Gene: PRKAG2

Alternate names for this Gene: AAKG|AAKG2|CMH6|H91620p|WPWS

Gene Summary: AMP-activated protein kinase (AMPK) is a heterotrimeric protein composed of a catalytic alpha subunit, a noncatalytic beta subunit, and a noncatalytic regulatory gamma subunit. Various forms of each of these subunits exist, encoded by different genes. AMPK is an important energy-sensing enzyme that monitors cellular energy status and functions by inactivating key enzymes involved in regulating de novo biosynthesis of fatty acid and cholesterol. This gene is a member of the AMPK gamma subunit family. Mutations in this gene have been associated with Wolff-Parkinson-White syndrome, familial hypertrophic cardiomyopathy, and glycogen storage disease of the heart. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Gene is located in Chromosome: 7

Location in Chromosome : 7q36.1

Description of this Gene: protein kinase AMP-activated non-catalytic subunit gamma 2

Type of Gene: protein-coding

rs10265221 in PRKAG2 gene and Amino acids measurement PMID 27005778 2016 Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.

rs10480300 in PRKAG2 gene and Arthritis, Gouty PMID 23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

rs10224210 in PRKAG2 gene and Blood urea nitrogen measurement PMID 28270201 2017 Exploration of haplotype research consortium imputation for genome-wide association studies in 20,032 Generation Scotland participants.

PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.

rs121908987 in PRKAG2 gene and CARDIOMYOPATHY, FAMILIAL HYPERTROPHIC, 6 (disorder) PMID 11407343 2001 Identification of a gene responsible for familial Wolff-Parkinson-White syndrome.

PMID 11371514 2001 Mutations in the gamma(2) subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis.

PMID 14722619 2004 CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.

PMID 27854360 2017 Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics.

PMID 11827995 2002 Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy.

PMID 28917552 2018 CRISPR correction of the PRKAG2 gene mutation in the patient's induced pluripotent stem cell-derived cardiomyocytes eliminates electrophysiological and structural abnormalities.

PMID 21267010 2011 Clinical utility gene card for: hypertrophic cardiomyopathy (type 1-14).

PMID 15611370 2005 Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome.

PMID 25356965 2015 ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.

PMID 23788249 2013 ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.

PMID 25173338 2014 2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).

rs267606976 in PRKAG2 gene and Cardiomyopathies PMID 15673802 2005 Glycogen storage diseases presenting as hypertrophic cardiomyopathy.

PMID 23992123 2014 Overexpression of G100S mutation in PRKAG2 causes Wolff-Parkinson-White syndrome in zebrafish.

rs10224210 in PRKAG2 gene and Cardiovascular Diseases PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs7805747 in PRKAG2 gene and Chronic Kidney Diseases PMID 20383146 2010 New loci associated with kidney function and chronic kidney disease.

PMID 22479191 2012 Genome-wide association and functional follow-up reveals new loci for kidney function.

rs10224002 in PRKAG2 gene and Corpuscular Hemoglobin Concentration Mean PMID 23222517 2012 Seventy-five genetic loci influencing the human red blood cell.

rs10254101 in PRKAG2 gene and Creatinine measurement, serum (procedure) PMID 28452372 2017 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

PMID 31015462 2019 Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis.

PMID 26831199 2016 Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

rs17173197 in PRKAG2 gene and Dermatitis, Atopic PMID 21666691 2011 Genome-wide association study identifies two new susceptibility loci for atopic dermatitis in the Chinese Han population.

rs10224002 in PRKAG2 gene and Diabetes PMID 29703844 2018 A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.

PMID 31451708 2019 Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.

rs10224002 in PRKAG2 gene and Diabetes Mellitus PMID 29703844 2018 A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.

PMID 31451708 2019 Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.

rs10224002 in PRKAG2 gene and Diabetes Mellitus, Non-Insulin-Dependent PMID 29703844 2018 A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.

rs10224002 in PRKAG2 gene and Diastolic blood pressure PMID 27841878 2017 Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

rs10224002 in PRKAG2 gene and Glomerular Filtration Rate PMID 29703844 2018 A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes.

PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.

PMID 31451708 2019 Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.

PMID 28452372 2017 1000 Genomes-based meta-analysis identifies 10 novel loci for kidney function.

PMID 30604766 2019 Trans-ethnic kidney function association study reveals putative causal genes and effects on kidney-specific disease aetiologies.

PMID 27588450 2016 Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity.

PMID 31015462 2019 Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis.

PMID 26831199 2016 Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

rs121908987 in PRKAG2 gene and Glycogen Storage Disease of Heart, Lethal Congenital PMID 25997934 2015 Using exome sequencing to identify the cause of myocardial hypertrophy in a Chinese family.

PMID 23992123 2014 Overexpression of G100S mutation in PRKAG2 causes Wolff-Parkinson-White syndrome in zebrafish.

PMID 20031621 2009 Distinct early signaling events resulting from the expression of the PRKAG2 R302Q mutant of AMPK contribute to increased myocardial glycogen.

PMID 14722619 2004 CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.

PMID 15611370 2005 Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome.

PMID 16836667 2006 Familial pseudo-Wolff-Parkinson-White syndrome.

PMID 27621313 2016 Physiological Expression of AMPKγ2RG Mutation Causes Wolff-Parkinson-White Syndrome and Induces Kidney Injury in Mice.

PMID 15877279 2005 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.

PMID 25611685 2015 Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

PMID 11748095 2001 Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy.

PMID 26085771 2015 PRKAG2 mutation: An easily missed cardiac specific non-lysosomal glycogenosis.

PMID 27573176 2016 Genome editing with CRISPR/Cas9 in postnatal mice corrects PRKAG2 cardiac syndrome.

PMID 18403758 2008 Shared genetic causes of cardiac hypertrophy in children and adults.

rs10480300 in PRKAG2 gene and Gout PMID 23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

rs10224002 in PRKAG2 gene and Hematocrit procedure PMID 19862010 2009 Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

PMID 28017375 2017 Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs10224002 in PRKAG2 gene and Hemoglobin measurement PMID 19862010 2009 Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

PMID 28017375 2017 Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis.

PMID 23222517 2012 Seventy-five genetic loci influencing the human red blood cell.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs10224002 in PRKAG2 gene and Hemoglobin, CTCAE PMID 19862010 2009 Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

rs1881626 in PRKAG2 gene and High density lipoprotein measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs121908987 in PRKAG2 gene and Hypertrophic Cardiomyopathy PMID 15611370 2005 Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome.

PMID 17483151 2007 A familial form of conduction defect related to a mutation in the PRKAG2 gene.

PMID 17711718 2007 [Same genotype and different phenotypes in a family with PRKAG2 gene mutation].

PMID 14722619 2004 CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.

PMID 11407343 2001 Identification of a gene responsible for familial Wolff-Parkinson-White syndrome.

PMID 20031621 2009 Distinct early signaling events resulting from the expression of the PRKAG2 R302Q mutant of AMPK contribute to increased myocardial glycogen.

PMID 11827995 2002 Although the cardiac pathology caused by PRKAG2 mutations Arg302Gln, Thr400Asn, and Asn488Ile include myocyte enlargement and minimal interstitial fibrosis, these mutations were not associated with myocyte and myofibrillar disarray, the pathognomonic features of hypertrophic cardiomyopathy caused by sarcomere protein mutations.

PMID 16836667 2006 Familial pseudo-Wolff-Parkinson-White syndrome.

PMID 23778007 2013 Identification and functional analysis of a novel PRKAG2 mutation responsible for Chinese PRKAG2 cardiac syndrome reveal an important role of non-CBS domains in regulating the AMPK pathway.

PMID 19808419 2008 Nodoventricular accessory pathways in PRKAG2-dependent familial preexcitation syndrome reveal a disorder in cardiac development.

PMID 23829931 2013 Chronic AMPK activity dysregulation produces myocardial insulin resistance in the human Arg302Gln-PRKAG2 glycogen storage disease mouse model.

PMID 27532257 2017 Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

PMID 25611685 2015 Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

PMID 14519435 2003 Mutation analysis of AMP-activated protein kinase subunits in inherited cardiomyopathies: implications for kinase function and disease pathogenesis.

PMID 15877279 2005 Thus, recurrent heterozygous R531Q missense mutations in PRKAG2 give rise to a massive nonlysosomal cardiac glycogenosis of fetal symptomatic onset and rapidly fatal course, constituting a genotypically and clinically distinct variant of hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome.

PMID 16716659 2006 Ventricular pre-excitation and cardiac hypertrophy mimicking hypertrophic cardiomyopathy in a Turkish family with a novel PRKAG2 mutation.

PMID 19787389 2009 Severe hypertrophic cardiomyopathy in an infant with a novel PRKAG2 gene mutation: potential differences between infantile and adult onset presentation.

PMID 20005292 2010 Activation of cardiac hypertrophic signaling pathways in a transgenic mouse with the human PRKAG2 Thr400Asn mutation.

PMID 16487706 2006 A new mutation in PRKAG2 gene causing hypertrophic cardiomyopathy with conduction system disease and muscular glycogenosis.

PMID 17597581 2007 A PRKAG2 mutation causes biphasic changes in myocardial AMPK activity and does not protect against ischemia.

PMID 11827995 2002 Although the cardiac pathology caused by PRKAG2 mutations Arg302Gln, Thr400Asn, and Asn488Ile include myocyte enlargement and minimal interstitial fibrosis, these mutations were not associated with myocyte and myofibrillar disarray, the pathognomonic features of hypertrophic cardiomyopathy caused by sarcomere protein mutations.

PMID 25092788 2014 Transgenic knockdown of cardiac sodium/glucose cotransporter 1 (SGLT1) attenuates PRKAG2 cardiomyopathy, whereas transgenic overexpression of cardiac SGLT1 causes pathologic hypertrophy and dysfunction in mice.

PMID 26729852 2016 Clinical Spectrum of PRKAG2 Syndrome.

PMID 20600102 2010 SGLT1, a novel cardiac glucose transporter, mediates increased glucose uptake in PRKAG2 cardiomyopathy.

rs73728279 in PRKAG2 gene and Kidney Failure, Chronic PMID 31152163 2019 A catalog of genetic loci associated with kidney function from analyses of a million individuals.

PMID 20383146 2010 New loci associated with kidney function and chronic kidney disease.

PMID 26831199 2016 Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

rs12113155 in PRKAG2 gene and Low density lipoprotein cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs4726066 in PRKAG2 gene and Proliferative diabetic retinopathy PMID 30487263 2019 Multiethnic Genome-Wide Association Study of Diabetic Retinopathy Using Liability Threshold Modeling of Duration of Diabetes and Glycemic Control.

rs10265221 in PRKAG2 gene and Protein measurement PMID 27005778 2016 Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.

rs10263707 in PRKAG2 gene and RDW - Red blood cell distribution width result PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs10224210 in PRKAG2 gene and Red Blood Cell Count measurement PMID 19862010 2009 Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium.

PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs10263707 in PRKAG2 gene and Red cell distribution width determination PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1881626 in PRKAG2 gene and Serum HDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs12113155 in PRKAG2 gene and Serum LDL cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs12113155 in PRKAG2 gene and Serum total cholesterol measurement PMID 23063622 2012 Large-scale gene-centric meta-analysis across 32 studies identifies multiple lipid loci.

rs10480299 in PRKAG2 gene and Serum urea measurement PMID 31015462 2019 Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis.

rs10224002 in PRKAG2 gene and Systolic Pressure PMID 27618447 2016 Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

PMID 27841878 2017 Genome-wide association analyses using electronic health records identify new loci influencing blood pressure variation.

PMID 30578418 2019 Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs4128399 in PRKAG2 gene and Tonometry PMID 29785010 2018 Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.

rs10480300 in PRKAG2 gene and Uric acid measurement (procedure) PMID 31578528 2019 Target genes, variants, tissues and transcriptional pathways influencing human serum urate levels.

PMID 23263486 2013 Genome-wide association analyses identify 18 new loci associated with serum urate concentrations.

rs121908987 in PRKAG2 gene and Wolff-Parkinson-White Syndrome PMID 11407343 2001 Identification of a gene responsible for familial Wolff-Parkinson-White syndrome.

PMID 11748095 2001 Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy.

PMID 14722619 2004 CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations.

rs1345278 in PRKAG2 gene and mathematical ability PMID 30038396 2018 Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.