{{Rsnum
|rsid=5219
|Gene=KCNJ11
|Chromosome=11
|position=17388025
|Orientation=plus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.2741
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|geno1=(C;C)
|geno2=(C;T)
|geno3=(T;T)
|Gene_s=KCNJ11
}}[[rs5219]], also known as E23K, is a SNP in the [[KCNJ11]] gene.

The association between [[type-1 diabetes]] and [[rs5219]] is mentioned as being replicated in {{PMID|17554300|OA=1
}}; there is also a 90% correlation between [[rs5219]] and [[rs5215]].

This SNP is one of 4 relatively common SNPs reported to represent risk for [[type-2 diabetes]] in the DESIR prospective study of 3,877 Caucasian participants. Under an additive model, the odds ratio for the minor (risk) allele (T) is 1.15 (CI: 0.95-1.4, p=0.2, ie not significant). But for the 4 SNPs, each risk allele increased [[type-2 diabetes]] risk by 1.34x (p=2x10e-6), with an odds ratio of 2.48 (CI: 1.59-3.86) for carriers of 4 or more compared to those with one or none (risk alleles).{{PMID|17977958}}

Genotyping of ~4000 Chinese as well a meta-analysis concluded that [[rs5219]] was associated with [[type-2 diabetes]] in Chinese Han and East Asian populations, under a recessive model showing an odds ratio of 1.25 (CI: 1.04-1.5, p=0.017).{{PMID|19498446}}

{{PMID|18162508}} significantly associated p = 0.0034; in 1,630 Japanese subjects with [[type-2 diabetes]] and in 1,064 controls

{{ neighbor
| rsid = 28936678
| distance = 373
}}

{{Venter SNP
|rsid=5219
|allele=C
|frequency=
|uid=1103649619609
|type=homozygous_SNP
|hugo=KCNJ11
|ensembl gene=ENSG00000187486
|ensembl transcript=ENST00000339994
|sift=TOLERATED
|disease=Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes mellitus.
}}

{{PMID Auto
|PMID=19258437
|Title=A Genetic Variant in the IGF2BP2 Gene may Interact with Fetal Malnutrition on Glucose Metabolism.
|OA=1
}}

{{PMID Auto GWAS
|PMID=19056611
|Trait=Type 2 diabetes
|Title=Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data
|RiskAllele=
|Pval=5E-7
|OR=1.19
|ORtxt=[1.11-1.27]
|OA=1
}}
{{PMID Auto GWAS
|PMID=17463246
|Trait=Type 2 diabetes
|Title=Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
|RiskAllele=T
|Pval=7.0000000000000004E-11
|OR=1.14
|ORtxt=[1.10-1.19]
}}
{{PMID Auto GWAS
|PMID=17463248
|Trait=Type 2 diabetes
|Title=A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
|RiskAllele=T
|Pval=7.0000000000000004E-11
|OR=1.14
|ORtxt=[1.10-1.19]
|OA=1
}}
{{PMID Auto
|PMID=18972257
|Title=Comparison of genetic risk in three candidate genes (TCF7L2, PPARG, KCNJ11) with traditional risk factors for type 2 diabetes in a population-based study--the HUNT study
}}

{{omim
|id=600937
|desc=POTASSIUM CHANNEL, INWARDLY RECTIFYING, SUBFAMILY J, MEMBER 11; KCNJ11
|rsnum=5219
}}

{{PharmGKB
|RSID=rs5219
|Name_s=KCNJ11: Lys23Glu
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:20054294
|Annotation=Risk or phenotype-associated allele: G allele. Phenotype: Increased levels of fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) (p < 0.05); and post-repaglinide treatment, GA or AA genotype carries had increased levels of FPG, PPG, and glycated hemoglobin (HbA(1c)) compared with patients with the GG genotype (p < 0.05) Study size: 259 type II diabetes cases and 188 healthy controls. Study population/ethnicity: Chinese. Significance metric(s): p < 0.05. Type of association: GN; PD.
|Drugs=repaglinide
|Drug Classes=
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA165291915
}}

{{PMID Auto
|PMID=20361036
|Title=Gene-gene interactions lead to higher risk for development of type 2 diabetes in an ashkenazi jewish population
|OA=1
}}

{{PharmGKB
|RSID=rs5219
|Name_s=KCNJ11:E23K
|Gene_s=KCNJ11
|Feature=
|Evidence=Web Resource:http://www.pharmgkb.org/search/annotatedGene/kcnj11/variant.jsp
|Annotation=May decrease sensitivity of channel to ATP by altering the charge of the ATP binding region
|Drugs=
|Drug Classes=SULFONAMIDES, UREA DERIVATIVES
|Diseases=
|Curation Level=In-Depth
|PharmGKB Accession ID=PA161145166
}}

{{PharmGKB
|RSID=rs5219
|Name_s=
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:17463246
|Annotation=rs5219 demonstrated association with Type 2 Diabetes in a GWAS of Finnish and Swedish patients and controls.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA162168098
}}

{{PharmGKB
|RSID=rs5219
|Name_s=
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:17463248
|Annotation=In a large Finnish case-control GWAS, rs5219 was found to be associated with susceptibility to Type 2 Diabetes.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA162191363
}}

{{PharmGKB
|RSID=rs5219
|Name_s=
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:19056611; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data. (Initial Sample Size: 1,924 cases, 2,938 controls; Replication Sample Size: 3,757 cases, 5,346 controls); (Region: 11p15.1; Reported Gene(s): KCNJ11; Risk Allele: rs5219-?); (p-value(obese) = 0.0000005).This variant is associated with Type 2 diabetes.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus; Diabetes Mellitus, Type 2
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740295
}}

{{PharmGKB
|RSID=rs5219
|Name_s=
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:19056611; Web Resource:http://www.genome.gov/gwastudies/
|Annotation=GWAS results: Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data. (Initial Sample Size: 1,924 cases, 2,938 controls; Replication Sample Size: 3,757 cases, 5,346 controls); (Region: 11p15.1; Reported Gene(s): KCNJ11; Risk Allele: rs5219-?); (p-value(non-obese)= 0.000000001).This variant is associated with Type 2 diabetes.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus; Diabetes Mellitus, Type 2
|Curation Level=Non-Curated
|PharmGKB Accession ID=PA164740299
}}

{{PharmGKB
|RSID=rs5219
|Name_s=KCNJ11:67A>G, Lys23Glu (E23K)
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:20054294
|Annotation=Risk or phenotype-associated allele: G (23Glu) allele. Phenotype: Baseline clinical characteristic (fasting plasma glucose (p < 0.032)), postprandial plasma glucose (p < 0.014) levels) were significantly increased in T2DM patients with the G (23Glu) allele in a comparison of the GG, GA and AA genotypes. Study size: 259. Study population/ethnicity: Chinese type 2 Diabetes (T2DM) patients. Significance metric(s): p < 0.032. Type of association: GN.
|Drugs=
|Drug Classes=
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA165290948
}}

{{PharmGKB
|RSID=rs5219
|Name_s=KCNJ11:67A>G, Lys23Glu (E23K)
|Gene_s=KCNJ11
|Feature=
|Evidence=PubMed ID:20054294
|Annotation=Risk or phenotype-associated allele: GG (23Glu/Glu) genotype. Phenotype: After 8-week repaglinide treatment, levels of fasting plasma glucose, postprandial plasma glucose, and percent HbA(1c) glycated hemoglobin were significantly lower in T2DM patients with the GG (23Glu/Glu) genotype (n = 18) compared to patients with the AA (23Lys/Lys) and AG (23Lys/Glu) genotypes combined (n = 22) (p < 0.036). Study Size: 40. Study population/ethnicity: Chinese type 2 Diabetes (T2DM) patients with uniform genotype with regard to SLCO1B3 (OATP1B1) T521C. Significance metric(s): p < 0.036. Type of association: GN; PD.
|Drugs=repaglinide
|Drug Classes=
|Diseases=Diabetes Mellitus, Type 2
|Curation Level=Curated
|PharmGKB Accession ID=PA165290949
}}

{{omim
|id=600937
|rsnum=5219
|variant=0014
}}

{{ClinVar
|rsid=5219
|Reversed=0
|FwdREF=T
|FwdALT=C
|REF=T
|ALT=C
|RSPOS=17409572
|CHROM=11
|GMAF=0.2738
|dbSNPBuildID=52
|SSR=0
|SAO=1
|VP=0x05016800000015051e130100
|GENEINFO=KCNJ11:3767
|GENE_NAME=KCNJ11
|GENE_ID=3767
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000011.9:g.17409572T>C
|CLNSRC=GeneReviews; OMIM Allelic Variant
|CLNORIGIN=1
|CLNSRCID=NBK1447; 600937.0014
|CLNSIG=255
|CLNCUI=C1833104; C1833104
|CLNDBN=Diabetes mellitus type 2; Exercise stress response, impaired, association with; Permanent neonatal diabetes mellitus
|Disease=Diabetes mellitus type 2; Exercise stress response; Permanent neonatal diabetes mellitus
|CLNACC=RCV000009214.1; RCV000009215.1; RCV000020356.1
|Tags=PM;PMC;SLO;VLD;G5;HD;GNO;KGPhase1;KGPilot123;KGPROD;OTHERKG;LSD;MTP;OM
|CAF=0.2741; 0.7259
|CLNDSDB=MedGen:OMIM:SNOMED_CT; GeneReviews:MedGen:OMIM:Orphanet:Orphanet
|CLNDSDBID=C0011860:125853:44054006; NBK1447:C1833104:606176:79134:99885
|COMMON=1
}}

{{PMID Auto
|PMID=16733889
|Title=[Association analysis of 30 type 2 diabetes candidate genes in Chinese Han population].
}}

{{PMID Auto
|PMID=16873704
|Title=Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects.
}}

{{PMID Auto
|PMID=17570749
|Title=Genetic prediction of future type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=17786212
|Title=Heterogeneity in meta-analyses of genome-wide association investigations.
|OA=1
}}

{{PMID Auto
|PMID=17903298
|Title=Genome-wide association with diabetes-related traits in the Framingham Heart Study.
|OA=1
}}

{{PMID Auto
|PMID=18224312
|Title=Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.
|OA=1
}}

{{PMID Auto
|PMID=18282109
|Title=Adaptations to climate in candidate genes for common metabolic disorders.
|OA=1
}}

{{PMID Auto
|PMID=18319073
|Title=Using the optimal receiver operating characteristic curve to design a predictive genetic test, exemplified with type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=18423522
|Title=Estimating odds ratios in genome scans: an approximate conditional likelihood approach.
|OA=1
}}

{{PMID Auto
|PMID=18426861
|Title=Association analysis of type 2 diabetes Loci in type 1 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=18498634
|Title=The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.
|OA=1
}}

{{PMID Auto
|PMID=18591388
|Title=Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk.
|OA=1
}}

{{PMID Auto
|PMID=18678618
|Title=Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.
|OA=1
}}

{{PMID Auto
|PMID=18689695
|Title=Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR).
|OA=1
}}

{{PMID Auto
|PMID=18689899
|Title=Exchangeable models of complex inherited diseases.
|OA=1
}}

{{PMID Auto
|PMID=18694974
|Title=Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
|OA=1
}}

{{PMID Auto
|PMID=18782870
|Title=Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008.
|OA=1
}}

{{PMID Auto
|PMID=18852197
|Title=Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.
|OA=1
}}

{{PMID Auto
|PMID=19002430
|Title=Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean population.
}}

{{PMID Auto
|PMID=19020323
|Title=Genotype score in addition to common risk factors for prediction of type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=19033397
|Title=Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening.
|OA=1
}}

{{PMID Auto
|PMID=19207020
|Title=Meta-analysis in genome-wide association studies.
|OA=1
}}

{{PMID Auto
|PMID=19279076
|Title=Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men.
|OA=1
}}

{{PMID Auto
|PMID=19309528
|Title=Specific and complete human genome amplification with improved yield achieved by phi29 DNA polymerase and a novel primer at elevated temperature.
|OA=1
}}

{{PMID Auto
|PMID=19323962
|Title=Genome-wide association studies in type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=19324937
|Title=Previously associated type 2 diabetes variants may interact with physical activity to modify the risk of impaired glucose regulation and type 2 diabetes: a study of 16,003 Swedish adults.
|OA=1
}}

{{PMID Auto
|PMID=19341491
|Title=Genome-based prediction of common diseases: methodological considerations for future research.
|OA=1
}}

{{PMID Auto
|PMID=19368707
|Title=Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study.
|OA=1
}}

{{PMID Auto
|PMID=19401414
|Title=Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.
|OA=1
}}

{{PMID Auto
|PMID=19455305
|Title=No association of multiple type 2 diabetes loci with type 1 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=19460916
|Title=Genetic architecture of type 2 diabetes: recent progress and clinical implications.
|OA=1
}}

{{PMID Auto
|PMID=19502414
|Title=Association of 18 confirmed susceptibility loci for type 2 diabetes with indices of insulin release, proinsulin conversion, and insulin sensitivity in 5,327 nondiabetic Finnish men.
|OA=1
}}

{{PMID Auto
|PMID=19602701
|Title=Underlying genetic models of inheritance in established type 2 diabetes associations.
|OA=1
}}

{{PMID Auto
|PMID=19862325
|Title=PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.
|OA=1
}}

{{PMID Auto
|PMID=19956539
|Title=How many genetic variants remain to be discovered?
|OA=1
}}

{{PMID Auto
|PMID=20017978
|Title=Influence of control selection in genome-wide association studies: the example of diabetes in the Framingham Heart Study.
|OA=1
}}

{{PMID Auto
|PMID=20018041
|Title=The effect of multiple genetic variants in predicting the risk of type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=20043853
|Title=Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus.
|OA=1
}}

{{PMID Auto
|PMID=20049090
|Title=Association between type 2 diabetes loci and measures of fatness.
|OA=1
}}

{{PMID Auto
|PMID=20075150
|Title=Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.
|OA=1
}}

{{PMID Auto
|PMID=20079163
|Title=Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population.
}}

{{PMID Auto
|PMID=20144327
|Title=A genomics study of type 2 diabetes mellitus in U.S. Air Force personnel.
|OA=1
}}

{{PMID Auto
|PMID=20161779
|Title=Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.
|OA=1
}}

{{PMID Auto
|PMID=20424228
|Title=Impact of common variants of PPARG, KCNJ11, TCF7L2, SLC30A8, HHEX, CDKN2A, IGF2BP2, and CDKAL1 on the risk of type 2 diabetes in 5,164 Indians.
|OA=1
}}

{{PMID Auto
|PMID=20712903
|Title=Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study.
|OA=1
}}

{{PMID Auto
|PMID=21278902
|Title=Genetic risk profiling for prediction of type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=21283728
|Title=Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.
|OA=1
}}

{{PMID Auto
|PMID=21573802
|Title=Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals.
}}

{{PMID Auto
|PMID=21602532
|Title=Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies.
}}

{{PMID Auto
|PMID=22082043
|Title=The effect of KCNJ11 polymorphism on the risk of type 2 diabetes: a global meta-analysis based on 49 case-control studies.
}}

{{PMID Auto
|PMID=22377712
|Title=Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography.
}}

{{GET Evidence
|gene=KCNJ11
|aa_change=Lys23Glu
|aa_change_short=K23E
|impact=protective
|qualified_impact=Low clinical importance, Likely protective
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs5219
|overall_frequency_n=7941
|overall_frequency_d=10758
|overall_frequency=0.738148
|n_genomes=46
|n_genomes_annotated=0
|n_haplomes=78
|n_articles=3
|n_articles_annotated=3
|qualityscore_in_silico=1
|qualitycomment_in_silico=Y
|qualityscore_case_control=5
|qualitycomment_case_control=Y
|qualityscore_familial=0
|qualityscore_severity=3
|qualityscore_treatability=4
|gene_in_genetests=Y
|in_gwas=Y
|in_pharmgkb=Y
|genetests_testable=Y
|genetests_reviewed=Y
|nblosum100=0
|autoscore=4
|webscore=N
|n_web_uneval=6
|variant_evidence=0
|clinical_importance=1
|summary_short=This variant is associated with decreased risk of type 2 diabetes. It is unclear whether this variant has additive effects, or acts in a dominant or recessive manner. Assuming diabetes has a lifetime risk of 36%, we estimate a decreased risk of around 1-2% per copy of this variant.
}}

{{PMID Auto
|PMID=23029294
|Title=Meta-analysis of the relationship between common type 2 diabetes risk gene variants with gestational diabetes mellitus
|OA=1
}}

{{PMID Auto
|PMID=23690305
|Title=Genetic variants and the risk of gestational diabetes mellitus: a systematic review
}}

{{PMID Auto
|PMID=22749234
|Title=Contribution of common variants of ENPP1, IGF2BP2, KCNJ11, MLXIPL, PPARγ, SLC30A8 and TCF7L2 to the risk of type 2 diabetes in Lebanese and Tunisian Arabs
}}

{{PMID Auto
|PMID=23298195
|Title=Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population.
}}

{{PMID Auto
|PMID=23458876
|Title=ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis.
}}

{{PMID Auto
|PMID=23462794
|Title=Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.
|OA=1
}}

{{PMID Auto
|PMID=23544998
|Title=Association of TRPC1 gene polymorphisms with type 2 diabetes and diabetic nephropathy in Han Chinese population.
|OA=1
}}

{{PMID Auto
|PMID=9867219
|Title=Missense mutations in the pancreatic islet beta cell inwardly rectifying K+ channel gene (KIR6.2/BIR): a meta-analysis suggests a role in the polygenic basis of Type II diabetes mellitus in Caucasians.
}}

{{PMID Auto
|PMID=15579791
|Title=Polymorphisms of the SUR1 (ABCC8) and Kir6.2 (KCNJ11) genes predict the conversion from impaired glucose tolerance to type 2 diabetes. The Finnish Diabetes Prevention Study.
}}

{{PMID Auto
|PMID=15797964
|Title=Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.
}}

{{PMID Auto
|PMID=17463249
|Title=Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
|OA=1
}}

{{PMID Auto
|PMID=25247988
|Title=Population Specific Impact of Genetic Variants in KCNJ11 Gene to Type 2 Diabetes: A Case-Control and Meta-Analysis Study
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | HumanOmni1Quad}}