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Genetics Home Reference: your guide to understanding genetic conditions
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NR3C2

Reviewed December 2011

What is the official name of the NR3C2 gene?

The official name of this gene is “nuclear receptor subfamily 3, group C, member 2.”

NR3C2 is the gene's official symbol. The NR3C2 gene is also known by other names, listed below.

What is the normal function of the NR3C2 gene?

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.

Does the NR3C2 gene share characteristics with other genes?

The NR3C2 gene belongs to a family of genes called NR (nuclear hormone receptors).

A gene family is a group of genes that share important characteristics. Classifying individual genes into families helps researchers describe how genes are related to each other. For more information, see What are gene families? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genefamilies) in the Handbook.

How are changes in the NR3C2 gene related to health conditions?

pseudohypoaldosteronism type 1 - caused by mutations in the NR3C2 gene

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.

other disorders - associated with the NR3C2 gene

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.

Where is the NR3C2 gene located?

Cytogenetic Location: 4q31.1

Molecular Location on chromosome 4: base pairs 148,078,763 to 148,444,697

The NR3C2 gene is located on the long (q) arm of chromosome 4 at position 31.1.

The NR3C2 gene is located on the long (q) arm of chromosome 4 at position 31.1.

More precisely, the NR3C2 gene is located from base pair 148,078,763 to base pair 148,444,697 on chromosome 4.

See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.

Where can I find additional information about NR3C2?

You and your healthcare professional may find the following resources about NR3C2 helpful.

You may also be interested in these resources, which are designed for genetics professionals and researchers.

What other names do people use for the NR3C2 gene or gene products?

  • aldosterone receptor
  • FLJ41052
  • MCR
  • MCR_HUMAN
  • MGC133092
  • mineralocorticoid receptor
  • mineralocorticoid receptor 1
  • mineralocorticoid receptor delta
  • MLR
  • MR
  • NR3C2VIT

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding NR3C2?

aldosterone ; amino acid ; autosomal ; autosomal dominant ; cell ; cell membrane ; DNA ; gene ; hyperkalemia ; hypertension ; hyponatremia ; kidney ; leucine ; mutation ; potassium ; progesterone ; protein ; receptor ; secretion ; serine ; sodium ; transcription ; transcription factor

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Chen SY, Bhargava A, Mastroberardino L, Meijer OC, Wang J, Buse P, Firestone GL, Verrey F, Pearce D. Epithelial sodium channel regulated by aldosterone-induced protein sgk. Proc Natl Acad Sci U S A. 1999 Mar 2;96(5):2514-9. (http://www.ncbi.nlm.nih.gov/pubmed/10051674?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/10884226?dopt=Abstract)
  • Kolla V, Litwack G. Transcriptional regulation of the human Na/K ATPase via the human mineralocorticoid receptor. Mol Cell Biochem. 2000 Jan;204(1-2):35-40. (http://www.ncbi.nlm.nih.gov/pubmed/10718622?dopt=Abstract)
  • Martinez F, Mansego ML, Escudero JC, Redon J, Chaves FJ. Association of a mineralocorticoid receptor gene polymorphism with hypertension in a Spanish population. Am J Hypertens. 2009 Jun;22(6):649-55. doi: 10.1038/ajh.2009.39. Epub 2009 Mar 26. (http://www.ncbi.nlm.nih.gov/pubmed/19325532?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/4306)
  • OMIM: NUCLEAR RECEPTOR SUBFAMILY 3, GROUP C, MEMBER 2 (http://omim.org/entry/600983)
  • Pujo L, Fagart J, Gary F, Papadimitriou DT, Claës A, Jeunemaître X, Zennaro MC. Mineralocorticoid receptor mutations are the principal cause of renal type 1 pseudohypoaldosteronism. Hum Mutat. 2007 Jan;28(1):33-40. (http://www.ncbi.nlm.nih.gov/pubmed/16972228?dopt=Abstract)
  • Rafestin-Oblin ME, Souque A, Bocchi B, Pinon G, Fagart J, Vandewalle A. The severe form of hypertension caused by the activating S810L mutation in the mineralocorticoid receptor is cortisone related. Endocrinology. 2003 Feb;144(2):528-33. (http://www.ncbi.nlm.nih.gov/pubmed/12538613?dopt=Abstract)
  • 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 the underlying molecular pathogenesis of NR3C2 mutants causing autosomal dominant pseudohypoaldosteronism type 1. J Clin Endocrinol Metab. 2006 Nov;91(11):4552-61. Epub 2006 Sep 5. (http://www.ncbi.nlm.nih.gov/pubmed/16954160?dopt=Abstract)
  • 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. The functional c.-2G>C variant of the mineralocorticoid receptor modulates blood pressure, renin, and aldosterone levels. Hypertension. 2010 Nov;56(5):995-1002. doi: 10.1161/HYPERTENSIONAHA.110.155630. Epub 2010 Sep 20. (http://www.ncbi.nlm.nih.gov/pubmed/20855654?dopt=Abstract)
  • 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. (http://www.ncbi.nlm.nih.gov/pubmed/18174920?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: December 2011
Published: December 16, 2014