Gene: KCNJ11

Alternate names for this Gene: BIR|HHF2|IKATP|KIR6.2|MODY13|PHHI|PNDM2|TNDM3

Gene Summary: Potassium channels are present in most mammalian cells, where they participate in a wide range of physiologic responses. The protein encoded by this gene is an integral membrane protein and inward-rectifier type potassium channel. The encoded protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor SUR. Mutations in this gene are a cause of familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM), transient neonatal diabetes mellitus type 3 (TNDM3), and permanent neonatal diabetes mellitus (PNDM). Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene.

Gene is located in Chromosome: 11

Location in Chromosome : 11p15.1

Description of this Gene: potassium inwardly rectifying channel subfamily J member 11

Type of Gene: protein-coding

rs5215 in KCNJ11 gene and Body mass index PMID 28892062 2017 Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.

PMID 30239722 2019 Meta-analysis of genome-wide association studies for body fat distribution in 694 649 individuals of European ancestry.

PMID 29273807 2018 Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

rs5215 in KCNJ11 gene and Coronary heart disease PMID 21347282 2011 Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project.

rs1371185696 in KCNJ11 gene and DIABETES MELLITUS, PERMANENT NEONATAL PMID 11395395 2001 Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11.

PMID 21422196 2011 Characterization of ABCC8 and KCNJ11 gene mutations and phenotypes in Korean patients with congenital hyperinsulinism.

PMID 21812132 2011 Abstracts of the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism. Geneva, Switzerland. August 30-September 2, 2011.

PMID 20022885 2010 Interaction between mutations in the slide helix of Kir6.2 associated with neonatal diabetes and neurological symptoms.

PMID 28842488 2017 Conserved functional consequences of disease-associated mutations in the slide helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium channel.

PMID 17855752 2007 A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit.

PMID 16609879 2006 Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype.

PMID 15292329 2004 Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 Gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel.

PMID 15448106 2004 Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy.

PMID 15115830 2004 Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes.

PMID 17652641 2007 A novel mutation causing DEND syndrome: a treatable channelopathy of pancreas and brain.

PMID 15448107 2004 Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients.

PMID 15583126 2004 Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.

PMID 16731833 2006 Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects.

PMID 15580558 2005 KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.

PMID 17213273 2007 Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers.

PMID 15583126 2004 All mutations increased resting whole-cell K(ATP) currents by reducing channel inhibition by ATP, but, in the simulated heterozygous state, mutations causing PNDM alone (R201C) produced smaller K(ATP) currents and less change in ATP sensitivity than mutations associated with severe disease (Q52R and V59G).

PMID 23275527 2013 Genotype and phenotype correlations in 417 children with congenital hyperinsulinism.

PMID 15562009 2005 Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.

PMID 22311976 2012 Role of Derlin-1 protein in proteostasis regulation of ATP-sensitive potassium channels.

PMID 20685672 2010 ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.

PMID 23345197 2013 Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism.

PMID 18250167 2008 Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism.

PMID 16731833 2006 We investigated the functional effects this mutation and another at the same residue (R50P) that led to PNDM in association with developmental delay.

PMID 15583126 2004 Our results also show that mutations in the slide helix of Kir6.2 (V59G) influence the channel kinetics, providing evidence that this domain is involved in Kir channel gating, and suggest that the efficacy of sulfonylurea therapy in PNDM may vary with genotype.

PMID 12524280 2003 Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.

PMID 17446535 2007 Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.

PMID 27908292 2016 Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time.

rs1371185696 in KCNJ11 gene and DIABETES MELLITUS, TRANSIENT NEONATAL, 3 (disorder) PMID 11395395 2001 Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11.

PMID 21812132 2011 Abstracts of the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism. Geneva, Switzerland. August 30-September 2, 2011.

PMID 21422196 2011 Characterization of ABCC8 and KCNJ11 gene mutations and phenotypes in Korean patients with congenital hyperinsulinism.

PMID 15784703 2005 The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus.

PMID 15718250 2005 Relapsing diabetes can result from moderately activating mutations in KCNJ11.

PMID 18250167 2008 Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism.

PMID 22311976 2012 Role of Derlin-1 protein in proteostasis regulation of ATP-sensitive potassium channels.

PMID 23275527 2013 Genotype and phenotype correlations in 417 children with congenital hyperinsulinism.

PMID 15562009 2005 Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.

PMID 23345197 2013 Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism.

PMID 20685672 2010 ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.

PMID 24434300 2014 Long-term follow-up and mutation analysis of 27 chinese cases of congenital hyperinsulinism.

PMID 25639667 2016 Congenital hyperinsulinism in Chinese patients: 5-yr treatment outcome of 95 clinical cases with genetic analysis of 55 cases.

PMID 20049716 2009 Adjacent mutations in the gating loop of Kir6.2 produce neonatal diabetes and hyperinsulinism.

PMID 20589481 2010 Persistent hyperinsulinemic hypoglycemia of infancy due to homozygous KCNJ11 (T294M) mutation.

PMID 27908292 2016 Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time.

PMID 12524280 2003 Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.

PMID 17446535 2007 Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.

rs2074314 in KCNJ11 gene and Diabetes Mellitus, Non-Insulin-Dependent PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 22158537 2011 Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.

PMID 18372903 2008 Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.

PMID 22325160 2012 Large-scale gene-centric meta-analysis across 39 studies identifies type 2 diabetes loci.

PMID 21647700 2011 Genome-wide association and meta-analysis in populations from Starr County, Texas, and Mexico City identify type 2 diabetes susceptibility loci and enrichment for expression quantitative trait loci in top signals.

PMID 28869590 2017 Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.

PMID 22885922 2012 Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.

PMID 24509480 2014 Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

PMID 29632382 2018 Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.

PMID 17463249 2007 Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

PMID 30054458 2018 Genome-wide association analyses identify 143 risk variants and putative regulatory mechanisms for type 2 diabetes.

PMID 23300278 2013 Genome-wide association study identifies a novel locus contributing to type 2 diabetes susceptibility in Sikhs of Punjabi origin from India.

PMID 17463246 2007 Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.

PMID 17463248 2007 A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants.

PMID 19056611 2009 Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome-wide association data.

rs1564865302 in KCNJ11 gene and Hyperglycemia PMID 22701567 2012 Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene.

PMID 21210267 2011 Neonatal diabetes mellitus due to L233F mutation in the KCNJ11 gene.

PMID 27033559 2016 Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes.

PMID 21054355 2011 Permanent neonatal diabetes mellitus--the importance of diabetes differential diagnosis in neonates and infants.

rs104894237 in KCNJ11 gene and Hyperinsulinemic hypoglycemia, familial, 2 PMID 16357843 2006 Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism.

PMID 16332676 2006 A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels.

PMID 7847376 1995 Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy.

PMID 10204114 1999 Molecular biology of adenosine triphosphate-sensitive potassium channels.

PMID 15807877 2005 Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy.

PMID 19357197 2009 Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation causing congenital hyperinsulinism.

PMID 15562009 2005 Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.

PMID 8923010 1996 Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy.

PMID 15998776 2005 Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function.

PMID 18596924 2008 Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations.

PMID 15579781 2004 Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity.

PMID 12364426 2002 Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism.

PMID 21422196 2011 Characterization of ABCC8 and KCNJ11 gene mutations and phenotypes in Korean patients with congenital hyperinsulinism.

PMID 21812132 2011 Abstracts of the Annual Symposium of the Society for the Study of Inborn Errors of Metabolism. Geneva, Switzerland. August 30-September 2, 2011.

PMID 11395395 2001 Unbalanced expression of 11p15 imprinted genes in focal forms of congenital hyperinsulinism: association with a reduction to homozygosity of a mutation in ABCC8 or KCNJ11.

PMID 22311976 2012 Role of Derlin-1 protein in proteostasis regulation of ATP-sensitive potassium channels.

PMID 18250167 2008 Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism.

PMID 20685672 2010 ABCC8 and KCNJ11 molecular spectrum of 109 patients with diazoxide-unresponsive congenital hyperinsulinism.

PMID 23345197 2013 Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism.

PMID 23275527 2013 Genotype and phenotype correlations in 417 children with congenital hyperinsulinism.

PMID 12524280 2003 Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.

PMID 17446535 2007 Mutations in ATP-sensitive K+ channel genes cause transient neonatal diabetes and permanent diabetes in childhood or adulthood.

PMID 27908292 2016 Conservatively treated Congenital Hyperinsulinism (CHI) due to K-ATP channel gene mutations: reducing severity over time.

rs1564865302 in KCNJ11 gene and MATURITY-ONSET DIABETES OF THE YOUNG, TYPE 13 PMID 21210267 2011 Neonatal diabetes mellitus due to L233F mutation in the KCNJ11 gene.

PMID 22701567 2012 Whole-exome sequencing and high throughput genotyping identified KCNJ11 as the thirteenth MODY gene.

PMID 21054355 2011 Permanent neonatal diabetes mellitus--the importance of diabetes differential diagnosis in neonates and infants.

PMID 27033559 2016 Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes.

rs5219 in KCNJ11 gene and Mean blood pressure PMID 27618448 2016 Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.

rs5219 in KCNJ11 gene and Systolic Pressure PMID 27618448 2016 Meta-analysis identifies common and rare variants influencing blood pressure and overlapping with metabolic trait loci.