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Genetics Home Reference: your guide to understanding genetic conditions
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PRKAG2

Reviewed February 2007

What is the official name of the PRKAG2 gene?

The official name of this gene is “protein kinase, AMP-activated, gamma 2 non-catalytic subunit.”

PRKAG2 is the gene's official symbol. The PRKAG2 gene is also known by other names, listed below.

What is the normal function of the PRKAG2 gene?

The PRKAG2 gene provides instructions for making one part (the gamma-2 subunit) of a larger enzyme called AMP-activated protein kinase (AMPK). This enzyme helps sense and respond to energy demands within cells. It is active in many different tissues, including heart (cardiac) muscle and muscles used for movement (skeletal muscles). AMP-activated protein kinase is likely involved in the development of the heart before birth, although its role in this process is unknown.

AMP-activated protein kinase regulates chemical pathways involving the cell's main energy source, a molecule called adenosine triphosphate (ATP). The breakdown of ATP releases energy to drive many types of chemical reactions. AMP-activated protein kinase is activated during times of cellular stress (such as low oxygen levels or muscle exercise), when ATP is broken down rapidly to produce energy. If ATP levels become too low, the enzyme restores the balance of energy by limiting chemical reactions that require ATP and stimulating pathways that generate ATP.

Studies suggest that AMP-activated protein kinase may play a role in controlling the activity of other genes, although many of these genes have not been identified. The enzyme may also regulate the activity of certain ion channels in the heart. These channels, which transport positively charged atoms (ions) into and out of heart muscle cells, play critical roles in maintaining the heart's normal rhythm.

How are changes in the PRKAG2 gene related to health conditions?

Wolff-Parkinson-White syndrome - caused by mutations in the PRKAG2 gene

At least seven mutations that cause Wolff-Parkinson-White syndrome have been identified in the PRKAG2 gene. Some people with these mutations also have features of hypertrophic cardiomyopathy, a form of heart disease that enlarges and weakens the heart (cardiac) muscle. Researchers are uncertain how PRKAG2 mutations lead to the development of these heart conditions. Research suggests that these mutations alter the activity of AMP-activated protein kinase in the heart, disrupting the enzyme's ability to respond to changes in cellular energy demands. It is unclear, however, whether the genetic changes overactivate the enzyme or reduce its activity.

Studies indicate that changes in AMP-activated protein kinase activity allow a complex sugar called glycogen to build up abnormally within cardiac muscle cells. The accumulation of this substance enlarges these cells, which may lead to hypertrophic cardiomyopathy. Researchers continue to investigate whether an abnormal buildup of glycogen in the heart is also responsible for the problems with electrical signaling that are characteristic of Wolff-Parkinson-White syndrome.

Other studies have found that altered AMP-activated protein kinase activity is related to changes in the regulation of certain ion channels in the heart. These changes may help explain the increased risk of abnormal heart rhythms (arrhythmias) in people with Wolff-Parkinson-White syndrome.

other disorders - caused by mutations in the PRKAG2 gene

Several mutations in the PRKAG2 gene have been found in people with other heart conditions. For example, a specific mutation in this gene is responsible for a very severe form of heart disease called lethal congenital glycogen storage disease of the heart. People with this mutation are born with extremely enlarged hearts (cardiomegaly) and abnormal electrical signaling within the heart. These abnormalities lead to respiratory distress and heart failure early in life. The mutation responsible for this condition changes a single protein building block (amino acid) in the gamma-2 subunit of AMP-activated protein kinase. Specifically, this mutation replaces the amino acid arginine with the amino acid glutamine at position 531 (written as Arg531Gln or R531Q). Studies suggest that this severe disorder may be related to the abnormal buildup of glycogen within cardiac muscle cells.

Other mutations in the PRKAG2 gene have been associated with disorders affecting both cardiac and skeletal muscle. These mutations change single amino acids in the gamma-2 subunit of AMP-activated protein kinase. Individuals with these genetic changes typically experience muscle pain and stiffness, particularly following exercise, in addition to hypertrophic cardiomyopathy and abnormal electrical signaling within the heart. It is not known why the effects of some PRKAG2 mutations appear to be confined to the heart, while other mutations cause signs and symptoms affecting both cardiac and skeletal muscles.

Where is the PRKAG2 gene located?

Cytogenetic Location: 7q36.1

Molecular Location on chromosome 7: base pairs 151,556,113 to 151,877,230

The PRKAG2 gene is located on the long (q) arm of chromosome 7 at position 36.1.

The PRKAG2 gene is located on the long (q) arm of chromosome 7 at position 36.1.

More precisely, the PRKAG2 gene is located from base pair 151,556,113 to base pair 151,877,230 on chromosome 7.

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 PRKAG2?

You and your healthcare professional may find the following resources about PRKAG2 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 PRKAG2 gene or gene products?

  • AAKG
  • AAKG2
  • AAKG2_HUMAN
  • AMP-activated protein kinase gamma2 subunit
  • AMPK gamma2
  • CMH6
  • H91620p
  • WPWS

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 PRKAG2?

acids ; adenosine triphosphate ; amino acid ; arginine ; ATP ; breakdown ; cardiac ; cardiomyopathy ; catalytic ; cell ; congenital ; enzyme ; familial ; gene ; glutamine ; glycogen ; heart failure ; hypertrophic ; ions ; kinase ; molecule ; muscle cells ; mutation ; oxygen ; protein ; respiratory ; skeletal muscle ; stress ; subunit ; 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

  • Ahmad F, Arad M, Musi N, He H, Wolf C, Branco D, Perez-Atayde AR, Stapleton D, Bali D, Xing Y, Tian R, Goodyear LJ, Berul CI, Ingwall JS, Seidman CE, Seidman JG. Increased alpha2 subunit-associated AMPK activity and PRKAG2 cardiomyopathy. Circulation. 2005 Nov 15;112(20):3140-8. Epub 2005 Nov 7. (http://www.ncbi.nlm.nih.gov/pubmed/16275868?dopt=Abstract)
  • Burwinkel B, Scott JW, Bührer C, van Landeghem FK, Cox GF, Wilson CJ, Grahame Hardie D, Kilimann MW. Fatal congenital heart glycogenosis caused by a recurrent activating R531Q mutation in the gamma 2-subunit of AMP-activated protein kinase (PRKAG2), not by phosphorylase kinase deficiency. Am J Hum Genet. 2005 Jun;76(6):1034-49. Epub 2005 May 2. (http://www.ncbi.nlm.nih.gov/pubmed/15877279?dopt=Abstract)
  • Daniel T, Carling D. Functional analysis of mutations in the gamma 2 subunit of AMP-activated protein kinase associated with cardiac hypertrophy and Wolff-Parkinson-White syndrome. J Biol Chem. 2002 Dec 27;277(52):51017-24. Epub 2002 Oct 22. (http://www.ncbi.nlm.nih.gov/pubmed/12397075?dopt=Abstract)
  • Gollob MH, Green MS, Tang AS, Gollob T, Karibe A, Ali Hassan AS, Ahmad F, Lozado R, Shah G, Fananapazir L, Bachinski LL, Roberts R. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. N Engl J Med. 2001 Jun 14;344(24):1823-31. Erratum in: N Engl J Med 2001 Aug 16;345(7):552. Hassan AS [corrected to Ali Hassan AS]. N Engl J Med 2002 Jan 24;346(4):300. (http://www.ncbi.nlm.nih.gov/pubmed/11407343?dopt=Abstract)
  • Gollob MH, Green MS, Tang AS, Roberts R. PRKAG2 cardiac syndrome: familial ventricular preexcitation, conduction system disease, and cardiac hypertrophy. Curr Opin Cardiol. 2002 May;17(3):229-34. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12015471?dopt=Abstract)
  • Gollob MH, Seger JJ, Gollob TN, Tapscott T, Gonzales O, Bachinski L, Roberts R. Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation. 2001 Dec 18;104(25):3030-3. (http://www.ncbi.nlm.nih.gov/pubmed/11748095?dopt=Abstract)
  • Hardie DG, Sakamoto K. AMPK: a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda). 2006 Feb;21:48-60. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16443822?dopt=Abstract)
  • Laforêt P, Richard P, Said MA, Romero NB, Lacene E, Leroy JP, Baussan C, Hogrel JY, Lavergne T, Wahbi K, Hainque B, Duboc D. A new mutation in PRKAG2 gene causing hypertrophic cardiomyopathy with conduction system disease and muscular glycogenosis. Neuromuscul Disord. 2006 Mar;16(3):178-82. Epub 2006 Feb 17. (http://www.ncbi.nlm.nih.gov/pubmed/16487706?dopt=Abstract)
  • Murphy RT, Mogensen J, McGarry K, Bahl A, Evans A, Osman E, Syrris P, Gorman G, Farrell M, Holton JL, Hanna MG, Hughes S, Elliott PM, Macrae CA, McKenna WJ. Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome: natural history. J Am Coll Cardiol. 2005 Mar 15;45(6):922-30. (http://www.ncbi.nlm.nih.gov/pubmed/15766830?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/51422)
  • Oliveira SM, Ehtisham J, Redwood CS, Ostman-Smith I, Blair EM, Watkins H. Mutation analysis of AMP-activated protein kinase subunits in inherited cardiomyopathies: implications for kinase function and disease pathogenesis. J Mol Cell Cardiol. 2003 Oct;35(10):1251-5. (http://www.ncbi.nlm.nih.gov/pubmed/14519435?dopt=Abstract)
  • Sternick EB, Oliva A, Magalhães LP, Gerken LM, Hong K, Santana O, Brugada P, Brugada J, Brugada R. Familial pseudo-Wolff-Parkinson-White syndrome. J Cardiovasc Electrophysiol. 2006 Jul;17(7):724-32. (http://www.ncbi.nlm.nih.gov/pubmed/16836667?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: February 2007
Published: September 15, 2014