NR3C2 Gene

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This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/gene/nr3c2

nuclear receptor subfamily 3 group C member 2

genes

1. Introduction

The NR3C2 gene provides instructions for making a protein called the mineralocorticoid receptor. This protein is important in regulating the amount of sodium in the body. Sodium regulation plays a role in blood pressure control and fluid balance. Certain hormones called mineralocorticoids attach (bind) to and turn on (activate) the mineralocorticoid receptor. Aldosterone is one mineralocorticoid that activates the mineralocorticoid receptor. The activated mineralocorticoid receptor acts as a transcription factor, which is a protein that binds to specific regions of DNA and helps control the activity (transcription) of particular genes.

The mineralocorticoid receptor regulates specialized proteins in the cell membrane that control the transport of sodium or potassium into cells. In response to signals that sodium levels in the body are low, the mineralocorticoid receptor increases the number and activity of these proteins at the cell membrane, especially in certain kidney cells. One of these proteins transports sodium into the cell, while another protein simultaneously transports sodium out of the cell and potassium into the cell. These proteins help keep sodium in the body through a process called reabsorption and remove potassium from the body through a process called secretion.

2. Health Conditions Related to Genetic Changes

2.1. Pseudohypoaldosteronism type 1

More than 50 mutations in the NR3C2 gene have been identified in people with pseudohypoaldosteronism type 1 (PHA1), a condition that typically begins in infancy and is characterized by low levels of sodium (hyponatremia) and high levels of potassium (hyperkalemia) in the blood. In particular, NR3C2 gene mutations are involved in autosomal dominant PHA1, a relatively mild form of the condition that can improve in childhood.

Mutations in the NR3C2 gene lead to a nonfunctional or abnormally functioning mineralocorticoid receptor protein that cannot properly regulate the specialized proteins that transport sodium and potassium. As a result, sodium reabsorption and potassium secretion are both decreased, causing hyponatremia and hyperkalemia.

2.2. Other disorders

One particular mutation in the NR3C2 gene can cause early-onset hypertension with severe exacerbation in pregnancy. People with this condition develop high blood pressure (hypertension) at an early age. The condition can affect males or females, and hypertension worsens in pregnant females.

The mutation involved in this condition changes one protein building block (amino acid) in the mineralocorticoid receptor protein. The amino acid serine is replaced with the amino acid leucine at position 810 in the protein (written as Ser810Leu or S810L). This mutation changes the shape of the receptor, which allows the receptor to be abnormally activated by non-mineralocorticoid hormones such as progesterone and cortisol. The increased mineralocorticoid receptor activity causes excessive sodium reabsorption, which leads to hypertension. Progesterone levels are elevated during pregnancy, which is why the condition worsens in pregnant females.

3. Other Names for This Gene

aldosterone receptor
FLJ41052
MCR
MCR_HUMAN
MGC133092
mineralocorticoid receptor
mineralocorticoid receptor 1
mineralocorticoid receptor delta
MLR
MR
NR3C2VIT
nuclear receptor subfamily 3, group C, member 2

References

Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, FirestoneGL, Verrey F, Pearce D. Epithelial sodium channel regulated byaldosterone-induced protein sgk. Proc Natl Acad Sci U S A. 1999 Mar2;96(5):2514-9.
Geller DS, Farhi A, Pinkerton N, Fradley M, Moritz M, Spitzer A, Meinke G,Tsai FT, Sigler PB, Lifton RP. Activating mineralocorticoid receptor mutation in hypertension exacerbated by pregnancy. Science. 2000 Jul 7;289(5476):119-23.
Kolla V, Litwack G. Transcriptional regulation of the human Na/K ATPase viathe human mineralocorticoid receptor. Mol Cell Biochem. 2000 Jan;204(1-2):35-40.
Martinez F, Mansego ML, Escudero JC, Redon J, Chaves FJ. Association of amineralocorticoid receptor gene polymorphism with hypertension in a Spanishpopulation. Am J Hypertens. 2009 Jun;22(6):649-55. doi: 10.1038/ajh.2009.39.
Pujo L, Fagart J, Gary F, Papadimitriou DT, Claës A, Jeunemaître X, ZennaroMC. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007 Jan;28(1):33-40.
Rafestin-Oblin ME, Souque A, Bocchi B, Pinon G, Fagart J, Vandewalle A. Thesevere form of hypertension caused by the activating S810L mutation in themineralocorticoid receptor is cortisone related. Endocrinology. 2003Feb;144(2):528-33.
Riepe FG, Finkeldei J, de Sanctis L, Einaudi S, Testa A, Karges B, Peter M,Viemann M, Grötzinger J, Sippell WG, Fejes-Toth G, Krone N. Elucidating theunderlying molecular pathogenesis of NR3C2 mutants causing autosomal dominantpseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2006 Nov;91(11):4552-61.
van Leeuwen N, Caprio M, Blaya C, Fumeron F, Sartorato P, Ronconi V,Giacchetti G, Mantero F, Fernandes-Rosa FL, Simian C, Peyrard S, Zitman FG,Penninx BW, de Kloet ER, Azizi M, Jeunemaitre X, Derijk RH, Zennaro MC. Thefunctional c.-2G>C variant of the mineralocorticoid receptor modulates bloodpressure, renin, and aldosterone levels. Hypertension. 2010 Nov;56(5):995-1002.doi: 10.1161/HYPERTENSIONAHA.110.155630.
Viengchareun S, Le Menuet D, Martinerie L, Munier M, Pascual-Le Tallec L,Lombès M. The mineralocorticoid receptor: insights into its molecular and(patho)physiological biology. Nucl Recept Signal. 2007 Nov 30;5:e012. doi:10.1621/nrs.05012. Review.

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Subjects: Genetics & Heredity

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Lily Guo

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Entry Collection: MedlinePlus

Update Date: 24 Dec 2020

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