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Genetics Home Reference: your guide to understanding genetic conditions
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AVPR2

Reviewed April 2010

What is the official name of the AVPR2 gene?

The official name of this gene is “arginine vasopressin receptor 2.”

AVPR2 is the gene's official symbol. The AVPR2 gene is also known by other names, listed below.

What is the normal function of the AVPR2 gene?

The AVPR2 gene provides instructions for making a protein known as the vasopressin V2 receptor. This receptor works together with a hormone called vasopressin or antidiuretic hormone (ADH) in the kidneys. The vasopressin V2 receptor is found in structures called collecting ducts, which are a series of small tubes that reabsorb water from the kidneys into the bloodstream.

The interaction between ADH and the vasopressin V2 receptor triggers chemical reactions that control the body's water balance. When a person's fluid intake is low or when a lot of fluid is lost (for example, through sweating), the body produces more ADH. This hormone attaches (binds) to the vasopressin V2 receptor and directs the kidneys to concentrate urine by reabsorbing some of the water back into the bloodstream. When fluid intake is adequate, less ADH is available to interact with the vasopressin V2 receptor. At these times, less water is reabsorbed into the bloodstream and the urine is more dilute.

How are changes in the AVPR2 gene related to health conditions?

nephrogenic diabetes insipidus - caused by mutations in the AVPR2 gene

More than 200 mutations in the AVPR2 gene have been identified in people with nephrogenic diabetes insipidus. Most of these mutations cause the vasopressin V2 receptor protein to be misfolded into an incorrect 3-dimensional shape. The misfolded protein is trapped within the cell, where it is unable to reach the cell surface to interact with ADH. Less common mutations in the AVPR2 gene prevent the production of any vasopressin V2 receptor protein or lead to a version of the protein that reaches the cell surface but cannot partner with ADH.

Without functional vasopressin V2 receptors, the kidneys are unable to respond to signals from ADH. As a result, collecting ducts do not reabsorb water as they should, and the body makes excessive amounts of urine. These problems with water balance are characteristic of nephrogenic diabetes insipidus.

other disorders - caused by mutations in the AVPR2 gene

At least two mutations in the AVPR2 gene have been found to cause another kidney disorder known as nephrogenic syndrome of inappropriate antidiuresis (NSIAD). This condition is characterized by low levels of salt in the blood (hyponatremia), which can lead to brain swelling and other serious complications. NSIAD also causes the blood to be abnormally dilute (serum hypo-osmolality).

The two AVPR2 gene mutations associated with NSIAD each change a single protein building block (amino acid) at position 137 in the vasopressin V2 receptor protein. One of these mutations replaces the amino acid arginine with the amino acid cysteine (written as Arg137Cys or R137C); the other mutation replaces arginine with the amino acid leucine (written as Arg137Leu or R137L). These mutations lead to a receptor protein that is constantly turned on (constitutively activated), even in the absence of ADH. As a result, large amounts of water are reabsorbed into the bloodstream regardless of fluid intake, and the urine is highly concentrated. These abnormalities disrupt the body's water balance, causing hyponatremia and serum hypo-osmolality.

Where is the AVPR2 gene located?

Cytogenetic Location: Xq28

Molecular Location on the X chromosome: base pairs 153,902,530 to 153,907,165

The AVPR2 gene is located on the long (q) arm of the X chromosome at position 28.

The AVPR2 gene is located on the long (q) arm of the X chromosome at position 28.

More precisely, the AVPR2 gene is located from base pair 153,902,530 to base pair 153,907,165 on the X chromosome.

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 AVPR2?

You and your healthcare professional may find the following resources about AVPR2 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 AVPR2 gene or gene products?

  • ADHR
  • antidiuretic hormone receptor
  • AVPR V2
  • DI1
  • DIR
  • DIR3
  • MGC126533
  • MGC138386
  • NDI
  • renal-type arginine vasopressin receptor
  • V2R
  • V2R_HUMAN
  • vasopressin V2 receptor

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 AVPR2?

amino acid ; arginine ; cell ; cysteine ; diabetes ; gene ; hormone ; hyponatremia ; kidney ; leucine ; mutation ; protein ; receptor ; renal ; syndrome

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

References

  • Arthus MF, Lonergan M, Crumley MJ, Naumova AK, Morin D, De Marco LA, Kaplan BS, Robertson GL, Sasaki S, Morgan K, Bichet DG, Fujiwara TM. Report of 33 novel AVPR2 mutations and analysis of 117 families with X-linked nephrogenic diabetes insipidus. J Am Soc Nephrol. 2000 Jun;11(6):1044-54. (http://www.ncbi.nlm.nih.gov/pubmed/10820168?dopt=Abstract)
  • Bichet DG. Vasopressin receptor mutations in nephrogenic diabetes insipidus. Semin Nephrol. 2008 May;28(3):245-51. doi: 10.1016/j.semnephrol.2008.03.005. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18519085?dopt=Abstract)
  • Feldman BJ, Rosenthal SM, Vargas GA, Fenwick RG, Huang EA, Matsuda-Abedini M, Lustig RH, Mathias RS, Portale AA, Miller WL, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis. N Engl J Med. 2005 May 5;352(18):1884-90. (http://www.ncbi.nlm.nih.gov/pubmed/15872203?dopt=Abstract)
  • Knoers NV, Deen PM. Molecular and cellular defects in nephrogenic diabetes insipidus. Pediatr Nephrol. 2001 Dec;16(12):1146-52. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11793119?dopt=Abstract)
  • Knoers NV. Hyperactive vasopressin receptors and disturbed water homeostasis. N Engl J Med. 2005 May 5;352(18):1847-50. (http://www.ncbi.nlm.nih.gov/pubmed/15872199?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/554)
  • Robben JH, Knoers NV, Deen PM. Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus. Am J Physiol Renal Physiol. 2006 Aug;291(2):F257-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16825342?dopt=Abstract)
  • Rosenthal SM, Feldman BJ, Vargas GA, Gitelman SE. Nephrogenic syndrome of inappropriate antidiuresis (NSIAD): a paradigm for activating mutations causing endocrine dysfunction. Pediatr Endocrinol Rev. 2006 Dec;4 Suppl 1:66-70. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17261972?dopt=Abstract)
  • Spanakis E, Milord E, Gragnoli C. AVPR2 variants and mutations in nephrogenic diabetes insipidus: review and missense mutation significance. J Cell Physiol. 2008 Dec;217(3):605-17. doi: 10.1002/jcp.21552. Review. (http://www.ncbi.nlm.nih.gov/pubmed/18726898?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: April 2010
Published: July 7, 2014