Mineralocorticoid receptor

The mineralocorticoid receptor (or MR, MLR, MCR), also known as the aldosterone receptor or nuclear receptor subfamily 3, group C, member 2, (NR3C2) is a protein that in humans is encoded by the NR3C2 gene that is located on chromosome 4q31.1-31.2.[5]

PBB Protein NR3C2 image.jpg
Available structures
PDBOrtholog search: PDBe RCSB
AliasesNR3C2, MCR, MLR, MR, NR3C2VIT, nuclear receptor subfamily 3 group C member 2
External IDsOMIM: 600983 MGI: 99459 HomoloGene: 121495 GeneCards: NR3C2
Gene location (Human)
Chromosome 4 (human)
Chr.Chromosome 4 (human)[1]
Chromosome 4 (human)
Genomic location for NR3C2
Genomic location for NR3C2
Band4q31.23Start148,078,762 bp[1]
End148,444,698 bp[1]
RNA expression pattern
PBB GE NR3C2 205259 at fs.png
More reference expression data
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 4: 148.08 – 148.44 MbChr 8: 76.9 – 77.25 Mb
PubMed search[3][4]
View/Edit HumanView/Edit Mouse

MR is a receptor with equal affinity for mineralocorticoids and glucocorticoids. It belongs to the nuclear receptor family where the ligand diffuses into cells, interacts with the receptor and results in a signal transduction affecting specific gene expression in the nucleus.


MR is expressed in many tissues, such as the kidney, colon, heart, central nervous system (hippocampus), brown adipose tissue and sweat glands. In epithelial tissues, its activation leads to the expression of proteins regulating ionic and water transports (mainly the epithelial sodium channel or ENaC, Na+/K+ pump, serum and glucocorticoid induced kinase or SGK1) resulting in the reabsorption of sodium, and as a consequence an increase in extracellular volume, increase in blood pressure, and an excretion of potassium to maintain a normal salt concentration in the body.

The receptor is activated by mineralocorticoids such as aldosterone and its precursor deoxycorticosterone as well as glucocorticoids, like cortisol. In intact animals, the mineralocorticoid receptor is "protected" from glucocorticoids by co-localization of an enzyme, corticosteroid 11-beta-dehydrogenase isozyme 2 (a.k.a. 11β-hydroxysteroid dehydrogenase 2; 11β-HSD2), that converts cortisol to inactive cortisone. It also responds to some progestins. Spironolactone and eplerenone are steroidal MR antagonists of the spirolactone group.

Activation of the mineralocorticoid receptor, upon the binding of its ligand aldosterone, results in its translocation to the cell nucleus, homodimerization and binding to hormone response elements present in the promoter of some genes. This results in the complex recruitment of the transcriptional machinery and the transcription into mRNA of the DNA sequence of the activated genes.[6]

An activating mutation in the NR3C2 gene (S810L) results in constitutive activity of the mineralocorticoid receptor, leading to severe early-onset hypertension that is exacerbated by pregnancy. In a family known to harbor the S810L mutation, 3 individuals carrying the mutation died of chronic heart failure before age 50.[7] Additional studies have shown that this activated version of MR can positively respond to ligands that are traditionally antagonists, such as endogenous hormones like progesterone, and the diuretic drugs spironolactone and eplerenone.[7]

Currently, the non-steroidal anti-mineralocorticoid drug Finerenone (Bayer) is in phase III clinical trials for the treatment of chronic heart failure.


Mineralocorticoid receptor has been shown to interact with:

See alsoEdit


  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000151623 - Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031618 - Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Fan YS, Eddy RL, Byers MG, Haley LL, Henry WM, Nowak NJ, Shows TB (1989). "The human mineralocorticoid receptor gene (MLR) is located on chromosome 4 at q31.2". Cytogenet. Cell Genet. 52 (1–2): 83–4. doi:10.1159/000132846. PMID 2558856.
  6. ^ Fuller PJ, Young MJ (2005). "Mechanisms of mineralocorticoid action". Hypertension. 46 (6): 1227–35. CiteSeerX doi:10.1161/01.HYP.0000193502.77417.17. PMID 16286565. S2CID 14749847.
  7. ^ a b Geller, D. S.; Farhi, A.; Pinkerton, N.; Fradley, M.; Moritz, M.; Spitzer, A.; Meinke, G.; Tsai, F. T.; Sigler, P. B. (2000-07-07). "Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy". Science. 289 (5476): 119–123. Bibcode:2000Sci...289..119G. doi:10.1126/science.289.5476.119. ISSN 0036-8075. PMID 10884226.
  8. ^ a b Savory JG, Préfontaine GG, Lamprecht C, Liao M, Walther RF, Lefebvre YA, Haché RJ (Feb 2001). "Glucocorticoid receptor homodimers and glucocorticoid-mineralocorticoid receptor heterodimers form in the cytoplasm through alternative dimerization interfaces". Mol. Cell. Biol. 21 (3): 781–93. doi:10.1128/MCB.21.3.781-793.2001. PMC 86670. PMID 11154266.
  9. ^ Zennaro MC, Souque A, Viengchareun S, Poisson E, Lombès M (September 2001). "A new human MR splice variant is a ligand-independent transactivator modulating corticosteroid action". Mol. Endocrinol. 15 (9): 1586–98. doi:10.1210/mend.15.9.0689. PMID 11518808.
  10. ^ Thénot S, Henriquet C, Rochefort H, Cavaillès V (May 1997). "Differential interaction of nuclear receptors with the putative human transcriptional coactivator hTIF1". J. Biol. Chem. 272 (18): 12062–8. doi:10.1074/jbc.272.18.12062. PMID 9115274.

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