- Please check and comment entries here.
Potassium voltage-gated channel subfamily J member 11
The KCNJ11 gene provides instructions for making parts (subunits) of the ATP-sensitive potassium (K-ATP) channel. Each K-ATP channel consists of eight subunits. Four subunits are produced from the KCNJ11 gene, and four are produced from another gene called ABCC8.
K-ATP channels are found in beta cells, which are cells in the pancreas that secrete the hormone insulin. The K-ATP channels are embedded in cell membranes, where they open and close in response to the amount of glucose in the bloodstream. Glucose is a simple sugar and the primary energy source for most cells in the body. Closure of the K-ATP channels in response to increased glucose triggers the release of insulin out of beta cells and into the bloodstream, which helps control blood sugar levels.
2. Health Conditions Related to Genetic Changes
2.1. Congenital Hyperinsulinism
More than 30 mutations in the KCNJ11 gene have been found to cause congenital hyperinsulinism. This condition causes frequent episodes of low blood sugar (hypoglycemia), decreased energy, and irritability. Most of these mutations change single protein building blocks (amino acids) in the protein sequence, reducing or preventing activity of the K-ATP channels. Loss of K-ATP channel function leads to the constant release of insulin from beta cells. As a result, glucose is rapidly removed from the bloodstream. Without treatment, the hypoglycemia caused by congenital hyperinsulinism may result in serious complications such as intellectual disability and seizures.
2.2. Permanent Neonatal Diabetes Mellitus
At least 30 mutations in the KCNJ11 gene have been identified in people with permanent neonatal diabetes mellitus. Individuals with this condition often have a low birth weight and develop increased blood sugar (hyperglycemia) within the first 6 months of life.
KCNJ11 gene mutations that cause permanent neonatal diabetes mellitus change single amino acids in the protein sequence. These mutations result in K-ATP channels that do not close, leading to reduced insulin secretion from beta cells and impaired blood sugar control.
2.3. Other Disorders
Other KCNJ11 gene mutations that have a relatively mild effect on K-ATP channel function as compared to that seen in permanent neonatal diabetes mellitus (see above) cause a condition called transient neonatal diabetes mellitus. Infants with this condition have hyperglycemia during the first 6 months of life, but their blood sugar returns to normal by age 18 months. However, affected individuals usually develop hyperglycemia again during adolescence or early adulthood. As in permanent neonatal diabetes mellitus, KCNJ11 gene mutations that cause transient neonatal diabetes mellitus also interfere with K-ATP channel closure and lead to a reduction in insulin secretion.
A normal variation (polymorphism) in the KCNJ11 gene is associated with an increased risk of type 2 diabetes, the most common form of diabetes. This variant leads to a change in the K-ATP channel, replacing the amino acid glutamic acid with the amino acid lysine at position 23, written as Glu23Lys or E23K. People with type 2 diabetes have hyperglycemia because the body does not respond correctly to the insulin secreted from beta cells. The same variant has also been associated with changes in the heart's response to stress, leading to an increased risk of heart failure. Although changes in the KCNJ11 gene can be associated with type 2 diabetes and heart failure, a combination of lifestyle, genetic, and environmental factors all play a part in determining the risk of these complex disorders.
3. Other Names for This Gene
ATP-sensitive inward rectifier potassium channel 11
beta-cell inward rectifier subunit
inward rectifier K(+) channel Kir6.2
inwardly rectifying potassium channel KIR6.2
potassium channel, inwardly rectifying subfamily J member 11
potassium channel, inwardly rectifying subfamily J, member 11
potassium inwardly-rectifying channel, subfamily J, member 11
The entry is from https://medlineplus.gov/genetics/gene/kcnj11
- Bennett K, James C, Hussain K. Pancreatic β-cell KATP channels: Hypoglycaemia and hyperglycaemia. Rev Endocr Metab Disord. 2010 Sep;11(3):157-63. doi:10.1007/s11154-010-9144-2. Review.
- Flanagan SE, Clauin S, Bellanné-Chantelot C, de Lonlay P, Harries LW, GloynAL, Ellard S. Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) indiabetes mellitus and hyperinsulinism. Hum Mutat. 2009 Feb;30(2):170-80. doi:10.1002/humu.20838. Review.
- Flanagan SE, Edghill EL, Gloyn AL, Ellard S, Hattersley AT. Mutations inKCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in thefirst 6 months of life, with the phenotype determined by genotype. Diabetologia. 2006 Jun;49(6):1190-7.
- Gloyn AL, Siddiqui J, Ellard S. Mutations in the genes encoding the pancreaticbeta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetesmellitus and hyperinsulinism. Hum Mutat. 2006 Mar;27(3):220-31. Review.
- Gloyn AL, Weedon MN, Owen KR, Turner MJ, Knight BA, Hitman G, Walker M, LevyJC, Sampson M, Halford S, McCarthy MI, Hattersley AT, Frayling TM. Large-scaleassociation studies of variants in genes encoding the pancreatic beta-cell KATPchannel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23Kvariant is associated with type 2 diabetes. Diabetes. 2003 Feb;52(2):568-72.
- James C, Kapoor RR, Ismail D, Hussain K. The genetic basis of congenitalhyperinsulinism. J Med Genet. 2009 May;46(5):289-99. doi:10.1136/jmg.2008.064337.
- Polak M, Cavé H. Neonatal diabetes mellitus: a disease linked to multiplemechanisms. Orphanet J Rare Dis. 2007 Mar 9;2:12. Review.
- Reyes S, Park S, Johnson BD, Terzic A, Olson TM. KATP channel Kir6.2 E23Kvariant overrepresented in human heart failure is associated with impairedexercise stress response. Hum Genet. 2009 Dec;126(6):779-89. doi:10.1007/s00439-009-0731-9.
- Rubio-Cabezas O, Klupa T, Malecki MT; CEED3 Consortium. Permanent neonataldiabetes mellitus--the importance of diabetes differential diagnosis in neonates and infants. Eur J Clin Invest. 2011 Mar;41(3):323-33. doi:10.1111/j.1365-2362.2010.02409.x.