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Symbol NR3C1 contributors: mct/npt - updated : 10-05-2016
HGNC name nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor)
HGNC id 7978
Corresponding disease
GRL cortisol resistance, primary
Location 5q31.3      Physical location : 142.657.496 - 142.815.077
Synonym name glucocorticoid receptor
Synonym symbol(s) GR, GCR, GRL, GCCR
TYPE functioning gene
STRUCTURE 455.83 kb     9 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked Y status confirmed
Map see ADRB2 ,CSF1R
Physical map
DIAPH1 5q31-q32 diaphanous homolog 1 (Drosophila) HDAC3 5q31.3 histone deacetylase 3 FLJ90583 FLJ00007 5q31.3 hypothetical protein FLJ00007 ARAP3 5q31.3 ARF-GAP, RHO-GAP, ankyrin repeat and plekstrin homology domains-containing protein 3 PCDH1 5q31-q32 protocadherin 1 (cadherin-like 1) LOC285615 5q31.3 similar to dJ702J19.1 (glycine cleavage system protein H (aminomethyl carrier)) KIAA0141 5q31.3 similar to dJ702J19.1 (glycine cleavage system protein H (aminomethyl carrier)) PCDH12 5q31.3 protocadherin 12 RNF14 5q23.3-q31.1 ring finger protein 14 GNPDA1 5q21 glucosamine-6-phosphate deaminase 1 MRPL11P2 5q31.3 glucosamine-6-phosphate deaminase 1 NDFIP1 5q31.3 Nedd4 family interacting protein 1 SPRY4 5q31.3 sprouty homolog 4 (Drosophila) FGF1 5q31.3 fibroblast growth factor 1 (acidic) GRAF 5q31 fibroblast growth factor 1 (acidic) NR3C1 5q31.3 nuclear receptor subfamily 3, group C, member 1 (glucocorticoid receptor) LOC389335 5 LOC389335 LOC345537 5q32 similar to hypothetical protein HB-1 5q32 minor histocompatibility antigen HB-1 SMAP-5 5q32 golgi membrane protein SB140 KIAA1317 5q32 KIAA1317 protein
TRANSCRIPTS type messenger
text seven spliced variants : five encoding for isoform Alpha, one for isoform BÍta and one for isoform Gamma
  • 11 splice variants of the hGR exon 1, based on seven exon 1s, and four (1-D to 1-F and 1-H)
  • identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    9 splicing 7286 85 777 - 2007 17438138
  • containing exon 1a (longer than 1b & 1c)
  • containing exon 5b (shorter than 5a)
  • containing exon 11a (longer than 11b)
  • lacking exons 2 & 3
  • longest transcript
  • variant 1 encoding the isoform Alpha
  • 9 splicing 6614 85 777 - 2007 17438138
  • containing exon 1b
  • containing exon 5b (shorter than 5a)
  • containing exon 11a (longer than 11b)
  • lacking exons 2 & 3
  • variant 2 encoding the isoform Alpha
  • 9 splicing 6517 85 777 - 2007 17438138
  • containing exon 1c (shorter than 1a & 1b)
  • containing exon 5b (shorter than 5a)
  • containing exon 11a (longer than 11b)
  • lacking exons 2 & 3
  • variant 3 encoding the isoform Alpha
  • 9 splicing 6410 85 777 - 2007 17438138
  • containing exon 5b (shorter than 5a)
  • containing exon 11a (longer than 11b)
  • lacking exons 1 & 3
  • variant 4 encoding the isoform Alpha
  • 9 splicing 6784 85 777 - 2007 17438138
  • containing exon 5b (shorter than 5a)
  • containing exon 11a (longer than 11b)
  • lacking exons 1 & 2
  • variant 5 encoding the isoform Alpha
  • 9 splicing 4154 81 742 - 2007 17438138
  • containing exon 5b (shorter than 5a)
  • containing exon 11b (shorter than 11a)
  • lacking exons 1 & 2
  • encoding the isoform Beta
  • influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRalpha-mediated transcriptional activity
  • 9 splicing 6787 85 778 - 2007 17438138
  • containing exon 5a (longer than 5b)
  • containing exon 11a (longer than 11b)
  • lacking exons 1 & 2
  • encoding for the isoform Gamma
  • - - 547 - 145 - 2007 17438138
    9 - 6801 - 680 - 2007 17438138
  • variant 1C3, alpha-C3, also known as GR-C3
  • 9 - 6802 - 688 - 2007 17438138
  • variant 1C2, alpha-C2, also known as GR-C2
  • 9 - 6801 - 692 - 2007 17438138
  • alpha-C1, also known as GR-C1
  • - - 585 - 145 in the hippocampus, also detected in the immune system, in the liver, lung and smooth muscle 2007 17438138
    - - 511 - - in the hippocampus, also detected in the immune system 2007 17438138
    - - 498 - 145 in the hippocampus, also detected in the immune system 2007 17438138
    9 - 6801 - 462 only in the hippocampus 2007 17438138
    variant 1D, alpha-D1, also known as GR-D1
    9 - 6801 - 751 - 2007 17438138
  • alpha-B, also known as GR-B
  • 9 - 6801 - 447 - 2007 17438138
  • alpha-D2, also known as GR-D2)
  • 9 - 6801 - 442 - 2007 17438138
    alpha-D3, also known as GR-D3
    - - 4104 - 676 - 2007 17438138
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularvessel   highly
    Digestiveesophagus   moderately
    Endocrinepancreas   moderately
     parathyroid   moderately
    Lymphoid/Immunelymph node   highly
    Nervousbrainlimbic systemhippocampus predominantly Homo sapiens
     nervecranial nerve  moderately
    Reproductivefemale systemplacenta  moderately
     male systemtestis  moderately
    Urinarykidney   moderately
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose  highly
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, pregnancy
    Text placenta, embryonic tissue
  • receptor composed of a N terminal modulator domain
  • a hinge region homologous only with those of the oxosteroid receptors
  • a central bipartite zinc finger DNA binding domain followed by a nuclear localization signal (NLS)
  • activation function 1 (AF1) in the N-terminal half of NR3C1
  • C terminal ligand binding domain including a transactivation and dimerization domain (important in conferring transactivational activity), the AF2 domain in the C-terminal ligand-binding domain (LBD)
    interspecies homolog to rattus Nr3c1 (90.83 pc)
    homolog to murine Nr3c1 (90.44 pc)
  • nuclear hormone receptor family
  • NR3 subfamily
  • CATEGORY transcription factor , signaling hormone , receptor
    SUBCELLULAR LOCALIZATION     intracellular
    basic FUNCTION
  • nuclear hormone receptor that regulates multiple physiological and pathophysiological processes (Niu 2009)
  • inhibit erythroid maturation not only through a transcriptional mechanism, but also through a rapid membrane-associated pathway that interferes with EPO receptor signaling (Stellacci 2009)
  • regulates target genes by associating with specific DNA binding sites, the sequences of which differ between genes (Meijsing 2009)
  • coactivation of NR3C1 and NFKB alters signaling pathways that are regulated by each factor separately and provide insight into the networks underlying the NR3C1 and NFKB crosstalk
  • endothelial NR3C1 is a critical regulator of NFKB1 activation and nitric oxide synthesis in sepsis
  • in the brain, has been implicated, amongst others, in feedback regulation of the hypothalamic-pituitary-adrenal axis, with potential deficits during aging and in depression
  • is required for fetal heart maturation
  • ligand-dependent transcription factor of the nuclear receptor superfamily
  • NR3C1 -dependent repression of elongation-controlled genes was abolished specifically in negative elongation factor-deficient macrophages
  • both NR3C1 and FOXO1 are required for ANGPTL4 transcription activation, and FOXO1 negatively mediates the suppressive effect of insulin
  • CELLULAR PROCESS nucleotide, transcription, regulation
    signaling signal transduction
    a component
    small molecule
  • interacting with tissue-specific transcriptional activators required for receptor actin (see HNFS)
  • upregulating HIF1 gene expression under hypoxic conditions
  • transcriptional activity suppressed with association yoGbetagamma complexes
  • PMF1 binds to the glucocorticoid receptor (NR3C1), and represses glucocorticoid-induced transcription
  • ANGPTL4 is a direct target that participates in glucocorticoid-regulated triglyceride metabolism (Koliwad 2009)
  • interacting with SKA2 in cancer cells (Rice 2008)
  • NUP62 and NR3C1 were able to interact in a more efficient manner when chaperoned by the HSP90-based heterocomplex
  • role for GPR50 in NR3C1 signalling through interaction with kat5
  • FOXA1 is a potent enhancer of NR3C1-induced transcription
  • molecular interplay of NR3C1 and MEF2A in the control of genes important for neuronal plasticity
  • GSK3B is important for NR3C1 transactivation activity and GSK3B inhibition suppresses NR3C1-stimulated gene expression
  • FOXO3 is an immediate early glucocorticoid receptor (NR3C1) target, whose transcription is even further enhanced by conditions that mimic metabolic stress
  • AGRP is a common orexigenic target gene of NR3C1 and BSX
  • mutual antagonism between NR4A3 and NR3C1 to be a key rheostat for peripheral metabolic signals to centrally control energy balance
  • NR3C1-induced expression of HNF4A may likely contribute to indirect SLC22A1 gene up-regulation by dexamethasone in primary human hepatocytes, but not in hepatocyte-derived tumor cell lines
  • BUD23 is a novel regulator of chromatin structure affecting NR3C1 recruitment and function, contributing to loss of NR3C1 sensitivity in inflammation, with suppressed expression in pulmonary disease
  • NR1D1 influences the stability and nuclear localization of NR3C1
  • MDFIC is a binding partner for NR3C1, and NR3C1 directly represses the MDFIC gene, revealing a negative feedback loop by which glucocorticoids limit MDFIC activity
  • cell & other
    activated by ligand-induced activity of N3C1 is enhanced by DAP3
    Other phosphorylated by activated JNK (phosphorylates NR3C1 at Ser226, enhances its nuclear export after withdrawal of a ligand for NR3C1, dexamethasone, and may contribute to termination of NR3C1-mediated transcription) (Itoh 2002)
    GSK3B regulates NR3C1 response by genomic and nongenomic mechanisms
    corresponding disease(s) GRL
    related resource Glucocorticoid Receptor Resource database
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    NR3C1 gene inactivated through promoter hypermethylation in colorectal tumor development
    Variant & Polymorphism
    Candidate gene DNA methylation markers of Gastric cancer (GC), which may serve as useful markers that may identify a distinct subset of GC (Kang 2008)
    Therapy target