Kir6.2 Explained

K_ir6.2 is a major subunit of the ATP-sensitive K⁺ channel, a lipid-gated inward-rectifier potassium ion channel.^[1] The gene encoding the channel is called KCNJ11 and mutations in this gene are associated with congenital hyperinsulinism.^[2]

Structure

It is an integral membrane protein. The protein, which has a greater tendency to allow potassium to flow into a cell rather than out of a cell, is controlled by G-proteins and is found associated with the sulfonylurea receptor (SUR) to constitute the ATP-sensitive K⁺ channel.

Pathology

Mutations in this gene are a cause of congenital hyperinsulinism (CHI), an autosomal recessive disorder characterized by unregulated insulin secretion.^[3] Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM).^{[1] [4]}

See also

• Inward-rectifier potassium ion channel
• Potassium channel

Further reading

• Aguilar-Bryan L, Bryan J . Molecular biology of adenosine triphosphate-sensitive potassium channels . Endocrine Reviews . 20 . 2 . 101–135 . April 1999 . 10204114 . 10.1210/edrv.20.2.0361 . free .
• Meissner T, Beinbrech B, Mayatepek E . Congenital hyperinsulinism: molecular basis of a heterogeneous disease . Human Mutation . 13 . 5 . 351–361 . 1999 . 10338089 . 10.1002/(SICI)1098-1004(1999)13:5<351::AID-HUMU3>3.0.CO;2-R . 30125046 . free .
• Kubo Y, Adelman JP, Clapham DE, Jan LY, Karschin A, Kurachi Y, Lazdunski M, Nichols CG, Seino S, Vandenberg CA . 6 . International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels . Pharmacological Reviews . 57 . 4 . 509–526 . December 2005 . 16382105 . 10.1124/pr.57.4.11 . 11588492 .
• Gloyn AL, Siddiqui J, Ellard S . Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism . Human Mutation . 27 . 3 . 220–231 . March 2006 . 16416420 . 10.1002/humu.20292 . 38053792 . free .
• Flechtner I, de Lonlay P, Polak M . Diabetes and hypoglycaemia in young children and mutations in the Kir6.2 subunit of the potassium channel: therapeutic consequences . Diabetes & Metabolism . 32 . 6 . 569–580 . December 2006 . 17296510 . 10.1016/S1262-3636(07)70311-7 .
• Inagaki N, Gonoi T, Clement JP, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L, Seino S, Bryan J . 6 . Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor . Science . 270 . 5239 . 1166–1170 . November 1995 . 7502040 . 10.1126/science.270.5239.1166 . 1995Sci...270.1166I . 26409797 .
• Thomas PM, Cote GJ, Hallman DM, Mathew PM . Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy . American Journal of Human Genetics . 56 . 2 . 416–421 . February 1995 . 7847376 . 1801118 .
• Iwasaki N, Kawamura M, Yamagata K, Cox NJ, Karibe S, Ohgawara H, Inagaki N, Seino S, Bell GI, Omori Y . 6 . Identification of microsatellite markers near the human genes encoding the beta-cell ATP-sensitive K+ channel and linkage studies with NIDDM in Japanese . Diabetes . 45 . 2 . 267–269 . February 1996 . 8549873 . 10.2337/diabetes.45.2.267 .
• Sakura H, Wat N, Horton V, Millns H, Turner RC, Ashcroft FM . 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 . 39 . 10 . 1233–1236 . October 1996 . 8897013 . 10.1007/BF02658512 . 9490874 .
• Thomas P, Ye Y, Lightner E . Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy . Human Molecular Genetics . 5 . 11 . 1809–1812 . November 1996 . 8923010 . 10.1093/hmg/5.11.1809 . free .
• Inoue H, Ferrer J, Warren-Perry M, Zhang Y, Millns H, Turner RC, Elbein SC, Hampe CL, Suarez BK, Inagaki N, Seino S, Permutt MA . 6 . Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM . Diabetes . 46 . 3 . 502–507 . March 1997 . 9032109 . 10.2337/diabetes.46.3.502 .
• Tucker SJ, Gribble FM, Zhao C, Trapp S, Ashcroft FM . Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor . Nature . 387 . 6629 . 179–183 . May 1997 . 9144288 . 10.1038/387179a0 . 21570773 . 1997Natur.387..179T .
• Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A . 6 . Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis . Nature Genetics . 22 . 3 . 239–247 . July 1999 . 10391210 . 10.1038/10297 . 4636523 .
• Tucker SJ, Ashcroft FM . Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2 . The Journal of Biological Chemistry . 274 . 47 . 33393–33397 . November 1999 . 10559219 . 10.1074/jbc.274.47.33393 . free .
• Cui Y, Giblin JP, Clapp LH, Tinker A . A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits . Proceedings of the National Academy of Sciences of the United States of America . 98 . 2 . 729–734 . January 2001 . 11136227 . 14656 . 10.1073/pnas.011370498 . free .
• Giblin JP, Cui Y, Clapp LH, Tinker A . Assembly limits the pharmacological complexity of ATP-sensitive potassium channels . The Journal of Biological Chemistry . 277 . 16 . 13717–13723 . April 2002 . 11825905 . 10.1074/jbc.M112209200 . free .
• Crawford RM, Budas GR, Jovanović S, Ranki HJ, Wilson TJ, Davies AM, Jovanović A . M-LDH serves as a sarcolemmal K(ATP) channel subunit essential for cell protection against ischemia . The EMBO Journal . 21 . 15 . 3936–3948 . August 2002 . 12145195 . 126135 . 10.1093/emboj/cdf388 .
• Tschritter O, Stumvoll M, Machicao F, Holzwarth M, Weisser M, Maerker E, Teigeler A, Häring H, Fritsche A . 6 . The prevalent Glu23Lys polymorphism in the potassium inward rectifier 6.2 (KIR6.2) gene is associated with impaired glucagon suppression in response to hyperglycemia . Diabetes . 51 . 9 . 2854–2860 . September 2002 . 12196481 . 10.2337/diabetes.51.9.2854 . free .

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hyperinsulinism
• GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus

Notes and References

1. Web site: Entrez Gene: KCNJ11 potassium inwardly-rectifying channel, subfamily J, member 11.
2. Smith AJ, Taneja TK, Mankouri J, Sivaprasadarao A . Molecular cell biology of KATP channels: implications for neonatal diabetes . Expert Reviews in Molecular Medicine . 9 . 21 . 1–17 . August 2007 . 17666135 . 10.1017/S1462399407000403 . 24280714 .
3. Kapoor RR, Flanagan SE, Arya VB, Shield JP, Ellard S, Hussain K . Clinical and molecular characterisation of 300 patients with congenital hyperinsulinism . European Journal of Endocrinology . 168 . 4 . 557–564 . April 2013 . 23345197 . 3599069 . 10.1530/EJE-12-0673 .
4. Koo BK, Cho YM, Park BL, Cheong HS, Shin HD, Jang HC, Kim SY, Lee HK, Park KS . 6 . Polymorphisms of KCNJ11 (Kir6.2 gene) are associated with Type 2 diabetes and hypertension in the Korean population . Diabetic Medicine . 24 . 2 . 178–186 . February 2007 . 17257281 . 10.1111/j.1464-5491.2006.02050.x . 22127350 .