NR3C2 (Mineralocorticoid Receptor)
Nuclear Receptor Subfamily 3 Group C Member 2: Key Regulator of Electrolyte and Blood Pressure Homeostasis
Gene Information Card
| Symbol | NR3C2 |
|---|---|
| Full Name | Nuclear Receptor Subfamily 3 Group C Member 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.23 |
| NCBI Gene ID | 4306 ncbi.nlm.nih.gov/gene/4306 |
| Ensembl ID | ENSG00000151623 |
| UniProt ID | P08235 |
| OMIM ID | 600983 |
| HGNC ID | 7979 |
| Aliases | MR, MCR, MLR, NR3C2V1, NR3C2V2 |
Description
The NR3C2 gene encodes the mineralocorticoid receptor (MR), a ligand-activated transcription factor belonging to the nuclear receptor superfamily. MR binds aldosterone and, to a lesser extent, cortisol, regulating the expression of genes involved in sodium reabsorption, potassium excretion, and water homeostasis in epithelial tissues (kidney, colon, sweat glands). It also plays roles in non-epithelial tissues such as the heart, brain, and adipose tissue, influencing cardiovascular function, inflammation, and cognition. Mutations in NR3C2 cause autosomal dominant pseudohypoaldosteronism type 1 (PHA1) and are associated with early-onset hypertension and pregnancy-induced hypertension.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Pseudohypoaldosteronism type 1 (PHA1), autosomal dominant | Loss-of-function mutations in NR3C2 impair aldosterone signaling, leading to renal salt wasting, hyperkalemia, and metabolic acidosis despite high aldosterone levels. | ClinVar, OMIM #600983 |
| Early-onset hypertension (with exacerbation in pregnancy) | Gain-of-function or missense mutations (e.g., S810L) alter ligand specificity, allowing progesterone and other steroids to activate MR, causing sodium retention and hypertension. | OMIM #605115, ClinVar |
| Primary aldosteronism (Conn syndrome) | Somatic mutations or altered MR expression in adrenal adenomas contribute to aldosterone excess and hypertension. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 18.5 | High |
| Colon | 12.3 | Medium |
| Salivary gland | 9.8 | Medium |
| Heart | 6.2 | Medium |
| Brain (hippocampus) | 4.1 | Low |
| Adipose tissue | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK 293 | 15.2 | High expression in transfected cells |
| HCT116 | 8.7 | Colorectal carcinoma line |
| MCF7 | 5.4 | Breast cancer line |
| HepG2 | 2.1 | Hepatocellular carcinoma line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| S810L | Missense | Rare | Gain-of-function: alters ligand specificity, enabling progesterone and cortisol to activate MR, causing early-onset hypertension. |
| c.2159G>A (p.Arg720Gln) | Missense | Rare | Loss-of-function: associated with autosomal dominant PHA1. |
| c.2881C>T (p.Arg961*) | Nonsense | Rare | Loss-of-function: premature stop codon leading to truncated, non-functional MR in PHA1. |
Mutation functional classification
Loss of Function (LOF)
Mutations that reduce or abolish MR transcriptional activity (e.g., nonsense, frameshift, missense in DNA-binding or ligand-binding domains) cause autosomal dominant pseudohypoaldosteronism type 1.
Gain of Function (GOF)
Missense mutations (e.g., S810L) that broaden ligand specificity or increase constitutive activity lead to early-onset hypertension and pregnancy-associated hypertension.
Dominant Negative (DN)
Some missense mutations in the ligand-binding domain may exert dominant-negative effects by forming inactive heterodimers with wild-type MR, contributing to PHA1.
View complete mutation data：
Gene Ontology (GO)
| • GO:0003707 (steroid hormone receptor activity) | • GO:0004879 (nuclear receptor activity) |
| • GO:0005515 (protein binding) | • GO:0008270 (zinc ion binding) |
| • GO:0042809 (vitamin D receptor binding) | • GO:0006355 (regulation of transcription |
| • DNA-templated) | • GO:0006357 (regulation of transcription by RNA polymerase II) |
| • GO:0030522 (intracellular receptor signaling pathway) | • GO:0050482 (arachidonic acid secretion) |
| • GO:0071392 (cellular response to steroid hormone stimulus) |
Pathways
• Mineralocorticoid receptor signaling pathway (Reactome: R-HSA-383280)
• Aldosterone-regulated sodium reabsorption (KEGG: hsa04960)
• Nuclear receptor transcription pathway (WikiPathways: WP287)
Protein Summary
The mineralocorticoid receptor (MR) is a 984-amino-acid protein with a conserved nuclear receptor structure: an N-terminal domain, a DNA-binding domain (two zinc fingers), a hinge region, and a C-terminal ligand-binding domain. In the absence of ligand, MR resides in the cytoplasm complexed with heat shock proteins. Upon aldosterone binding, MR translocates to the nucleus, homodimerizes, and binds to hormone response elements (HREs) on DNA to regulate target genes such as SCNN1A (ENaC subunit), SGK1, and KCNJ16. MR also interacts with coactivators (e.g., NCOA2) and corepressors (e.g., NCOR1). Post-translational modifications include phosphorylation, sumoylation, and ubiquitination, which modulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NR3C2 Knockout HEK293 Cell Line | EDJ-KQ5218 | Human | 4306 | Details Get a Quote |
| NR3C2 Knockout HeLa Cell Line | EDJ-KQ53879 | Human | 4306 | Details Get a Quote |
| NR3C2 Knockout A-549 Cell Line | EDJ-KQ62370 | Human | 4306 | Details Get a Quote |
| NR3C2 Knockout HCT 116 Cell Line | EDJ-KQ70839 | Human | 4306 | Details Get a Quote |
| NR3C2 Knockout HAP1 Cell Line | EDC08013 | Human | 4306 | Details Get a Quote |
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