NR3C1 (nuclear receptor subfamily 3 group C member 1) encodes for glucocorticoid receptor. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues (R). 

Glucocorticoid resistance can cause hypoglycemia, hypertension,fatigue, and anxiety (R). 

     From NCBI Gene: Glucocorticoid resistance, generalizedFrom UniProt: Glucocorticoid resistance, generalized (GCCR): An autosomal dominant disease characterized by increased plasma cortisol concentration and high urinary free cortisol, resistance to adrenal suppression by dexamethasone, and the absence of Cushing syndrome typical signs. Clinical features include hypoglycemia, hypertension, metabolic alkalosis, chronic fatigue and profound anxiety. [MIM:615962]

     From NCBI Gene: This gene encodes glucocorticoid receptor, which can function both as a transcription factor that binds to glucocorticoid response elements in the promoters of glucocorticoid responsive genes to activate their transcription, and as a regulator of other transcription factors. This receptor is typically found in the cytoplasm, but upon ligand binding, is transported into the nucleus. It is involved in inflammatory responses, cellular proliferation, and differentiation in target tissues. Mutations in this gene are associated with generalized glucocorticoid resistance. Alternative splicing of this gene results in transcript variants encoding either the same or different isoforms. Additional isoforms resulting from the use of alternate in-frame translation initiation sites have also been described, and shown to be functional, displaying diverse cytoplasm-to-nucleus trafficking patterns and distinct transcriptional activities (PMID:15866175). [provided by RefSeq, Feb 2011] From UniProt: Isoform Alpha-D3: Has lowest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Isoform Alpha-B: More effective than isoform Alpha in transcriptional activation, but not repression activity. Isoform Alpha-D1: Has transcriptional activation activity. Isoform Alpha: Has transcriptional activation and repression activity (PubMed:15866175, PubMed:19248771, PubMed:20484466, PubMed:23820903, PubMed:11435610, PubMed:15769988, PubMed:17635946, PubMed:19141540, PubMed:21664385). Mediates glucocorticoid-induced apoptosis (PubMed:23303127). Promotes accurate chromosome segregation during mitosis (PubMed:25847991). May act as a tumor suppressor (PubMed:25847991). May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic gene expression. Isoform Alpha-D2: Has transcriptional activation activity. Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Involved in chromatin remodeling (PubMed:9590696). Plays a role in rapid mRNA degradation by binding to the 5' UTR of target mRNAs and interacting with PNRC2 in a ligand-dependent manner which recruits the RNA helicase UPF1 and the mRNA-decapping enzyme DCP1A, leading to RNA decay (PubMed:25775514). Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Isoform Alpha-C1: Has transcriptional activation activity. Isoform 10: Has transcriptional activation activity. Isoform Alpha-C2: Has transcriptional activation activity. Isoform Beta: Acts as a dominant negative inhibitor of isoform Alpha (PubMed:7769088, PubMed:8621628, PubMed:20484466). Has intrinsic transcriptional activity independent of isoform Alpha when both isoforms are coexpressed (PubMed:19248771, PubMed:26711253). Loses this transcription modulator function on its own (PubMed:20484466). Has no hormone-binding activity (PubMed:8621628). May play a role in controlling glucose metabolism by maintaining insulin sensitivity (By similarity). Reduces hepatic gluconeogenesis through down-regulation of PEPCK in an isoform Alpha-dependent manner (PubMed:26711253). Directly regulates STAT1 expression in isoform Alpha-independent manner (PubMed:26711253). Isoform GR-P: Increases activity of isoform Alpha. Isoform Alpha-2: Has lower transcriptional activation activity than isoform Alpha. Exerts a dominant negative effect on isoform Alpha trans-repression mechanism (PubMed:20484466). Isoform Alpha-C3: Has highest transcriptional activation activity of all isoforms created by alternative initiation (PubMed:15866175, PubMed:23820903). Has transcriptional repression activity (PubMed:23303127). Mediates glucocorticoid-induced apoptosis (PubMed:23303127, PubMed:23820903).

The following transcription factors affect gene expression:

• p53
• Egr-1
• AP-1
• c-Jun
• HNF-4alpha1
• HNF-4alpha2
• Sp1
• c-Fos
• IRF-1
• p300

Tissue specificity:

Widely expressed including bone, stomach, lung, liver, colon, breast, ovary, pancreas and kidney (PubMed:25847991). In the heart, detected in left and right atria, left and right ventricles, aorta, apex, intraventricular septum, and atrioventricular node as well as whole adult and fetal heart (PubMed:10902803). Isoform Beta: Widely expressed including brain, bone marrow, thymus, spleen, liver, kidney, pancreas, lung, fat, skeletal muscle, heart, placenta and blood leukocytes (PubMed:7769088, PubMed:8621628). Isoform Alpha-2: Expressed at low level.

Induction:

Isoform Alpha: Up-regulated by TNF (at protein level). Isoform Beta: Up-regulated by TNF and becomes the predominant isoform which may lead to glucocorticoid resistance (at protein level).

Molecular Function:

• Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
• Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Rna Binding
• Glucocorticoid Receptor Activity
• Steroid Binding
• Zinc Ion Binding
• Protein Complex Binding
• Glucocorticoid-Activated Rna Polymerase Ii Transcription Factor Binding Transcription Factor Activity
• Steroid Hormone Binding

Biological Processes:

• Transcription, Dna-Templated
• Regulation Of Transcription, Dna-Templated
• Transcription From Rna Polymerase Ii Promoter
• Transcription Initiation From Rna Polymerase Ii Promoter
• Apoptotic Process
• Chromosome Segregation
• Mitotic Nuclear Division
• Signal Transduction
• Covalent Chromatin Modification
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Cell Division
• Cellular Response To Steroid Hormone Stimulus

Drug Bank:

• Alclometasone
• Clobetasol Propionate
• Flurandrenolide
• Fluticasone Propionate
• Halobetasol Propionate
• Hydrocortamate
• Loteprednol
• Mometasone
• Beclomethasone
• Betamethasone
• Ciclesonide
• Clocortolone
• Cortisone Acetate
• Desonide
• Desoximetasone
• Dexamethasone
• Difluprednate
• Fludrocortisone
• Flumethasone
• Flunisolide
• Fluocinolone Acetonide
• Fluocinonide
• Fluorometholone
• Fluoxymesterone
• Hydrocortisone
• Medrysone
• Megestrol Acetate
• Methylprednisolone
• Mifepristone
• Paramethasone
• Prednicarbate
• Prednisolone
• Prednisone
• Spironolactone
• Triamcinolone
• Ulipristal
• Amcinonide
• Budesonide
• Diflorasone
• Fluticasone Furoate
• Rimexolone