Gene:
KCNJ11
potassium inwardly-rectifying channel, subfamily J, member 11

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PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the table.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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This is a non-comprehensive list of genetic tests with pharmacogenetics relevance, typically submitted by the manufacturer and manually curated by PharmGKB. The information listed is provided for educational purposes only and does not constitute an endorsement of any listed test or manufacturer.

A more complete listing of genetic tests is found at the Genetic Testing Registry (GTR).

PGx Test Variants Assayed Related Drugs?

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page on the appropriate tab.

Links in the "Drugs" column lead to PharmGKB Drug Pages.

Variant?
(138)
Alternate Names / Tag SNPs ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available No Clinical Annotations available VA
rs5215 1009G>A, 17348630C>T, 17408630C>T, 6577G>A, 748G>A, Val250Ile, Val337Ile
C > T
Missense
Val250Ile
rs5219 -16-179A>G, 17349572T>C, 17409572T>C, 5635A>G, 67A>G, E23K, KCNJ11: Lys23Glu, KCNJ11:67A>G, KCNJ11:E23K, Lys23Glu
T > C
Intronic
Lys23Glu
No VIP available No Clinical Annotations available VA
rs757110 17358477C>A, 17418477C>A, 4105G>T, 84973G>T, Ala1369Ser
C > A
Missense
Ala1369Ser
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 138

Overview

Alternate Names:  None
Alternate Symbols:  BIR; Kir6.2
PharmGKB Accession Id: PA217

Details

Cytogenetic Location: chr11 : p15.1 - p15.1
GP mRNA Boundary: chr11 : 17406795 - 17410878
GP Gene Boundary: chr11 : 17403795 - 17420878
Strand: minus
The mRNA boundaries are calculated using the gene's default feature set from NCBI, mapped onto the UCSC Golden Path. PharmGKB sets gene boundaries by expanding the mRNA boundaries by no less than 10,000 bases upstream (5') and 3,000 bases downstream (3') to allow for potential regulatory regions.

Note: The KCNJ11 gene is found on the minus chromosomal strand. Please note that for standardization, the PharmGKB presents all allele base pairs on the positive chromosomal strand; therefore the alleles within our variant annotations will differ (in a complementary manner) from those in this VIP summary that are given on the minus strand as reported in the literature.

The inwardly rectifying, ATP-sensitive potassium channel (K ATP) was first identified in cardiac muscle, but it is also expressed in pancreatic Beta-cells, central nervous system tissue, skeletal muscle, and smooth muscle. In the pancreas, the K ATP channels close when intracellular glucose levels increase. The cessation of K+ efflux depolarizes the Beta-cell membrane, which activates voltage-gated calcium channels and facilitates insulin secretion. Sulfonylureas exert their hypoglycemic effect by inhibiting the K ATP channel.

Inagaki et al. cloned the two subunits that form the K ATP channel, Kir6.2 (the ATP-sensor and channel pore) and the sulfonylurea receptor (SUR1), and mapped both genes to a common region on chromosome 11 [Article:7502040]. KCNJ11 is an intronless gene that codes for the 390 amino acid Kir6.2 subunit. KCNJ11 is approximately 3.4 kilobases in size and lies approximately 4.5 kilobases upstream from the gene encoding SUR1 (ABCC8).

Twenty validated SNPs are present in KCNJ11, as reported in dbSNP, but the functional consequences of most are unknown. The most widely studied variant is a G to A substitution at nucleotide 635, which results in a change from a glutamate residue in position 23 to lysine (E23K). This substitution decreases the sensitivity of the potassium channel to ATP and thus affects insulin secretion [Article:15842514]. KCNJ11 variation is implicated as a risk factor for type 2 diabetes based on the results of numerous clinical and population-based association studies. The literature for ABCC8 is not as consistent, although variants in the KCNJ11 and ABCC8 are tightly linked [Articles:12540637, 12540638, 15579791, 15842514, 12540637 15579791, 15111507, 15797964].

The primary target of sulfonylureas is the K ATP channel; therefore, KCNJ11 variation may influence the outcome of sulfonylurea treatment in type 2 diabetes [Article:16595597]. Additionally, patients with rare activating variants in KCNJ11 may be able to discontinue insulin after starting oral sulfonylurea therapy [Article:16885550].

Citation
M. Whirl-Carrillo, E.M. McDonagh, J. M. Hebert, L. Gong, K. Sangkuhl, C.F. Thorn, R.B. Altman and T.E. Klein. "Pharmacogenomics Knowledge for Personalized Medicine" Clinical Pharmacology & Therapeutics (2012) 92(4): 414-417. Full text
History

Submitted by Daniel Gonzalez, Michael Pacanowski, Julie A. Johnson (PEAR)

Variant Summaries rs5219
Drugs
Diseases

PharmGKB Curated Pathways

Pathways created internally by PharmGKB based primarily on literature evidence.

  1. Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics
    Representation of anti-diabetic drugs repaglinide, nateglinide and sulfonylurea effects on insulin secretion in pancreatic cells.
  1. Antiarrhythmic Pathway, Pharmacodynamics
    Pharmacodynamic pathway of antiarrhythmic drugs in a stylized cardiac myocyte.

External Pathways

Links to non-PharmGKB pathways.

  1. FOXA2 and FOXA3 transcription factor networks - (Pathway Interaction Database NCI-Nature Curated)
  2. Glucose Regulation of Insulin Secretion - (Reactome via Pathway Interaction Database)
No related genes are available

Curated Information ?

Curated Information ?

Publications related to KCNJ11: 31

No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
CYP2C9, KCNJ11 and ABCC8 polymorphisms and the response to sulphonylurea treatment in type 2 diabetes patients. European journal of clinical pharmacology. 2014. Klen Jasna, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
SGLT2: a potential target for the pharmacogenetics of Type 2 diabetes?. Pharmacogenomics. 2013. Tönjes Anke, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
KCNJ11 gene E23K variant and therapeutic response to sulfonylureas. European journal of internal medicine. 2012. Javorsky Martin, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients. Acta pharmacologica Sinica. 2011. Duan Rui-feng, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
ABCC8 polymorphism (Ser1369Ala): influence on severe hypoglycemia due to sulfonylureas. Pharmacogenomics. 2010. Sato Ryosuke, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Robust replication of genotype-phenotype associations across multiple diseases in an electronic medical record. American journal of human genetics. 2010. Ritchie Marylyn D, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
KCNJ11 Lys23Glu and TCF7L2 rs290487(C/T) polymorphisms affect therapeutic efficacy of repaglinide in Chinese patients with type 2 diabetes. Clinical pharmacology and therapeutics. 2010. Yu M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Influence of genetic polymorphisms on the pharmacokinetics and pharmaco-dynamics of sulfonylurea drugs. Current drug metabolism. 2009. Xu Hongmei, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Rare variants of IFIH1, a gene implicated in antiviral responses, protect against type 1 diabetes. Science (New York, N.Y.). 2009. Nejentsev Sergey, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Clinical risk factors, DNA variants, and the development of type 2 diabetes. The New England journal of medicine. 2008. Lyssenko Valeriya, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genotype score in addition to common risk factors for prediction of type 2 diabetes. The New England journal of medicine. 2008. Meigs James B, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Permanent neonatal diabetes caused by dominant, recessive, or compound heterozygous SUR1 mutations with opposite functional effects. American journal of human genetics. 2007. Ellard Sian, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science (New York, N.Y.). 2007. Scott Laura J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science (New York, N.Y.). 2007. Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Pharmacogenetics of glucose-lowering drug treatment: a systematic review. Molecular diagnosis & therapy. 2007. Bozkurt Ozlem, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
KCNJ11 gene knockout of the Kir6.2 KATP channel causes maladaptive remodeling and heart failure in hypertension. Human molecular genetics. 2006. Kane Garvan C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. The New England journal of medicine. 2006. Pearson Ewan R, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
A heterozygous activating mutation in the sulphonylurea receptor SUR1 (ABCC8) causes neonatal diabetes. Human molecular genetics. 2006. Proks Peter, et al. PubMed
The E23K variant of KCNJ11 encoding the pancreatic beta-cell adenosine 5'-triphosphate-sensitive potassium channel subunit Kir6.2 is associated with an increased risk of secondary failure to sulfonylurea in patients with type 2 diabetes. The Journal of clinical endocrinology and metabolism. 2006. Sesti Giorgio, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Analysis of separate and combined effects of common variation in KCNJ11 and PPARG on risk of type 2 diabetes. The Journal of clinical endocrinology and metabolism. 2005. Hansen Sara K, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Common variants in the ATP-sensitive K+ channel genes KCNJ11 (Kir6.2) and ABCC8 (SUR1) in relation to glucose intolerance: population-based studies and meta-analyses. Diabetic medicine : a journal of the British Diabetic Association. 2005. van Dam R M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Current status of the E23K Kir6.2 polymorphism: implications for type-2 diabetes. Human genetics. 2005. Riedel Michael J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
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. The Journal of clinical endocrinology and metabolism. 2004. Laukkanen Olli, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Haplotype structure and genotype-phenotype correlations of the sulfonylurea receptor and the islet ATP-sensitive potassium channel gene region. Diabetes. 2004. Florez Jose C, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Candidate gene association study in type 2 diabetes indicates a role for genes involved in beta-cell function as well as insulin action. PLoS biology. 2003. Barroso Inês, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes. Diabetes. 2003. Gloyn Anna L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
The E23K variant of Kir6.2 associates with impaired post-OGTT serum insulin response and increased risk of type 2 diabetes. Diabetes. 2003. Nielsen Eva-Maria D, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
The role of NH2-terminal positive charges in the activity of inward rectifier KATP channels. The Journal of general physiology. 2002. Cukras C A, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53). Diabetic medicine : a journal of the British Diabetic Association. 2001. Gloyn A L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in while Caucasian subjects or evidence of abnormal function when expressed in vitro. Diabetologia. 1996. Sakura H, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor. Science (New York, N.Y.). 1995. Inagaki N, et al. PubMed

LinkOuts

UniProtKB:
B2RC52_HUMAN (B2RC52)
B4DWI4_HUMAN (B4DWI4)
Ensembl:
ENSG00000187486
GenAtlas:
KCNJ11
GeneCard:
KCNJ11
MutDB:
KCNJ11
ALFRED:
LO132999H
HuGE:
KCNJ11
Comparative Toxicogenomics Database:
3767
ModBase:
Q14654
IUPHAR Receptor:
Kir6.2 (442)
HGNC:
6257

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