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
  3. rs5219 at chr11:17366148 in KCNJ11
    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.
    Variant Name:
    KCNJ11: Lys23Glu
    Related Drugs:
    repaglinide
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:20054294
  4. rs5219 at chr11:17366148 in KCNJ11
    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.
    Variant Name:
    KCNJ11:67A>G, Lys23Glu (E23K)
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:20054294
  5. rs5219 at chr11:17366148 in KCNJ11
    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.
    Variant Name:
    KCNJ11:67A>G, Lys23Glu (E23K)
    Related Drugs:
    repaglinide
    Related Diseases:
    Diabetes Mellitus, Type 2
    Evidence:
    PMID:20054294

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(obese) = 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(non-obese)= 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
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
sulfonamides, urea derivatives
  • CO
  • PD
  •   
  •   
  • GN
Publications, Variants
  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
diazoxide
  •   
  •   
  •   
  • FA
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
repaglinide
  •   
  • PD
  • PK
  •   
  •   
Publications, Variants

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, Type 1
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Diabetes Mellitus, Type 2
  • CO
  • PD
  • PK
  •   
  • 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
IUPHAR Receptor ID:
Kir6.2 (442)

Common Searches

Non-Curated Publications

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

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