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Gene Report
| Basic information | Related studies | Functional annotation | Related other genetic factors | Overlap with SZ and MDD | ADD to My Gene Set | Comment on Gene | View All Comments on Gene |
| Approved Symbol | NR3C1 |
|---|---|
| Previous Symbol | GRL |
| Symbol Alias | GR |
| Approved Name | nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) |
| Previous Name | nuclear receptor subfamily 3, group C, member 1 |
| Location | 5q31-q32 |
| Position | chr5:143277931-143435512, -1 |
| External Links |
HGNC: 7978 Entrez Gene: 2908 Ensembl: ENSG00000113580 UCSC: uc003lnb.3 |
| No. of Studies | 5 (Positive: 2; Negative: 3; trend: 0) |
| Overlap with SZ? | YES |
| Overlap with MDD? | YES |
Gene related studies (count: 5)
| Reference | Tested Markers | Statistical Values/Author Comments | Result Category | Comment on Study |
|---|---|---|---|---|
| Spijker, A. T.,2009 | SNP: rs10052957, rs6198 | A trend was found for a protective effect of the exon 9beta polymorphism (p = 0.14) and the TthIIII polymorphism (p < 0.05) on the manifestation of the disease.We conclude that the exon 9b polymorphism and the TthIIII polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. | Positive | Comment on Study |
| Ceulemans, S.,2011 | SNP: rs10041520, rs10482616, rs10482633, rs10482668, rs10482672, rs10482682, rs10482689, rs10482704, rs10515522, rs17100236, rs17100289, rs17100306, rs17209237, rs17209258, rs17399352, rs1866388, rs2121152, rs258750, rs2963155, rs33389, rs4128753, rs4607376, rs4912911, rs6196, rs6877893, rs7701443, rs7705497, rs7709864, rs7714402, rs7720743, rs7728928, rs9324918, rs9324921, rs9324924 Other variant: rs6195 |
This study contributes to the growing evidence for a role of the glucocorticoid receptor gene (NR3C1) in vulnerability to mood disorders, and BPD in particular, and warrants further in vitro investigation of the at-risk haplotypes with respect to disease etiology. | Positive | Comment on Study |
| Szczepankiewicz, A.,2011 | SNP: rs10052957, rs258813, rs33388, rs41423247, rs6191, rs6196, rs6198 Other variant: rs6195 |
Genotype and allele frequency distributions did not differ significantly between BD patients and controls. | Negative | Comment on Study |
| Leszczynska-Rodziewicz, A., 2012 | SNP: rs10052957, rs258813, rs33388, rs41423247, rs6191, rs6196, rs6198 Other variant: rs6195 |
We did not find any association between the polymorphisms of the NR3C1 gene. | Negative | Comment on Study |
| Leszczynska-Rodziewicz A, 2013 | SNP: rs41423247, rs56149945, rs10052957, rs6198, rs6191, rs258813, rs6196, rs33388 | In our study we found no association between melancholic depression and polymorphisms in this gene. | Negative | Comment on Study |
Gene functional annotation
Gene related GO terms (count: 35)
GO terms by PBA (count: 4)
| ID | Name | Type | Evidence[PMID] | No. of Genes in BDgene |
|---|---|---|---|---|
| GO:0016020 | membrane | cellular component | IEA | 137 |
| GO:0003700 | sequence-specific DNA binding transcription factor activity | molecular function | IDA[15769988] | 66 |
| GO:0005496 | steroid binding | molecular function | IDA[15769988] | 4 |
| GO:0005634 | nucleus | cellular component | IDA[15769988] | 283 |
GO terms by database search (count: 31)
Gene related KEGG pathways (count: 1)
KEGG pathways by PBA (count: 0)
KEGG pathways by database search (count: 1)
| ID | Name | No. of Genes in BDgene | Brief Description |
|---|---|---|---|
| hsa04080 | Neuroactive ligand-receptor interaction | 92 |
Gene related BioCarta pathways (count: 3)
BioCarta pathways by PBA (count: 0)
BioCarta pathways by database search (count: 3)
| ID | Name | No. of Genes in BDgene | Brief Description |
|---|---|---|---|
| nthiPathway | NFkB activation by Nontypeable Hemophilus influenzae | 5 | |
| vobesityPathway | Visceral Fat Deposits and the Metabolic Syndrome | 2 | |
| gcrPathway | Corticosteroids and cardioprotection | 9 |
Gene related interactors from protein-protein interactions data in HPRD (count: 79)
| Gene | Interactor | Interactor in BDgene? | Experiment Type | PMID |
|---|---|---|---|---|
| NR3C1 | SUMO4 | NO | in vivo | 16236267 |
| NR3C1 | SMARCD1 | NO | in vitro;in vivo | 12917342 |
| NR3C1 | MAPK1 | NO | in vitro;in vivo | 12351702 , 9199329 |
| NR3C1 | NFKB1 | NO | in vitro | 7823959 , 8290595 |
| NR3C1 | PPARGC1A | NO | in vitro | 10713165 |
| NR3C1 | DDX54 | NO | in vitro | 12466272 |
| NR3C1 | FKBP4 | NO | in vitro | 8341706 |
| NR3C1 | CALR | NO | in vivo | 8107808 , 9089287 |
| NR3C1 | SMARCA4 | NO | in vitro | 9590696 |
| NR3C1 | ECD | NO | yeast 2-hybrid | 9928932 |
| NR3C1 | UBB | NO | in vivo | 11146632 |
| NR3C1 | TBP | YES | in vivo | 9649342 |
| NR3C1 | MAPK15 | NO | yeast 2-hybrid | 16624805 |
| NR3C1 | RAF1 | NO | in vivo | 11005817 |
| NR3C1 | MAPK8 | NO | in vitro;in vivo | 12351702 , 9199329 |
| NR3C1 | POU1F1 | NO | in vitro | 9426156 |
| NR3C1 | JUN | NO | in vitro;in vivo | 8733011 , 7823959 |
| NR3C1 | BAG1 | NO | in vitro;in vivo | 9603979 , 11101523 , 10477749 |
| NR3C1 | UBE2I | NO | in vitro;yeast 2-hybrid | 11812797 |
| NR3C1 | CALM1 | NO | in vitro;in vivo | 7887964 |
| NR3C1 | SFN | NO | yeast 2-hybrid | 12730237 |
| NR3C1 | KDM5A | NO | in vitro | 11358960 |
| NR3C1 | RELA | NO | in vitro;in vivo | 10995388 , 7659084 , 8290595 |
| NR3C1 | SYT1 | NO | in vivo;yeast 2-hybrid | 16143103 |
| NR3C1 | DAP3 | NO | in vitro;in vivo;yeast 2-hybrid | 12099703 , 10903152 |
| NR3C1 | COPS6 | NO | in vitro | 12237292 |
| NR3C1 | PBX1 | NO | in vivo | 12487626 |
| NR3C1 | PRKACA | NO | in vitro;in vivo | 11027313 |
| NR3C1 | PRPF6 | NO | in vivo | 12039962 |
| NR3C1 | ONECUT1 | NO | in vitro | 10430878 |
| NR3C1 | PRKDC | NO | in vitro | 9038175 |
| NR3C1 | TGFB1I1 | NO | yeast 2-hybrid | 10848625 |
| NR3C1 | LCK | NO | in vivo | 16888650 |
| NR3C1 | NCOR1 | NO | in vitro;in vivo | 12011091 |
| NR3C1 | SMARCE1 | NO | in vitro;in vivo | 12917342 |
| NR3C1 | TXN | NO | in vitro | 9915858 |
| NR3C1 | SUMO1 | NO | in vivo | 12193561 , 12144530 |
| NR3C1 | PTMS | NO | in vitro | 10601862 |
| NR3C1 | NCL | YES | in vitro;in vivo | 11162542 , 8530516 |
| NR3C1 | CHD9 | NO | in vitro;in vivo | 16523501 |
| NR3C1 | AR | NO | in vitro;yeast 2-hybrid | 9162033 |
| NR3C1 | TRIM28 | NO | in vitro;in vivo | 9742105 |
| NR3C1 | IDE | NO | in vivo | 8051160 |
| NR3C1 | ETS2 | NO | in vitro;in vivo | 11279115 |
| NR3C1 | SLC25A4 | YES | in vivo | 12039962 |
| NR3C1 | POU2F1 | NO | in vitro;in vivo | 10490647 , 10480874 , 9584182 , 14522952 , 11096094 |
| NR3C1 | SMARCA2 | NO | in vivo | 8223438 |
| NR3C1 | ETS1 | NO | in vitro | 11279115 |
| NR3C1 | NR2F2 | NO | in vitro;in vivo;yeast 2-hybrid | 14739255 |
| NR3C1 | NFKB2 | NO | in vitro;in vivo | 7823959 |
| NR3C1 | HSP90AA1 | YES | in vitro | 8898375 , 9334248 , 8645634 , 10066374 , 8621522 |
| NR3C1 | NCOA6 | YES | yeast 2-hybrid | 10866662 |
| NR3C1 | KPNA2 | NO | in vivo | 12933681 |
| NR3C1 | SMAD3 | NO | in vitro;in vivo | 12902338 , 10518526 |
| NR3C1 | TSG101 | NO | yeast 2-hybrid | 10508170 |
| NR3C1 | STAT3 | NO | in vivo | 14522952 , 9388192 |
| NR3C1 | NR2F6 | NO | in vitro | 10713182 |
| NR3C1 | HSPA1A | YES | in vivo | 12093808 |
| NR3C1 | NCOA2 | NO | in vitro | 12151000 |
| NR3C1 | TP53 | NO | in vitro;in vivo | 11080152 |
| NR3C1 | NCOA1 | NO | in vitro;yeast 2-hybrid | 12917342 , 12118039 , 12569182 |
| NR3C1 | RNF14 | NO | in vitro;in vivo | 10085091 |
| NR3C1 | POU2F2 | YES | in vitro | 10490647 , 10480874 , 9584182 |
| NR3C1 | PTGES3 | NO | in vivo | 10691735 |
| NR3C1 | MDM2 | NO | in vivo | 11562347 |
| NR3C1 | PSMC3IP | NO | in vitro;in vivo;yeast 2-hybrid | 11739747 |
| NR3C1 | ZBTB16 | NO | in vitro | 14521715 |
| NR3C1 | ADA | NO | in vitro | 9154805 |
| NR3C1 | HNRNPU | NO | in vivo | 9353307 |
| NR3C1 | MED14 | NO | in vitro;yeast 2-hybrid | 10508170 |
| NR3C1 | IFNGR2 | NO | in vitro | 8349631 |
| NR3C1 | RARA | NO | yeast 2-hybrid | 17641689 |
| NR3C1 | CEBPB | NO | in vitro;in vivo | 9817600 |
| NR3C1 | STAT5A | NO | in vitro;in vivo | 9528750 |
| NR3C1 | STAT5B | NO | in vitro;in vivo | 11158330 , 8878484 , 9528750 |
| NR3C1 | SMARCC1 | NO | in vitro | 9590696 |
| NR3C1 | PELP1 | NO | in vitro | 12415108 |
| NR3C1 | CEBPA | NO | in vitro;in vivo | 11818365 |
| NR3C1 | SMARCB1 | NO | in vitro;in vivo | 10688647 |
Related other genetic factors
Gene related SNPs (count: 83)
Literature-origin SNPs (count: 41)
| rs_ID | Location | Functional Annotation | No. of Studies (Positive/Negative/Trend)  |
|---|---|---|---|
| rs10482672 | chr5:143312968 - 143312968(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs33389 | chr5:143320934 - 143320934(1) | intron_variant; non_coding_transcript_variant | 1(1/0/0) |
| rs10052957 | chr5:143407136 - 143407136(1) | downstream_gene_variant; intron_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant; upstream_gene_variant | 4(1/3/0) |
| rs4128753 | chr5:143447227 - 143447227(1) | 1(0/1/0) | |
| rs6198 | chr5:143278056 - 143278056(1) | 3_prime_UTR_variant; downstream_gene_variant | 4(0/4/0) |
| rs56149945 | chr5:143399752 - 143399752(1) | downstream_gene_variant; missense_variant | 1(0/1/0) |
| rs1866388 | chr5:143380220 - 143380220(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | 1(0/1/0) |
| rs10041520 | chr5:143397119 - 143397119(1) | downstream_gene_variant; intron_variant | 1(0/1/0) |
| rs6877893 | chr5:143347628 - 143347628(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs10482689 | chr5:143296258 - 143296258(1) | downstream_gene_variant; intron_variant | 1(1/0/0) |
| rs7701443 | chr5:143413085 - 143413085(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs9324918 | chr5:143387595 - 143387595(1) | intron_variant; non_coding_transcript_variant | 1(1/0/0) |
| rs6196 | chr5:143281925 - 143281925(1) | intron_variant; synonymous_variant | 4(1/3/0) |
| rs33388 | chr5:143317730 - 143317730(1) | intron_variant; non_coding_transcript_variant | 3(0/3/0) |
| rs7714402 | chr5:143472583 - 143472583(1) | 1(0/1/0) | |
| rs9324921 | chr5:143388175 - 143388175(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs7720743 | chr5:143445739 - 143445739(1) | 1(0/1/0) | |
| rs10482668 | chr5:143313762 - 143313762(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs17100236 | chr5:143341161 - 143341161(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs258813 | chr5:143295125 - 143295125(1) | intron_variant | 3(0/3/0) |
| rs7709864 | chr5:143443564 - 143443564(1) | 1(0/1/0) | |
| rs4912911 | chr5:143427467 - 143427467(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs9324924 | chr5:143412919 - 143412919(1) | intron_variant; non_coding_transcript_variant | 1(1/0/0) |
| rs7728928 | chr5:143472710 - 143472710(1) | 1(0/1/0) | |
| rs6191 | chr5:143278591 - 143278591(1) | 3_prime_UTR_variant; downstream_gene_variant | 3(0/3/0) |
| rs7705497 | chr5:143471877 - 143471877(1) | 1(0/1/0) | |
| rs10482704 | chr5:143282198 - 143282198(1) | intron_variant | 1(0/1/0) |
| rs17209237 | chr5:143277647 - 143277647(1) | downstream_gene_variant | 1(0/1/0) |
| rs4607376 | chr5:143416967 - 143416967(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs17209258 | chr5:143293832 - 143293832(1) | intron_variant | 1(0/1/0) |
| rs2963155 | chr5:143376439 - 143376439(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | 1(1/0/0) |
| rs10482616 | chr5:143402002 - 143402002(1) | intron_variant; upstream_gene_variant | 1(0/1/0) |
| rs17100306 | chr5:143469602 - 143469602(1) | 1(0/1/0) | |
| rs10482633 | chr5:143370968 - 143370968(1) | downstream_gene_variant; intron_variant; non_coding_transcript_variant | 1(1/0/0) |
| rs17399352 | chr5:143375125 - 143375125(1) | downstream_gene_variant; intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs41423247 | chr5:143399010 - 143399010(1) | downstream_gene_variant; intron_variant | 3(0/3/0) |
| rs10515522 | chr5:143378829 - 143378829(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | 1(0/1/0) |
| rs258750 | chr5:143282324 - 143282324(1) | intron_variant | 1(0/1/0) |
| rs2121152 | chr5:143472486 - 143472486(1) | 1(0/1/0) | |
| rs17100289 | chr5:143429077 - 143429077(1) | intron_variant; non_coding_transcript_variant | 1(0/1/0) |
| rs10482682 | chr5:143299832 - 143299832(1) | downstream_gene_variant; intron_variant | 1(1/0/0) |
LD-proxies (count: 42)
| rs_ID | Literature-origin SNPs with LD | Location | Functional Annotation |
|---|---|---|---|
| rs258747 | chr5:143277248 - 143277248(1) | downstream_gene_variant | |
| rs852980 | chr5:143321291 - 143321291(1) | intron_variant; non_coding_transcript_variant | |
| rs4634384 | chr5:143401132 - 143401132(1) | intron_variant; upstream_gene_variant | |
| rs33383 | chr5:143330421 - 143330421(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | |
| rs4912913 | chr5:143438741 - 143438741(1) | upstream_gene_variant | |
| rs2918415 | chr5:143365398 - 143365398(1) | intron_variant; non_coding_transcript_variant | |
| rs11740792 | chr5:143367755 - 143367755(1) | intron_variant; non_coding_transcript_variant | |
| rs1438732 | chr5:143376701 - 143376701(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | |
| rs4128428 | chr5:143382248 - 143382248(1) | intron_variant; non_coding_transcript_variant | |
| rs2963151 | chr5:143354586 - 143354586(1) | intron_variant; non_coding_transcript_variant | |
| rs2963154 | chr5:143362972 - 143362972(1) | intron_variant; non_coding_transcript_variant | |
| rs2918419 | chr5:143342788 - 143342788(1) | intron_variant; non_coding_transcript_variant | |
| rs2918418 | chr5:143343808 - 143343808(1) | intron_variant; non_coding_transcript_variant | |
| rs852978 | chr5:143311031 - 143311031(1) | intron_variant; non_coding_transcript_variant | |
| rs258748 | chr5:143276889 - 143276889(1) | downstream_gene_variant | |
| rs10482642 | chr5:143348466 - 143348466(1) | intron_variant; non_coding_transcript_variant | |
| rs17287758 | chr5:143277456 - 143277456(1) | downstream_gene_variant | |
| rs17339831 | chr5:143364527 - 143364527(1) | intron_variant; non_coding_transcript_variant | |
| rs10515521 | chr5:143360601 - 143360601(1) | intron_variant; non_coding_transcript_variant | |
| rs11745958 | chr5:143336792 - 143336792(1) | downstream_gene_variant; intron_variant; non_coding_transcript_variant | |
| rs9324916 | chr5:143343095 - 143343095(1) | intron_variant; non_coding_transcript_variant | |
| rs10482655 | chr5:143326330 - 143326330(1) | intron_variant; non_coding_transcript_variant | |
| rs17339455 | chr5:143330158 - 143330158(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | |
| rs11750172 | chr5:143292096 - 143292096(1) | intron_variant | |
| rs4986593 | chr5:143314281 - 143314281(1) | intron_variant; non_coding_transcript_variant | |
| rs17209251 | chr5:143289658 - 143289658(1) | intron_variant | |
| rs2963156 | chr5:143378931 - 143378931(1) | intron_variant; non_coding_transcript_variant; upstream_gene_variant | |
| rs10482634 | chr5:143370884 - 143370884(1) | downstream_gene_variant; intron_variant; non_coding_transcript_variant | |
| rs852982 | chr5:143325856 - 143325856(1) | intron_variant; non_coding_transcript_variant | |
| rs17287745 | chr5:143275450 - 143275450(1) | downstream_gene_variant | |
| rs860457 | chr5:143308758 - 143308758(1) | intron_variant; non_coding_transcript_variant | |
| rs852977 | chr5:143307929 - 143307929(1) | intron_variant; non_coding_transcript_variant | |
| rs6188 | chr5:143300779 - 143300779(1) | intron_variant; non_coding_transcript_variant | |
| rs1837262 | chr5:143381962 - 143381962(1) | intron_variant; non_coding_transcript_variant | |
| rs2918416 | chr5:143361462 - 143361462(1) | intron_variant; non_coding_transcript_variant | |
| rs2918417 | chr5:143346605 - 143346605(1) | intron_variant; non_coding_transcript_variant | |
| rs2963149 | chr5:143345519 - 143345519(1) | intron_variant; non_coding_transcript_variant | |
| rs4912910 | chr5:143427325 - 143427325(1) | intron_variant; non_coding_transcript_variant | |
| rs12054797 | chr5:143426337 - 143426337(1) | intron_variant; non_coding_transcript_variant | |
| rs10477211 | chr5:143426309 - 143426309(1) | intron_variant; non_coding_transcript_variant | |
| rs190488 | chr5:143290743 - 143290743(1) | intron_variant | |
| rs12655166 | chr5:143429707 - 143429707(1) | intron_variant; non_coding_transcript_variant |
Gene related CNVs (count: 0)
Gene related other variants (count: 1)
| Variant Name | Variant Type | Location in Gene | No. of Studies (Positive/Negative/Trend) |
|---|---|---|---|
| rs6195 | point mutation | 3 (0/3/0) |
Gene related regions (count: 2)
| Region Name | Position | No. of Studies (Positive/Negative/Trend) |
|---|---|---|
| Chr 5 | chr5:0-181538259 | 3 (0/2/1) |
| 5q31-q33 | chr5:131200000-160500000 | 1 (1/0/0) |
Overlap with schizophrenia (SZ) and major depressive disorder (MDD)
Gene relationship with SZ
Overlap with SZ from cross-disorder studies (count: 0)
Overlap with SZ from candidate gene intersection analysis (count: 1)
Gene relationship with MDD
Overlap with MDD from cross-disorder studies (count: 0)
Overlap with MDD from candidate gene intersection analysis (count: 8)
| Reference | Description | Category in MDD | Link in MK4MDD |
|---|---|---|---|
| 16458268 | 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. | Pos | NR3C1 |
| 21764460 | We have found three polymorphisms (rs6198, rs6191 and rs33388) to be associated with major depressive disorder (MDD) | Pos | NR3C1 |
| 19782477 | 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 | Pos | NR3C1 |
| 24424390 | Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls | Pos | NR3C1 |
| 16580345 | Homozygous carriers of the BclI polymorphism and ER22/23EK-carriers had an increased risk of developing a major depressive episode. | Pos | NR3C1 |
| 18286599 | 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 | Pos | NR3C1 |
| 21195417 | 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) | Pos | NR3C1 |
| 16192984 | 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. | Pos | NR3C1 |
View in gBrowse
Region: chr5:143277931..143435512 View in gBrowse
Copyright: Bioinformatics Lab, Institute of Psychology, Chinese Academy of Sciences Feedback
Acknowledgements
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Last update: March 31, 2016