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From SNPedia

Geno Mag Summary
(C;C) 0 normal
(C;T) 1.5 1.3x increased risk for type-2 diabetes
(T;T) 2.5 2.5x increased risk for type-2 diabetes
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs5219
23andMe allrs5219
SNP Nexus

GWAS Ctlgrs5219
Max Magnitude2.5
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 17554300OA-icon.png]; 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


Venter snp
Source plos
Gene KCNJ11
allele C
HuRef 1103649619609
Disease Association Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as type II diabetes mellitus.

[PMID 19258437OA-icon.png] A Genetic Variant in the IGF2BP2 Gene may Interact with Fetal Malnutrition on Glucose Metabolism.

GWAS snp
PMID [PMID 19056611OA-icon.png]
Trait Type 2 diabetes
Title Adiposity-related heterogeneity in patterns of type 2 diabetes susceptibility observed in genome wide association data
Risk Allele
P-val 5E-7
Odds Ratio 1.19 [1.11-1.27]
GWAS snp
PMID [PMID 17463246]
Trait Type 2 diabetes
Title Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels
Risk Allele T
P-val 7.0000000000000004E-11
Odds Ratio 1.14 [1.10-1.19]
GWAS snp
PMID [PMID 17463248OA-icon.png]
Trait Type 2 diabetes
Title A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants
Risk Allele T
P-val 7.0000000000000004E-11
Odds Ratio 1.14 [1.10-1.19]

[PMID 18972257] 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

[PMID 20361036OA-icon.png] Gene-gene interactions lead to higher risk for development of type 2 diabetes in an ashkenazi jewish population


Risk rs5219(C;C)
Alt rs5219(C;C)
Reference rs5219(T;T)
Significance Other
Disease Diabetes mellitus type 2 Exercise stress response Permanent neonatal diabetes mellitus not specified
Variation info
Gene KCNJ11
CLNDBN Diabetes mellitus type 2 Exercise stress response, impaired, association with Permanent neonatal diabetes mellitus not specified
Reversed 0
HGVS NC_000011.10:g.17388025T>C
CLNSRC OMIM Allelic Variant
CLNACC RCV000009214.2, RCV000009215.2, RCV000020356.1, RCV000146116.1,

[PMID 16733889] [Association analysis of 30 type 2 diabetes candidate genes in Chinese Han population].

[PMID 16873704] Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects.

[PMID 17570749OA-icon.png] Genetic prediction of future type 2 diabetes.

[PMID 17786212OA-icon.png] Heterogeneity in meta-analyses of genome-wide association investigations.

[PMID 17903298OA-icon.png] Genome-wide association with diabetes-related traits in the Framingham Heart Study.

[PMID 18224312OA-icon.png] Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatment.

[PMID 18282109OA-icon.png] Adaptations to climate in candidate genes for common metabolic disorders.

[PMID 18319073OA-icon.png] Using the optimal receiver operating characteristic curve to design a predictive genetic test, exemplified with type 2 diabetes.

[PMID 18423522OA-icon.png] Estimating odds ratios in genome scans: an approximate conditional likelihood approach.

[PMID 18426861OA-icon.png] Association analysis of type 2 diabetes Loci in type 1 diabetes.

[PMID 18498634OA-icon.png] The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies.

[PMID 18591388OA-icon.png] Assessing the combined impact of 18 common genetic variants of modest effect sizes on type 2 diabetes risk.

[PMID 18678618OA-icon.png] Comprehensive association study of type 2 diabetes and related quantitative traits with 222 candidate genes.

[PMID 18689695OA-icon.png] Predicting diabetes: clinical, biological, and genetic approaches: data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR).

[PMID 18689899OA-icon.png] Exchangeable models of complex inherited diseases.

[PMID 18694974OA-icon.png] Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.

[PMID 18782870OA-icon.png] Clinical review: the genetics of type 2 diabetes: a realistic appraisal in 2008.

[PMID 18852197OA-icon.png] Metabolic and cardiovascular traits: an abundance of recently identified common genetic variants.

[PMID 19002430] 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 19020323OA-icon.png] Genotype score in addition to common risk factors for prediction of type 2 diabetes.

[PMID 19033397OA-icon.png] Replication study of candidate genes associated with type 2 diabetes based on genome-wide screening.

[PMID 19207020OA-icon.png] Meta-analysis in genome-wide association studies.

[PMID 19279076OA-icon.png] Genetic predisposition, Western dietary pattern, and the risk of type 2 diabetes in men.

[PMID 19309528OA-icon.png] Specific and complete human genome amplification with improved yield achieved by phi29 DNA polymerase and a novel primer at elevated temperature.

[PMID 19323962OA-icon.png] Genome-wide association studies in type 2 diabetes.

[PMID 19324937OA-icon.png] 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.

[PMID 19341491OA-icon.png] Genome-based prediction of common diseases: methodological considerations for future research.

[PMID 19368707OA-icon.png] Contribution of type 2 diabetes associated loci in the Arabic population from Tunisia: a case-control study.

[PMID 19401414OA-icon.png] Confirmation of multiple risk Loci and genetic impacts by a genome-wide association study of type 2 diabetes in the Japanese population.

[PMID 19455305OA-icon.png] No association of multiple type 2 diabetes loci with type 1 diabetes.

[PMID 19460916OA-icon.png] Genetic architecture of type 2 diabetes: recent progress and clinical implications.

[PMID 19502414OA-icon.png] 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.

[PMID 19602701OA-icon.png] Underlying genetic models of inheritance in established type 2 diabetes associations.

[PMID 19862325OA-icon.png] PPARG, KCNJ11, CDKAL1, CDKN2A-CDKN2B, IDE-KIF11-HHEX, IGF2BP2 and SLC30A8 are associated with type 2 diabetes in a Chinese population.

[PMID 19956539OA-icon.png] How many genetic variants remain to be discovered?

[PMID 20017978OA-icon.png] Influence of control selection in genome-wide association studies: the example of diabetes in the Framingham Heart Study.

[PMID 20018041OA-icon.png] The effect of multiple genetic variants in predicting the risk of type 2 diabetes.

[PMID 20043853OA-icon.png] Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus.

[PMID 20049090OA-icon.png] Association between type 2 diabetes loci and measures of fatness.

[PMID 20075150OA-icon.png] Utility of genetic and non-genetic risk factors in prediction of type 2 diabetes: Whitehall II prospective cohort study.

[PMID 20079163] Effect of genetic variants in KCNJ11, ABCC8, PPARG and HNF4A loci on the susceptibility of type 2 diabetes in Chinese Han population.

[PMID 20144327OA-icon.png] A genomics study of type 2 diabetes mellitus in U.S. Air Force personnel.

[PMID 20161779OA-icon.png] Investigation of type 2 diabetes risk alleles support CDKN2A/B, CDKAL1, and TCF7L2 as susceptibility genes in a Han Chinese cohort.

[PMID 20424228OA-icon.png] 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.

[PMID 20712903OA-icon.png] Obesity and diabetes genes are associated with being born small for gestational age: results from the Auckland Birthweight Collaborative study.

[PMID 21278902OA-icon.png] Genetic risk profiling for prediction of type 2 diabetes.

[PMID 21283728OA-icon.png] Genetic variants of diabetes risk and incident cardiovascular events in chronic coronary artery disease.

[PMID 21573802] Association between KCNJ11 gene polymorphisms and risk of type 2 diabetes mellitus in East Asian populations: a meta-analysis in 42,573 individuals.

[PMID 21602532OA-icon.png] Type 2 diabetes risk variants and colorectal cancer risk: the Multiethnic Cohort and PAGE studies.

[PMID 22082043] The effect of KCNJ11 polymorphism on the risk of type 2 diabetes: a global meta-analysis based on 49 case-control studies.

[PMID 22377712] Association between type 2 diabetes genetic susceptibility loci and visceral and subcutaneous fat area as determined by computed tomography.

GET Evidence
aa_change Lys23Glu
aa_change_short K23E
impact protective
qualified_impact Low clinical importance, Likely protective
overall_frequency 0.738148
summary 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 23029294OA-icon.png] Meta-analysis of the relationship between common type 2 diabetes risk gene variants with gestational diabetes mellitus

[PMID 23690305OA-icon.png] Genetic variants and the risk of gestational diabetes mellitus: a systematic review

[PMID 22749234] 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 23298195] Association study of genetic variants of 17 diabetes-related genes/loci and cardiovascular risk and diabetic nephropathy in the Chinese She population.

[PMID 23458876] ACE I/D and MTHFR C677T polymorphisms are significantly associated with type 2 diabetes in Arab ethnicity: a meta-analysis.

[PMID 23462794OA-icon.png] Identification of CpG-SNPs associated with type 2 diabetes and differential DNA methylation in human pancreatic islets.

[PMID 23544998OA-icon.png] Association of TRPC1 gene polymorphisms with type 2 diabetes and diabetic nephropathy in Han Chinese population.

[PMID 9867219] 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 15579791] 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 15797964] Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes.

[PMID 17463249OA-icon.png] Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.

[PMID 25247988OA-icon.png] Population Specific Impact of Genetic Variants in KCNJ11 Gene to Type 2 Diabetes: A Case-Control and Meta-Analysis Study