Kir6.2

KCNJ11
Identifiers
Aliases	KCNJ11, BIR, HHF2, IKATP, KIR6.2, MODY13, PHHI, TNDM3, potassium voltage-gated channel subfamily J member 11, potassium inwardly rectifying channel subfamily J member 11, PNDM2
External IDs	OMIM: 600937; MGI: 107501; HomoloGene: 441; GeneCards: KCNJ11; OMA:KCNJ11 - orthologs
Gene location (Human) Chr. Chromosome 11 (human) Band 11p15.1 Start 17,365,172 bp End 17,389,331 bp
Gene location (Mouse) Chr. Chromosome 7 (mouse) Band 7 B3|7 29.66 cM Start 45,743,377 bp End 45,750,188 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle muscle of thigh tibialis anterior muscle right hemisphere of cerebellum apex of heart islet of Langerhans right frontal lobe prefrontal cortex left ventricle skeletal muscle tissue Top expressed in gastrula muscle of thigh medial ganglionic eminence molar calvaria triceps brachii muscle temporal muscle ankle intercostal muscle major salivary gland More reference expression data BioGPS n/a
Gene ontology Molecular function transmembrane transporter binding potassium ion binding voltage-gated ion channel activity ankyrin binding voltage-gated potassium channel activity ATP-activated inward rectifier potassium channel activity inward rectifier potassium channel activity ATP binding protein binding protein C-terminus binding heat shock protein binding Cellular component integral component of membrane cytosol endosome nuclear envelope membrane intracellular membrane-bounded organelle intercalated disc cell body fiber T-tubule myelin sheath plasma membrane integral component of plasma membrane soma endoplasmic reticulum mitochondrion axolemma inward rectifying potassium channel sarcolemma acrosomal vesicle Biological process positive regulation of cation channel activity response to ATP response to estradiol negative regulation of insulin secretion regulation of insulin secretion response to testosterone regulation of membrane potential cellular response to tumor necrosis factor regulation of ion transmembrane transport nervous system process cellular response to nicotine ion transport potassium ion transport response to ischemia potassium ion transmembrane transport glucose metabolic process cellular response to glucose stimulus positive regulation of protein localization to plasma membrane potassium ion import across plasma membrane transmembrane transport regulation of cardiac conduction Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3767 16514 Ensembl ENSG00000187486 ENSMUSG00000096146 UniProt Q14654 Q61743 RefSeq (mRNA) NM_000525 NM_001166290 NM_001377296 NM_001377297 NM_001204411 NM_010602 RefSeq (protein) NP_000516 NP_001159762 NP_001364225 NP_001364226 NP_001191340 NP_034732 Location (UCSC) Chr 11: 17.37 – 17.39 Mb Chr 7: 45.74 – 45.75 Mb PubMed search
Wikidata
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K_ir6.2 is a major subunit of the ATP-sensitive K⁺ channel, a lipid-gated inward-rectifier potassium ion channel. The gene encoding the channel is called KCNJ11 and mutations in this gene are associated with congenital hyperinsulinism.

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 familial persistent hyperinsulinemic hypoglycemia of infancy (PHHI), an autosomal recessive disorder characterized by unregulated insulin secretion. Defects in this gene may also contribute to autosomal dominant non-insulin-dependent diabetes mellitus type II (NIDDM).

See also

• Inward-rectifier potassium ion channel
• Potassium channel

Further reading

• Aguilar-Bryan L, Bryan J (1999). "Molecular biology of adenosine triphosphate-sensitive potassium channels". Endocr. Rev. 20 (2): 101–35. doi:10.1210/er.20.2.101. PMID 10204114.
• Meissner T, Beinbrech B, Mayatepek E (1999). "Congenital hyperinsulinism: molecular basis of a heterogeneous disease". Hum. Mutat. 13 (5): 351–61. doi:10.1002/(SICI)1098-1004(1999)13:5<351::AID-HUMU3>3.0.CO;2-R. PMID 10338089.
• Kubo Y, Adelman JP, Clapham DE, et al. (2006). "International Union of Pharmacology. LIV. Nomenclature and molecular relationships of inwardly rectifying potassium channels". Pharmacol. Rev. 57 (4): 509–26. doi:10.1124/pr.57.4.11. PMID 16382105.
• Gloyn AL, Siddiqui J, Ellard S (2006). "Mutations in the genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) in diabetes mellitus and hyperinsulinism". Hum. Mutat. 27 (3): 220–31. doi:10.1002/humu.20292. PMID 16416420.
• Flechtner I, de Lonlay P, Polak M (2007). "Diabetes and hypoglycaemia in young children and mutations in the Kir6.2 subunit of the potassium channel: therapeutic consequences". Diabetes Metab. 32 (6): 569–80. doi:10.1016/S1262-3636(07)70311-7. PMID 17296510.
• Inagaki N, Gonoi T, Clement JP, et al. (1996). "Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor". Science. 270 (5239): 1166–1170. doi:10.1126/science.270.5239.1166. PMID 7502040.
• Thomas PM, Cote GJ, Hallman DM, Mathew PM (1995). "Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy". Am. J. Hum. Genet. 56 (2): 416–21. PMC 1801118. PMID 7847376.
• Iwasaki N, Kawamura M, Yamagata K, et al. (1996). "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): 267–9. doi:10.2337/diabetes.45.2.267. PMID 8549873.
• Sakura H, Wat N, Horton V, et al. (1997). "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. doi:10.1007/BF02658512. PMID 8897013.
• Thomas P, Ye Y, Lightner E (1997). "Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy". Hum. Mol. Genet. 5 (11): 1809–1812. doi:10.1093/hmg/5.11.1809. PMID 8923010.
• Inoue H, Ferrer J, Warren-Perry M, et al. (1997). "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): 502–7. doi:10.2337/diabetes.46.3.502. PMID 9032109.
• Tucker SJ, Gribble FM, Zhao C, et al. (1997). "Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor". Nature. 387 (6629): 179–83. doi:10.1038/387179a0. PMID 9144288.
• Halushka MK, Fan JB, Bentley K, et al. (1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nat. Genet. 22 (3): 239–47. doi:10.1038/10297. PMID 10391210.
• Tucker SJ, Ashcroft FM (1999). "Mapping of the physical interaction between the intracellular domains of an inwardly rectifying potassium channel, Kir6.2". J. Biol. Chem. 274 (47): 33393–7. doi:10.1074/jbc.274.47.33393. PMID 10559219.
• Cui Y, Giblin JP, Clapp LH, Tinker A (2001). "A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits". Proc. Natl. Acad. Sci. U.S.A. 98 (2): 729–34. doi:10.1073/pnas.011370498. PMC 14656. PMID 11136227.
• Giblin JP, Cui Y, Clapp LH, Tinker A (2002). "Assembly limits the pharmacological complexity of ATP-sensitive potassium channels". J. Biol. Chem. 277 (16): 13717–23. doi:10.1074/jbc.M112209200. PMID 11825905.
• Crawford RM, Budas GR, Jovanović S, et al. (2002). "M-LDH serves as a sarcolemmal K(ATP) channel subunit essential for cell protection against ischemia". EMBO J. 21 (15): 3936–3948. doi:10.1093/emboj/cdf388. PMC 126135. PMID 12145195.
• Tschritter O, Stumvoll M, Machicao F, et al. (2002). "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. doi:10.2337/diabetes.51.9.2854. PMID 12196481.

External links

• GeneReviews/NCBI/NIH/UW entry on Familial Hyperinsulinism
• GeneReviews/NCBI/NIH/UW entry on Permanent Neonatal Diabetes Mellitus
• KCNJ11+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
• SUR1+protein,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.