PharmGKB: The Pharmacogenomics Knowledge Base

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

Overview

Alternate Names: ATP-sensitive inward rectifier potassium channel 11; beta-cell inward rectifier subunit; inwardly rectifying potassium channel KIR6.2; potassium inwardly-rectifying channel J11
Alternate Symbols: BIR; HHF2; IKATP; KIR6.2; Kir6.2; MGC133230; PHHI; TNDM3
PharmGKB Accession Id: PA217

Details

Cytogenetic Location: chr11 : p15.1
GP mRNA Boundary†: chr11 : 17363371 - 17366782
GP Gene Boundary†: chr11 : 17360371 - 17376782
Strand: minus
Product Name: ATP-sensitive inward rectifier potassium channel 11, beta-cell inward rectifier subunit, inwardly rectifying potassium channel KIR6.2, potassium inwardly-rectifying channel J11, potassium inwardly-rectifying channel, subfamily J, member 11
† 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.

Introduction

View Full VIP Annotation

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 ATPchannels 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 ATPchannel, Kir6.2 (the ATP-sensor and channel pore) and the sulfonylurea receptor (SUR1), and mapped both genes to a common region on chromosome 11 [PMID: 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 it 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 [PMID: 15842514]. KCNJ11variation is implicated as a risk factor for type 2 diabetes based on the results of numerous clinical and population-based association studies [PMID:]. The literature for ABCC8 is not as consistent, although variants in the KCNJ11 and ABCC8 are tightly linked. [PMID: 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 [PMID: 16595597]. Additionally, patients with rare activating variants in KCNJ11 may be able to discontinue insulin after starting oral sulfonylurea therapy. [PMID: 16885550]

In-Depth Annotations (In-Depth Annotation)

  1. rs5219 at chr11:17366148 in KCNJ11
    May decrease sensitivity of channel to ATP by altering the charge of the ATP binding region
    Variant Name:
    KCNJ11:E23K
    Related Drugs:
    sulfonamides, urea derivatives
    Evidence:
    http://www.pharmgkb.org/.../variant.jsp

Curated Annotations (Curated Annotation)

  1. rs5219 at chr11:17366148 in KCNJ11
    rs5219 demonstrated association with Type 2 Diabetes in a GWAS of Finnish and Swedish patients and controls.
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:17463246
  2. rs5219 at chr11:17366148 in KCNJ11
    In a large Finnish case-control GWAS, rs5219 was found to be associated with susceptibility to Type 2 Diabetes.
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:17463248

Non-Curated Annotations (Non-Curated Annotation)

  1. rs5219 at chr11:17366148 in KCNJ11
    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= 0.0000005).This variant is associated with Type 2 diabetes.
    Related Diseases:
    Diabetes Mellitus, Diabetes Mellitus, Type 2
    Evidence:
    PMID:19056611
    http://www.genome.gov/gwastudies/
  2. rs5219 at chr11:17366148 in KCNJ11
    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= 0.000000001).This variant is associated with Type 2 diabetes.
    Related Diseases:
    Diabetes Mellitus, Diabetes Mellitus, Type 2
    Evidence:
    PMID:19056611
    http://www.genome.gov/gwastudies/
Variant names are different names that have been used in the literature and other resources to refer to the same variant. Non-curated variant information is accumulated solely by computational methods and has not been verified by the scientific staff at PharmGKB.

Non-Curated Information

A list of non-curated publications that mention this gene along with other genes is available.

Curated Information

The following drugs are in curated knowledge about this gene.

  Drug Class Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
antiarrhythmics, class i and iii
  •   
  • PD
  •   
  • FA
  •   
Publications, Pathways
No phenotype data No genotype data Literature annotations available Not annotated
sulfonamides, urea derivatives
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
amiodarone
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
arsenic trioxide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data No literature annotations Not annotated
chlorpropamide
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
cisapride
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
diazoxide
  •   
  •   
  •   
  • FA
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Not annotated
disopyramide
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
dofetilide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
droperidol
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
flecainide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
gliclazide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
glimepiride
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
glipizide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
halofantrine
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
haloperidol
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
ibutilide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
lidocaine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
mesoridazine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
methadone
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
mexiletine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
nateglinide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
pentamidine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
pimozide
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
procainamide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
propafenone
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
quinidine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
repaglinide
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available Genotype Data Available Literature annotations available Not annotated
sotalol
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
sparfloxacin
  •   
  • PD
  •   
  •   
  •   
Pathways
Phenotype data available No genotype data Literature annotations available Not annotated
thioridazine
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data No literature annotations Not annotated
tocainide
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
tolbutamide
  •   
  • PD
  •   
  •   
  •   
Pathways

Non-Curated Information

A list of non-curated publications that mention this gene along with other drugs is available.

Curated Information

The following diseases are in curated knowledge about this gene.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus
  •   
  • PD
  •   
  •   
  •   
Pathways
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 1
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 2
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes, Permanent Neonatal (PNDM)
  • CO
  •   
  •   
  • FA
  • GN
Publications

Non-Curated Information

A list of non-curated publications that mention this gene along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Adaptations to Climate in Candidate Genes for Common Metabolic Disorders

Downloads

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LinkOuts

Entrez Gene ID:
3767
OMIM Accession:
125853
600937
601820
606176
610582
UCSC Genome Browser ID:
NM_000525
Ref Seq NM Accession:
NM_000525
Ref Seq NP Accession:
AAH40617
AAH64497
AAI12359
BAA09131
BAG37449
EAW68438
NP_000516
Q14654
Q8IW96
Ref Seq NT Accession:
AC_000054
AC_000143
NC_000011
NT_009237
NW_001838022
NW_925006
Ensembl ID:
ENSG00000187486
GenAtlas ID:
KCNJ11
GeneCard ID:
KCNJ11
SOURCE ID:
KCNJ11
MutDB ID:
KCNJ11
PromoLign ID:
ortho_4725
HuGE ID:
KCNJ11
Comparative Toxicogenomics Acc ID:
3767
ModBase:
Q14654

Common Searches

Non-Curated Publications

A list of non-curated publications that mention this gene is available.

The PharmGKB is financially supported by the NIH/ NIGMS and is managed at Stanford University (U01GM61374).
©2001-2010 PharmGKB.