in vitro	8349631
NR3C1	TSG101	No	yeast 2-hybrid	10508170
NR3C1	KDM5A	No	in vitro	11358960
NR3C1	NFKB1	No	in vitro	7823959 , 8290595
NR3C1	DCAF6	No	in vitro;in vivo	15784617
NR3C1	PTMS	No	in vitro	10601862
NR3C1	MAPK15	No	yeast 2-hybrid	16624805
NR3C1	MAPK8	Yes	in vitro;in vivo	12351702 , 9199329
NR3C1	POU2F1	No	in vitro;in vivo	10490647 , 10480874 , 9584182 , 14522952 , 11096094
NR3C1	UBB	No	in vivo	11146632
NR3C1	NCOR1	No	in vitro;in vivo	12011091
NR3C1	NFKB2	No	in vitro;in vivo	7823959
NR3C1	JUN	Yes	in vitro;in vivo	8733011 , 7823959
NR3C1	NRIP1	No	in vitro;in vivo	12773562 , 10364267
NR3C1	NCOA2	No	in vitro	12151000
NR3C1	ECD	No	yeast 2-hybrid	9928932
NR3C1	TRIM24	No	in vivo	9115274
NR3C1	CREBBP	Yes	in vitro	9649342
NR3C1	PRPF6	No	in vivo	12039962
NR3C1	NR3C2	Yes	in vitro;in vivo	11154266
NR3C1	PPARGC1A	No	in vitro	10713165
NR3C1	SMARCA2	No	in vivo	8223438
NR3C1	SYT1	No	in vivo;yeast 2-hybrid	16143103
NR3C1	SMARCA4	No	in vitro	9590696
NR3C1	HSP90AA1	No	in vitro	8898375 , 9334248 , 8645634 , 10066374 , 8621522
NR3C1	PBX1	No	in vivo	12487626
NR3C1	NR2F2	No	in vitro;in vivo;yeast 2-hybrid	14739255
NR3C1	KPNA2	No	in vivo	12933681
NR3C1	TP53	No	in vitro;in vivo	11080152
NR3C1	TGFB1I1	No	yeast 2-hybrid	10848625
NR3C1	SFN	No	yeast 2-hybrid	12730237
NR3C1	PELP1	No	in vitro	12415108
NR3C1	NCOA1	No	in vitro;yeast 2-hybrid	12917342 , 12118039 , 12569182
NR3C1	NCL	No	in vitro;in vivo	11162542 , 8530516
NR3C1	FKBP4	Yes	in vitro	8341706
NR3C1	SLC25A4	No	in vivo	12039962
NR3C1	CALM1	No	in vitro;in vivo	7887964
NR3C1	MAPK1	Yes	in vitro;in vivo	12351702 , 9199329
NR3C1	NCOA6	No	yeast 2-hybrid	10866662
NR3C1	TRIM28	No	in vitro;in vivo	9742105
NR3C1	STAT3	No	in vivo	14522952 , 9388192
NR3C1	NR3C1	Yes	in vitro;yeast 2-hybrid	12773573 , 9482670 , 10364267
NR3C1	ETS2	No	in vitro;in vivo	11279115
NR3C1	PTGES3	No	in vivo	10691735
NR3C1	YWHAH	No	in vitro;yeast 2-hybrid	9079630 , 12730237 , 11266503
NR3C1	POU1F1	No	in vitro	9426156
NR3C1	RNF14	No	in vitro;in vivo	10085091
NR3C1	RARA	No	yeast 2-hybrid	17641689
NR3C1	DAP3	Yes	in vitro;in vivo;yeast 2-hybrid	12099703 , 10903152
NR3C1	STAT5B	No	in vitro;in vivo	11158330 , 8878484 , 9528750
NR3C1	SMARCD1	No	in vitro;in vivo	12917342
NR3C1	MED14	No	in vitro;yeast 2-hybrid	10508170
NR3C1	SMARCC1	No	in vitro	9590696
NR3C1	CEBPB	No	in vitro;in vivo	9817600
NR3C1	SMARCB1	No	in vitro;in vivo	10688647
NR3C1	PRKACA	No	in vitro;in vivo	11027313
NR3C1	LCK	No	in vivo	16888650
NR3C1	POU2F2	No	in vitro	10490647 , 10480874 , 9584182
NR3C1	AR	Yes	in vitro;yeast 2-hybrid	9162033

Gene Report

Gene mapped GO terms

Gene mapped KEGG pathways

Literature-origin BioCarta pathway

Gene mapped BioCarta pathways

Gene mapped Reactome pathways