
Gene Report
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 |
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... |
Genetic/epigenetic locus | Protein and other molecule | Cell and molecular pathway | Neural system | Cognition and behavior | Symptoms and signs | Environment | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
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. 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

#rs | Location | Annotation | No. of Studies (Positive/Negative) | |
---|---|---|---|---|
rs6198 | chr5:142657621(Forward) | 3_prime_UTR_variant; downstream_gene_variant | 1(1/0) | |
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) |
Approved Name | UniportKB | No. of Studies (Positive/Negative) | Source | |
---|---|---|---|---|
Glucocorticoid receptor | P04150 | 1(1/0) | Literature-origin |
Gene mapped GO terms | ||||
ID | Name | Type | Evidence | |
---|---|---|---|---|
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 |
Gene mapped KEGG pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
hsa04080 | neuroactive ligand_receptor_interaction | Neuroactive ligand-receptor interaction |
Literature-origin BioCarta pathway | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
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... |
Gene mapped BioCarta pathways | ||||
ID | Name | Brief Description | Full Description | |
---|---|---|---|---|
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... |
Gene mapped Reactome pathways | |||
ID | Name | Description | |
---|---|---|---|
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... | |
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... |

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