NR3C1
Nuclear Receptor Subfamily 3 Group C Member 1 (Glucocorticoid Receptor)
Gene Information Card
| Symbol | NR3C1 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 3 Group C Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q31.3 |
| NCBI Gene ID | 2908 ncbi.nlm.nih.gov/gene/2908 |
| Ensembl ID | ENSG00000113580 |
| UniProt ID | P04150 |
| OMIM ID | 138040 |
| HGNC ID | 7978 |
| Aliases | GR, GCR, GRL, GRIP1, GRL1, NR3C1 |
Description
The NR3C1 gene encodes the glucocorticoid receptor (GR), a nuclear receptor transcription factor that binds glucocorticoids such as cortisol. Upon ligand binding, GR translocates to the nucleus and regulates the expression of target genes involved in metabolism, inflammation, immune response, and stress adaptation. Alternative splicing and translational isoforms produce multiple receptor variants with distinct tissue-specific functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Glucocorticoid resistance (Chrousos syndrome) | Loss-of-function mutations in NR3C1 impair cortisol binding or transactivation, leading to compensatory ACTH elevation and adrenal hyperandrogenism. | OMIM #138040; ClinVar |
| Cushing syndrome (primary) | Somatic gain-of-function mutations or overexpression of NR3C1 can enhance glucocorticoid signaling, contributing to metabolic syndrome features. | COSMIC; literature |
| Major depressive disorder | Altered NR3C1 expression and methylation patterns are associated with HPA axis dysregulation and stress response. | NCBI Gene; PubMed |
| Inflammatory bowel disease | Polymorphisms in NR3C1 influence glucocorticoid sensitivity and treatment response. | ClinVar; GWAS catalog |
| Acute lymphoblastic leukemia | NR3C1 mutations (e.g., R477H) confer glucocorticoid resistance, affecting therapy outcome. | COSMIC; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Adrenal gland | 12.5 | Medium |
| Liver | 8.3 | Medium |
| Lung | 6.1 | Low |
| Brain (cortex) | 5.4 | Low |
| Heart | 4.2 | Low |
| Kidney | 7.8 | Medium |
| Skeletal muscle | 3.1 | Low |
| Spleen | 9.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression; commonly used for functional studies |
| HeLa | 11.5 | High expression; cervical cancer line |
| A549 | 8.7 | Medium expression; lung carcinoma |
| K562 | 6.3 | Low expression; leukemia line |
| HepG2 | 9.8 | Medium expression; hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R477H | Missense | <0.1% | Reduces ligand binding and transactivation; associated with glucocorticoid resistance |
| D641V | Missense | <0.1% | Impairs nuclear translocation; dominant negative effect |
| I559N | Missense | <0.1% | Loss of function; familial glucocorticoid resistance |
| c.2310+1G>A | Splice site | <0.1% | Exon skipping; truncated protein; loss of function |
| T556I | Missense | <0.1% | Reduced affinity for cortisol; partial resistance |
Mutation functional classification
Loss of Function (LOF)
Mutations that impair ligand binding, nuclear translocation, or DNA binding (e.g., R477H, D641V, I559N) lead to glucocorticoid resistance and compensatory HPA axis activation.
Gain of Function (GOF)
Somatic mutations or amplifications that enhance GR activity are rare but may contribute to metabolic disorders and Cushing syndrome features.
Dominant Negative (DN)
Certain missense mutations (e.g., D641V) produce receptors that interfere with wild-type GR function, reducing overall glucocorticoid signaling.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Glucocorticoid receptor signaling pathway (Reactome R-HSA-3371497)
• Glucocorticoid receptor regulatory network (WikiPathways WP288)
• NR3C1 signaling in inflammation (KEGG hsa04934)
Protein Summary
The glucocorticoid receptor (GR) encoded by NR3C1 is a 777-amino acid protein with an N-terminal transactivation domain, a central DNA-binding domain with two zinc fingers, and a C-terminal ligand-binding domain. GR functions as a homodimer that binds glucocorticoid response elements (GREs) in target gene promoters. It also interacts with other transcription factors (e.g., NF-κB, AP-1) to mediate anti-inflammatory effects. Post-translational modifications including phosphorylation and sumoylation modulate its activity and stability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR3C1 Knockout HEK293 Cell Line | EDJ-KQ14493 | Human | 2908 | Details Get a Quote |
| NR3C1 Knockout A-549 Cell Line | EDJ-KQ44755 | Human | 2908 | Details Get a Quote |
| NR3C1 Knockout HCT 116 Cell Line | EDJ-KQ44756 | Human | 2908 | Details Get a Quote |
| NR3C1 Knockout HeLa Cell Line | EDJ-KQ44757 | Human | 2908 | Details Get a Quote |
| NR3C1 Knockout TCCSUP Cell Line | EDJ-KZ377 | Human | 2908 | Details Get a Quote |
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