KCJ11_HUMAN
ID KCJ11_HUMAN Reviewed; 390 AA.
AC Q14654; B4DWI4; E9PNK0; Q2M1H7; Q58EX3; Q8IW96;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 25-MAY-2022, sequence version 3.
DT 03-AUG-2022, entry version 219.
DE RecName: Full=ATP-sensitive inward rectifier potassium channel 11;
DE AltName: Full=IKATP;
DE AltName: Full=Inward rectifier K(+) channel Kir6.2;
DE AltName: Full=Potassium channel, inwardly rectifying subfamily J member 11;
GN Name=KCNJ11;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLU-23; SER-148 AND
RP ILE-337.
RC TISSUE=Placenta;
RX PubMed=7502040; DOI=10.1126/science.270.5239.1166;
RA Inagaki N., Gonoi T., Clement J.P. IV, Namba N., Inazawa J., Gonzalez G.,
RA Aguilar-Bryan L., Seino S., Bryan J.;
RT "Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea
RT receptor.";
RL Science 270:1166-1170(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ILE-337.
RC TISSUE=Mammary gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP GLU-23 AND ILE-337.
RC TISSUE=Ovary, and Spleen;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, AND INTERACTION WITH ABCC9.
RX PubMed=9831708; DOI=10.1161/01.res.83.11.1132;
RA Babenko A.P., Gonzalez G., Aguilar-Bryan L., Bryan J.;
RT "Reconstituted human cardiac KATP channels: functional identity with the
RT native channels from the sarcolemma of human ventricular cells.";
RL Circ. Res. 83:1132-1143(1998).
RN [6]
RP MOLECULAR BASIS OF ATP SENSITIVITY.
RX PubMed=12524280; DOI=10.1016/s0006-3495(03)74847-4;
RA Ribalet B., John S.A., Weiss J.N.;
RT "Molecular basis for Kir6.2 channel inhibition by adenine nucleotides.";
RL Biophys. J. 84:266-276(2003).
RN [7]
RP INVOLVEMENT IN PNDM2, VARIANT PNDM2 LEU-167, AND CHARACTERIZATION OF
RP VARIANT PNDM2 LEU-167.
RX PubMed=17652641; DOI=10.1212/01.wnl.0000268488.51776.53;
RA Shimomura K., Horster F., de Wet H., Flanagan S.E., Ellard S.,
RA Hattersley A.T., Wolf N.I., Ashcroft F., Ebinger F.;
RT "A novel mutation causing DEND syndrome: a treatable channelopathy of
RT pancreas and brain.";
RL Neurology 69:1342-1349(2007).
RN [8]
RP INVOLVEMENT IN HHF2, AND VARIANTS HHF2 LEU-55; ARG-156 AND GLU-204.
RX PubMed=18596924; DOI=10.1172/jci35414;
RA Pinney S.E., MacMullen C., Becker S., Lin Y.W., Hanna C., Thornton P.,
RA Ganguly A., Shyng S.L., Stanley C.A.;
RT "Clinical characteristics and biochemical mechanisms of congenital
RT hyperinsulinism associated with dominant KATP channel mutations.";
RL J. Clin. Invest. 118:2877-2886(2008).
RN [9]
RP INVOLVEMENT IN HHF2, VARIANT HHF2 LYS-282, AND CHARACTERIZATION OF VARIANT
RP HHF2 LYS-282.
RX PubMed=19357197; DOI=10.1093/hmg/ddp179;
RA Taneja T.K., Mankouri J., Karnik R., Kannan S., Smith A.J., Munsey T.,
RA Christesen H.B., Beech D.J., Sivaprasadarao A.;
RT "Sar1-GTPase-dependent ER exit of KATP channels revealed by a mutation
RT causing congenital hyperinsulinism.";
RL Hum. Mol. Genet. 18:2400-2413(2009).
RN [10]
RP INVOLVEMENT IN PNDM2, VARIANTS PNDM2 TYR-60 AND LEU-64, AND
RP CHARACTERIZATION OF VARIANTS PNDM2 TYR-60 AND LEU-64.
RX PubMed=20022885; DOI=10.1093/hmg/ddp554;
RA Maennikkoe R., Jefferies C., Flanagan S.E., Hattersley A., Ellard S.,
RA Ashcroft F.M.;
RT "Interaction between mutations in the slide helix of Kir6.2 associated with
RT neonatal diabetes and neurological symptoms.";
RL Hum. Mol. Genet. 19:963-972(2010).
RN [11]
RP REVIEW ON VARIANTS.
RX PubMed=10338089;
RX DOI=10.1002/(sici)1098-1004(1999)13:5<351::aid-humu3>3.0.co;2-r;
RA Meissner T., Beinbrech B., Mayatepek E.;
RT "Congenital hyperinsulinism: molecular basis of a heterogeneous disease.";
RL Hum. Mutat. 13:351-361(1999).
RN [12]
RP FUNCTION, CHARACTERIZATION OF VARIANT PNDM2 ILE-333, AND INTERACTION WITH
RP ABCC9.
RX PubMed=17855752; DOI=10.1113/jphysiol.2007.143149;
RA Tammaro P., Ashcroft F.M.;
RT "A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP
RT channel alters coupling with the SUR2A subunit.";
RL J. Physiol. (Lond.) 584:743-753(2007).
RN [13]
RP PHOSPHORYLATION AT THR-341 AND SER-385.
RX PubMed=18280666; DOI=10.1016/j.neuroscience.2008.01.003;
RA Lin Y.F., Chai Y.;
RT "Functional modulation of the ATP-sensitive potassium channel by
RT extracellular signal-regulated kinase-mediated phosphorylation.";
RL Neuroscience 152:371-380(2008).
RN [14]
RP INVOLVEMENT IN MODY13, AND VARIANT MODY13 LYS-227.
RX PubMed=22701567; DOI=10.1371/journal.pone.0037423;
RA Bonnefond A., Philippe J., Durand E., Dechaume A., Huyvaert M.,
RA Montagne L., Marre M., Balkau B., Fajardy I., Vambergue A., Vatin V.,
RA Delplanque J., Le Guilcher D., De Graeve F., Lecoeur C., Sand O.,
RA Vaxillaire M., Froguel P.;
RT "Whole-exome sequencing and high throughput genotyping identified KCNJ11 as
RT the thirteenth MODY gene.";
RL PLoS ONE 7:E37423-E37423(2012).
RN [15]
RP FUNCTION, CHARACTERIZATION OF VARIANT PNDM2 LEU-64, AND MUTAGENESIS OF
RP VAL-64.
RX PubMed=28842488; DOI=10.1074/jbc.m117.804971;
RA Cooper P.E., McClenaghan C., Chen X., Stary-Weinzinger A., Nichols C.G.;
RT "Conserved functional consequences of disease-associated mutations in the
RT slide-helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive potassium
RT channel.";
RL J. Biol. Chem. 292:17387-17398(2017).
RN [16]
RP VARIANT HHF2 PRO-147.
RX PubMed=7847376;
RA Thomas P.M., Cote G.J., Hallman D.M., Mathew P.M.;
RT "Homozygosity mapping, to chromosome 11p, of the gene for familial
RT persistent hyperinsulinemic hypoglycemia of infancy.";
RL Am. J. Hum. Genet. 56:416-421(1995).
RN [17]
RP VARIANT HHF2 PRO-147.
RX PubMed=8923010; DOI=10.1093/hmg/5.11.1809;
RA Thomas P., Ye Y., Lightner E.;
RT "Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to
RT familial persistent hyperinsulinemic hypoglycemia of infancy.";
RL Hum. Mol. Genet. 5:1809-1812(1996).
RN [18]
RP VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, AND VARIANTS GLU-23; VAL-270;
RP ILE-337 AND CYS-385.
RX PubMed=8897013; DOI=10.1007/bf02658512;
RA Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M.;
RT "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell
RT ATP-sensitive K-channel: no association with NIDDM in white Caucasian
RT subjects or evidence of abnormal function when expressed in vitro.";
RL Diabetologia 39:1233-1236(1996).
RN [19]
RP VARIANTS LYS-10; GLU-23; VAL-270 AND ILE-337.
RX PubMed=9032109; DOI=10.2337/diab.46.3.502;
RA Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C.,
RA Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A.;
RT "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+
RT channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian
RT patients with NIDDM.";
RL Diabetes 46:502-507(1997).
RN [20]
RP VARIANT HHF2 ARG-91.
RX PubMed=10204114; DOI=10.1210/edrv.20.2.0361;
RA Aguilar-Bryan L., Bryan J.;
RT "Molecular biology of adenosine triphosphate-sensitive potassium
RT channels.";
RL Endocr. Rev. 20:101-135(1999).
RN [21]
RP VARIANTS GLU-23 AND ILE-337.
RX PubMed=10391210; DOI=10.1038/10297;
RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A.,
RA Cooper R., Lipshutz R., Chakravarti A.;
RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood-
RT pressure homeostasis.";
RL Nat. Genet. 22:239-247(1999).
RN [22]
RP VARIANT HHF2 ASN-67.
RX PubMed=12364426; DOI=10.1210/jc.2002-020378;
RA Huopio H., Jaeaeskelaeinen J., Komulainen J., Miettinen R.,
RA Kaerkkaeinen P., Laakso M., Tapanainen P., Voutilainen R., Otonkoski T.;
RT "Acute insulin response tests for the differential diagnosis of congenital
RT hyperinsulinism.";
RL J. Clin. Endocrinol. Metab. 87:4502-4507(2002).
RN [23]
RP VARIANTS PNDM2 VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.
RX PubMed=15448106; DOI=10.2337/diabetes.53.10.2713;
RA Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H.,
RA Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L.,
RA Hattersley A.T., Molven A., Soevik O., Njoelstad P.R.;
RT "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2:
RT patient characteristics and initial response to sulfonylurea therapy.";
RL Diabetes 53:2713-2718(2004).
RN [24]
RP VARIANTS PNDM2 LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.
RX PubMed=15448107; DOI=10.2337/diabetes.53.10.2719;
RA Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L.,
RA Hattersley A.T., Czernichow P., Froguel P., Polak M.;
RT "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a
RT large cohort of French patients.";
RL Diabetes 53:2719-2722(2004).
RN [25]
RP VARIANT PNDM2 CYS-201.
RX PubMed=15292329; DOI=10.1210/jc.2004-0568;
RA Gloyn A.L., Cummings E.A., Edghill E.L., Harries L.W., Scott R., Costa T.,
RA Temple I.K., Hattersley A.T., Ellard S.;
RT "Permanent neonatal diabetes due to paternal germline mosaicism for an
RT activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the
RT beta-cell potassium adenosine triphosphate channel.";
RL J. Clin. Endocrinol. Metab. 89:3932-3935(2004).
RN [26]
RP VARIANT HHF2 LEU-254, AND CHARACTERIZATION OF VARIANT HHF2 LEU-254.
RX PubMed=15579781; DOI=10.1210/jc.2004-1233;
RA Tornovsky S., Crane A., Cosgrove K.E., Hussain K., Lavie J., Heyman M.,
RA Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O., Nahari E., Potikha T.,
RA Zangen D., Tenenbaum-Rakover Y., de Vries L., Argente J., Gracia R.,
RA Landau H., Eliakim A., Lindley K., Dunne M.J., Aguilar-Bryan L., Glaser B.;
RT "Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence
RT for additional locus heterogeneity.";
RL J. Clin. Endocrinol. Metab. 89:6224-6234(2004).
RN [27]
RP VARIANTS PNDM2 ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, AND
RP CHARACTERIZATION OF VARIANT PNDM2 HIS-201.
RX PubMed=15115830; DOI=10.1056/nejmoa032922;
RA Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J.,
RA Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J.,
RA Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H.,
RA Sumnik Z., van Rhijn A., Wales J.K.H., Clark P., Gorman S., Aisenberg J.,
RA Ellard S., Njoelstad P.R., Ashcroft F.M., Hattersley A.T.;
RT "Activating mutations in the gene encoding the ATP-sensitive potassium-
RT channel subunit Kir6.2 and permanent neonatal diabetes.";
RL N. Engl. J. Med. 350:1838-1849(2004).
RN [28]
RP ERRATUM OF PUBMED:15115830.
RA Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J.,
RA Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J.,
RA Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H.,
RA Sumnik Z., van Rhijn A., Wales J.K.H., Clark P., Gorman S., Aisenberg J.,
RA Ellard S., Njoelstad P.R., Ashcroft F.M., Hattersley A.T.;
RL N. Engl. J. Med. 351:1470-1470(2004).
RN [29]
RP CHARACTERIZATION OF VARIANTS PNDM2 ARG-52; GLY-59 AND CYS-201.
RX PubMed=15583126; DOI=10.1073/pnas.0404756101;
RA Proks P., Antcliff J.F., Lippiat J., Gloyn A.L., Hattersley A.T.,
RA Ashcroft F.M.;
RT "Molecular basis of Kir6.2 mutations associated with neonatal diabetes or
RT neonatal diabetes plus neurological features.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:17539-17544(2004).
RN [30]
RP VARIANT HHF2 HIS-34, AND VARIANTS GLU-23; SER-148 AND ILE-337.
RX PubMed=15807877; DOI=10.1111/j.1365-2265.2005.02242.x;
RA Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N.,
RA Fujinaga H., Tsumura K., Kikuchi K., Ono J.;
RT "Genotypes of the pancreatic beta-cell K-ATP channel and clinical
RT phenotypes of Japanese patients with persistent hyperinsulinaemic
RT hypoglycaemia of infancy.";
RL Clin. Endocrinol. (Oxf.) 62:458-465(2005).
RN [31]
RP VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, AND CHARACTERIZATION OF VARIANTS
RP TNDM3 SER-53; ARG-53 AND VAL-182.
RX PubMed=15718250; DOI=10.1093/hmg/ddi086;
RA Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R.,
RA Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K.,
RA Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T.;
RT "Relapsing diabetes can result from moderately activating mutations in
RT KCNJ11.";
RL Hum. Mol. Genet. 14:925-934(2005).
RN [32]
RP VARIANTS PNDM2 PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.
RX PubMed=15580558; DOI=10.1002/humu.20124;
RG The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes;
RA Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B.,
RA Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G.,
RA Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F.;
RT "KCNJ11 activating mutations in Italian patients with permanent neonatal
RT diabetes.";
RL Hum. Mutat. 25:22-27(2005).
RN [33]
RP VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.
RX PubMed=15562009; DOI=10.1210/jc.2004-1604;
RA Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S.,
RA Stanley C.A.;
RT "Genotype-phenotype correlations in children with congenital
RT hyperinsulinism due to recessive mutations of the adenosine triphosphate-
RT sensitive potassium channel genes.";
RL J. Clin. Endocrinol. Metab. 90:789-794(2005).
RN [34]
RP VARIANT TNDM3 ARG-42, AND CHARACTERIZATION OF VARIANT TNDM3 ARG-42.
RX PubMed=15784703; DOI=10.1210/jc.2005-0096;
RA Yorifuji T., Nagashima K., Kurokawa K., Kawai M., Oishi M., Akazawa Y.,
RA Hosokawa M., Yamada Y., Inagaki N., Nakahata T.;
RT "The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient
RT neonatal diabetes, childhood diabetes, or later-onset, apparently type 2
RT diabetes mellitus.";
RL J. Clin. Endocrinol. Metab. 90:3174-3178(2005).
RN [35]
RP VARIANT HHF2 ARG-259, AND CHARACTERIZATION OF VARIANT HHF2 ARG-259.
RX PubMed=15998776; DOI=10.1210/jc.2005-0202;
RA Marthinet E., Bloc A., Oka Y., Tanizawa Y., Wehrle-Haller B., Bancila V.,
RA Dubuis J.-M., Philippe J., Schwitzgebel V.M.;
RT "Severe congenital hyperinsulinism caused by a mutation in the Kir6.2
RT subunit of the adenosine triphosphate-sensitive potassium channel impairing
RT trafficking and function.";
RL J. Clin. Endocrinol. Metab. 90:5401-5406(2005).
RN [36]
RP VARIANTS PNDM2 GLN-50 AND PRO-50, AND CHARACTERIZATION OF VARIANTS PNDM2
RP GLN-50 AND PRO-50.
RX PubMed=16731833; DOI=10.2337/db05-1640;
RA Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F.,
RA Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M.;
RT "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal
RT diabetes produce different functional effects.";
RL Diabetes 55:1705-1712(2006).
RN [37]
RP VARIANTS PNDM2 TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164;
RP TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.
RX PubMed=16609879; DOI=10.1007/s00125-006-0246-z;
RA Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T.;
RT "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes
RT diagnosed in the first 6 months of life, with the phenotype determined by
RT genotype.";
RL Diabetologia 49:1190-1197(2006).
RN [38]
RP VARIANTS GLU-23 AND ILE-337.
RX PubMed=16429405; DOI=10.1002/humu.9401;
RA Fernandez-Marmiesse A., Salas A., Vega A., Fernandez-Lorenzo J.R.,
RA Barreiro J., Carracedo A.;
RT "Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of
RT Infancy (HI).";
RL Hum. Mutat. 27:214-214(2006).
RN [39]
RP VARIANT HHF2 LEU-55, AND CHARACTERIZATION OF VARIANT HHF2 LEU-55.
RX PubMed=16332676; DOI=10.1074/jbc.m511875200;
RA Lin Y.-W., MacMullen C., Ganguly A., Stanley C.A., Shyng S.-L.;
RT "A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces
RT the intrinsic open probability of beta-cell ATP-sensitive potassium
RT channels.";
RL J. Biol. Chem. 281:3006-3012(2006).
RN [40]
RP VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.
RX PubMed=16357843; DOI=10.1038/modpathol.3800497;
RA Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A.,
RA Ruchelli E.D., Stanley C.A.;
RT "Molecular and immunohistochemical analyses of the focal form of congenital
RT hyperinsulinism.";
RL Mod. Pathol. 19:122-129(2006).
RN [41]
RP VARIANTS PNDM2 TYR-46; PRO-164 AND HIS-201.
RX PubMed=17213273; DOI=10.1210/jc.2006-2490;
RA Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E.,
RA Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E.,
RA Hattersley A.T., Ellard S., Klimes I.;
RT "Prevalence of permanent neonatal diabetes in Slovakia and successful
RT replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8
RT mutation carriers.";
RL J. Clin. Endocrinol. Metab. 92:1276-1282(2007).
CC -!- FUNCTION: This receptor is controlled by G proteins. Inward rectifier
CC potassium channels are characterized by a greater tendency to allow
CC potassium to flow into the cell rather than out of it. Their voltage
CC dependence is regulated by the concentration of extracellular
CC potassium; as external potassium is raised, the voltage range of the
CC channel opening shifts to more positive voltages. The inward
CC rectification is mainly due to the blockage of outward current by
CC internal magnesium. Can be blocked by extracellular barium (By
CC similarity). Subunit of ATP-sensitive potassium channels (KATP). Can
CC form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11
CC forms the channel pore while ABCC9 is required for activation and
CC regulation. {ECO:0000250, ECO:0000269|PubMed:17855752,
CC ECO:0000269|PubMed:28842488, ECO:0000269|PubMed:9831708}.
CC -!- SUBUNIT: Interacts with ABCC8/SUR. Interacts with ABCC9/SUR2.
CC {ECO:0000269|PubMed:17855752, ECO:0000269|PubMed:9831708}.
CC -!- INTERACTION:
CC Q14654; Q09428-1: ABCC8; NbExp=2; IntAct=EBI-2866553, EBI-15807650;
CC Q14654; Q01484: ANK2; NbExp=6; IntAct=EBI-2866553, EBI-941975;
CC Q14654; Q96B26: EXOSC8; NbExp=3; IntAct=EBI-2866553, EBI-371922;
CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q14654-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q14654-2; Sequence=VSP_045270;
CC -!- PTM: Phosphorylation by MAPK1 results in changes in channel gating that
CC destabilize the closed states and reduce the ATP sensitivity.
CC {ECO:0000269|PubMed:18280666}.
CC -!- DISEASE: Familial hyperinsulinemic hypoglycemia 2 (HHF2) [MIM:601820]:
CC Most common cause of persistent hypoglycemia in infancy. Unless early
CC and aggressive intervention is undertaken, brain damage from recurrent
CC episodes of hypoglycemia may occur. {ECO:0000269|PubMed:10204114,
CC ECO:0000269|PubMed:12364426, ECO:0000269|PubMed:15562009,
CC ECO:0000269|PubMed:15579781, ECO:0000269|PubMed:15807877,
CC ECO:0000269|PubMed:15998776, ECO:0000269|PubMed:16332676,
CC ECO:0000269|PubMed:16357843, ECO:0000269|PubMed:18596924,
CC ECO:0000269|PubMed:19357197, ECO:0000269|PubMed:7847376,
CC ECO:0000269|PubMed:8923010}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Diabetes mellitus, permanent neonatal, 2 (PNDM2) [MIM:618856]:
CC A form of permanent neonatal diabetes mellitus, a type of diabetes
CC characterized by onset of persistent hyperglycemia within the first six
CC months of life. Initial clinical manifestations include intrauterine
CC growth retardation, hyperglycemia, glycosuria, osmotic polyuria, severe
CC dehydration, and failure to thrive. Some PNDM2 patients may also have
CC developmental delay, muscle weakness, epilepsy and dysmorphic features.
CC PNDM2 transmission pattern is consistent with autosomal dominant
CC inheritance. {ECO:0000269|PubMed:15115830, ECO:0000269|PubMed:15292329,
CC ECO:0000269|PubMed:15448106, ECO:0000269|PubMed:15448107,
CC ECO:0000269|PubMed:15580558, ECO:0000269|PubMed:15583126,
CC ECO:0000269|PubMed:16609879, ECO:0000269|PubMed:16731833,
CC ECO:0000269|PubMed:17213273, ECO:0000269|PubMed:17652641,
CC ECO:0000269|PubMed:17855752, ECO:0000269|PubMed:20022885,
CC ECO:0000269|PubMed:28842488}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Transient neonatal diabetes mellitus 3 (TNDM3) [MIM:610582]:
CC Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia
CC within the first month of life, is a rare entity. In about half of the
CC neonates, diabetes is transient and resolves at a median age of 3
CC months, whereas the rest have a permanent form of diabetes. In a
CC significant number of patients with transient neonatal diabetes
CC mellitus, diabetes type 2 appears later in life. The onset and severity
CC of TNDM3 is variable with childhood-onset diabetes, gestational
CC diabetes or adult-onset diabetes described.
CC {ECO:0000269|PubMed:15718250, ECO:0000269|PubMed:15784703}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Note=Defects in KCNJ11 may contribute to non-insulin-dependent
CC diabetes mellitus (NIDDM), also known as diabetes mellitus type 2.
CC -!- DISEASE: Maturity-onset diabetes of the young 13 (MODY13) [MIM:616329]:
CC A form of diabetes that is characterized by an autosomal dominant mode
CC of inheritance, onset in childhood or early adulthood (usually before
CC 25 years of age), a primary defect in insulin secretion and frequent
CC insulin-independence at the beginning of the disease.
CC {ECO:0000269|PubMed:22701567}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel (TC
CC 1.A.2.1) family. KCNJ11 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH40617.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; D50582; BAA09131.1; -; Genomic_DNA.
DR EMBL; AK301550; BAG63046.1; -; mRNA.
DR EMBL; AC124798; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC064497; AAH64497.1; -; mRNA.
DR EMBL; BC040617; AAH40617.1; ALT_INIT; mRNA.
DR EMBL; BC112358; AAI12359.1; -; mRNA.
DR CCDS; CCDS31436.1; -. [Q14654-1]
DR CCDS; CCDS53606.1; -. [Q14654-2]
DR PIR; A57616; A57616.
DR RefSeq; NP_001159762.1; NM_001166290.1.
DR PDB; 6C3O; EM; 3.90 A; A/B/C/D=1-390.
DR PDB; 6C3P; EM; 5.60 A; A/B/C/D=1-390.
DR PDBsum; 6C3O; -.
DR PDBsum; 6C3P; -.
DR AlphaFoldDB; Q14654; -.
DR SMR; Q14654; -.
DR BioGRID; 109969; 25.
DR ComplexPortal; CPX-195; Inward rectifying potassium channel complex, Kir6.2-SUR1.
DR ComplexPortal; CPX-197; Inward rectifying potassium channel complex, Kir6.2-SUR2A.
DR ComplexPortal; CPX-199; Inward rectifying potassium channel complex, Kir6.2-SUR2B.
DR CORUM; Q14654; -.
DR DIP; DIP-58643N; -.
DR ELM; Q14654; -.
DR IntAct; Q14654; 14.
DR STRING; 9606.ENSP00000345708; -.
DR BindingDB; Q14654; -.
DR ChEMBL; CHEMBL1886; -.
DR DrugBank; DB11148; Butamben.
DR DrugBank; DB01119; Diazoxide.
DR DrugBank; DB00222; Glimepiride.
DR DrugBank; DB01016; Glyburide.
DR DrugBank; DB00308; Ibutilide.
DR DrugBank; DB11633; Isavuconazole.
DR DrugBank; DB00922; Levosimendan.
DR DrugBank; DB01154; Thiamylal.
DR DrugBank; DB00839; Tolazamide.
DR DrugBank; DB00661; Verapamil.
DR DrugBank; DB01392; Yohimbine.
DR DrugCentral; Q14654; -.
DR TCDB; 1.A.2.1.17; the inward rectifier k(+) channel (irk-c) family.
DR iPTMnet; Q14654; -.
DR PhosphoSitePlus; Q14654; -.
DR SwissPalm; Q14654; -.
DR BioMuta; KCNJ11; -.
DR DMDM; 76803775; -.
DR MassIVE; Q14654; -.
DR PaxDb; Q14654; -.
DR PeptideAtlas; Q14654; -.
DR PRIDE; Q14654; -.
DR ProteomicsDB; 22438; -.
DR ProteomicsDB; 60093; -. [Q14654-1]
DR Antibodypedia; 24845; 465 antibodies from 37 providers.
DR DNASU; 3767; -.
DR Ensembl; ENST00000339994.5; ENSP00000345708.4; ENSG00000187486.7. [Q14654-1]
DR Ensembl; ENST00000528731.1; ENSP00000434755.1; ENSG00000187486.7. [Q14654-2]
DR Ensembl; ENST00000682350.1; ENSP00000508090.1; ENSG00000187486.7. [Q14654-2]
DR Ensembl; ENST00000682764.1; ENSP00000506780.1; ENSG00000187486.7. [Q14654-2]
DR GeneID; 3767; -.
DR KEGG; hsa:3767; -.
DR MANE-Select; ENST00000339994.5; ENSP00000345708.4; NM_000525.4; NP_000516.3.
DR UCSC; uc001mna.4; human. [Q14654-1]
DR CTD; 3767; -.
DR DisGeNET; 3767; -.
DR GeneCards; KCNJ11; -.
DR GeneReviews; KCNJ11; -.
DR HGNC; HGNC:6257; KCNJ11.
DR HPA; ENSG00000187486; Group enriched (skeletal muscle, tongue).
DR MalaCards; KCNJ11; -.
DR MIM; 600937; gene.
DR MIM; 601820; phenotype.
DR MIM; 610582; phenotype.
DR MIM; 616329; phenotype.
DR MIM; 618856; phenotype.
DR neXtProt; NX_Q14654; -.
DR OpenTargets; ENSG00000187486; -.
DR Orphanet; 276580; Autosomal dominant hyperinsulinism due to Kir6.2 deficiency.
DR Orphanet; 79644; Autosomal recessive hyperinsulinism due to Kir6.2 deficiency.
DR Orphanet; 79134; DEND syndrome.
DR Orphanet; 276603; Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency.
DR Orphanet; 99989; Intermediate DEND syndrome.
DR Orphanet; 99885; Isolated permanent neonatal diabetes mellitus.
DR Orphanet; 552; MODY.
DR Orphanet; 99886; Transient neonatal diabetes mellitus.
DR PharmGKB; PA217; -.
DR VEuPathDB; HostDB:ENSG00000187486; -.
DR eggNOG; KOG3827; Eukaryota.
DR GeneTree; ENSGT00990000203615; -.
DR HOGENOM; CLU_022738_4_0_1; -.
DR InParanoid; Q14654; -.
DR PhylomeDB; Q14654; -.
DR TreeFam; TF313676; -.
DR PathwayCommons; Q14654; -.
DR Reactome; R-HSA-1296025; ATP sensitive Potassium channels.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-422356; Regulation of insulin secretion.
DR Reactome; R-HSA-5578775; Ion homeostasis.
DR Reactome; R-HSA-5678420; Defective ABCC9 causes CMD10, ATFB12 and Cantu syndrome.
DR Reactome; R-HSA-5683177; Defective ABCC8 can cause hypo- and hyper-glycemias.
DR SignaLink; Q14654; -.
DR SIGNOR; Q14654; -.
DR BioGRID-ORCS; 3767; 19 hits in 1084 CRISPR screens.
DR ChiTaRS; KCNJ11; human.
DR GeneWiki; Kir6.2; -.
DR GenomeRNAi; 3767; -.
DR Pharos; Q14654; Tclin.
DR PRO; PR:Q14654; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q14654; protein.
DR Bgee; ENSG00000187486; Expressed in gastrocnemius and 96 other tissues.
DR ExpressionAtlas; Q14654; baseline and differential.
DR Genevisible; Q14654; HS.
DR GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR GO; GO:0008282; C:inward rectifying potassium channel; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:BHF-UCL.
DR GO; GO:0030315; C:T-tubule; ISS:BHF-UCL.
DR GO; GO:0030506; F:ankyrin binding; IPI:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; ISS:BHF-UCL.
DR GO; GO:0015272; F:ATP-activated inward rectifier potassium channel activity; ISS:BHF-UCL.
DR GO; GO:0019829; F:ATPase-coupled cation transmembrane transporter activity; ISS:ARUK-UCL.
DR GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR GO; GO:0030955; F:potassium ion binding; TAS:BHF-UCL.
DR GO; GO:0044325; F:transmembrane transporter binding; IPI:BHF-UCL.
DR GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:BHF-UCL.
DR GO; GO:0006006; P:glucose metabolic process; IMP:BHF-UCL.
DR GO; GO:0098662; P:inorganic cation transmembrane transport; ISS:ARUK-UCL.
DR GO; GO:0046676; P:negative regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0050877; P:nervous system process; IMP:BHF-UCL.
DR GO; GO:1990573; P:potassium ion import across plasma membrane; ISS:BHF-UCL.
DR GO; GO:0071805; P:potassium ion transmembrane transport; IDA:BHF-UCL.
DR GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0034765; P:regulation of ion transmembrane transport; IBA:GO_Central.
DR GO; GO:0042391; P:regulation of membrane potential; IDA:BHF-UCL.
DR GO; GO:0033198; P:response to ATP; IDA:BHF-UCL.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:BHF-UCL.
DR Gene3D; 2.60.40.1400; -; 1.
DR InterPro; IPR014756; Ig_E-set.
DR InterPro; IPR041647; IRK_C.
DR InterPro; IPR016449; K_chnl_inward-rec_Kir.
DR InterPro; IPR003279; K_chnl_inward-rec_Kir6.2.
DR InterPro; IPR013518; K_chnl_inward-rec_Kir_cyto.
DR InterPro; IPR040445; Kir_TM.
DR PANTHER; PTHR11767; PTHR11767; 1.
DR PANTHER; PTHR11767:SF44; PTHR11767:SF44; 1.
DR Pfam; PF01007; IRK; 1.
DR Pfam; PF17655; IRK_C; 1.
DR PIRSF; PIRSF005465; GIRK_kir; 1.
DR PRINTS; PR01332; KIR62CHANNEL.
DR PRINTS; PR01320; KIRCHANNEL.
DR SUPFAM; SSF81296; SSF81296; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Diabetes mellitus; Disease variant;
KW Ion channel; Ion transport; Membrane; Phosphoprotein; Potassium;
KW Potassium transport; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Voltage-gated channel.
FT CHAIN 1..390
FT /note="ATP-sensitive inward rectifier potassium channel 11"
FT /id="PRO_0000154957"
FT TOPO_DOM 1..68
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 69..93
FT /note="Helical; Name=M1"
FT /evidence="ECO:0000250"
FT TOPO_DOM 94..116
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT INTRAMEM 117..128
FT /note="Helical; Pore-forming; Name=H5"
FT /evidence="ECO:0000250"
FT INTRAMEM 129..135
FT /note="Pore-forming"
FT /evidence="ECO:0000250"
FT TOPO_DOM 136..144
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 145..166
FT /note="Helical; Name=M2"
FT /evidence="ECO:0000250"
FT TOPO_DOM 167..390
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT MOTIF 130..135
FT /note="Selectivity filter"
FT /evidence="ECO:0000250"
FT SITE 160
FT /note="Role in the control of polyamine-mediated channel
FT gating and in the blocking by intracellular magnesium"
FT /evidence="ECO:0000250"
FT MOD_RES 341
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:18280666"
FT MOD_RES 385
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:18280666"
FT VAR_SEQ 1..87
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_045270"
FT VARIANT 10
FT /note="E -> K (in dbSNP:rs587783667)"
FT /evidence="ECO:0000269|PubMed:9032109"
FT /id="VAR_008659"
FT VARIANT 18
FT /note="A -> G (in dbSNP:rs41309072)"
FT /id="VAR_055978"
FT VARIANT 23
FT /note="K -> E (in dbSNP:rs5219)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:15807877,
FT ECO:0000269|PubMed:16429405, ECO:0000269|PubMed:7502040,
FT ECO:0000269|PubMed:8897013, ECO:0000269|PubMed:9032109"
FT /id="VAR_008660"
FT VARIANT 34
FT /note="R -> H (in HHF2; dbSNP:rs141145502)"
FT /evidence="ECO:0000269|PubMed:15807877"
FT /id="VAR_031329"
FT VARIANT 35
FT /note="F -> L (in PNDM2; dbSNP:rs193929333)"
FT /evidence="ECO:0000269|PubMed:15448107"
FT /id="VAR_026498"
FT VARIANT 35
FT /note="F -> V (in PNDM2; dbSNP:rs193929333)"
FT /evidence="ECO:0000269|PubMed:15448106"
FT /id="VAR_026499"
FT VARIANT 40
FT /note="G -> D (in HHF2; dbSNP:rs1001873841)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031330"
FT VARIANT 42
FT /note="C -> R (in TNDM3; increased spontaneous open
FT probability; reduced ATP sensitivity; reduced expression at
FT the cell surface of the functional ATP-sensitive form;
FT dbSNP:rs80356610)"
FT /evidence="ECO:0000269|PubMed:15784703"
FT /id="VAR_031331"
FT VARIANT 46
FT /note="H -> Y (in PNDM2)"
FT /evidence="ECO:0000269|PubMed:16609879,
FT ECO:0000269|PubMed:17213273"
FT /id="VAR_031332"
FT VARIANT 50
FT /note="R -> P (in PNDM2; decreased inhibition by ATP;
FT enhanced activation by Mg(2+); increased current;
FT dbSNP:rs80356611)"
FT /evidence="ECO:0000269|PubMed:15580558,
FT ECO:0000269|PubMed:16731833"
FT /id="VAR_026500"
FT VARIANT 50
FT /note="R -> Q (in PNDM2; decreased inhibition by ATP;
FT enhanced activation by Mg(2+); increased current;
FT dbSNP:rs80356611)"
FT /evidence="ECO:0000269|PubMed:16609879,
FT ECO:0000269|PubMed:16731833"
FT /id="VAR_031333"
FT VARIANT 52
FT /note="Q -> R (in PNDM2; with neurologic features; produces
FT larger current and more change in ATP sensitivity than
FT mutation associated with mild disease C-201;
FT dbSNP:rs193929337)"
FT /evidence="ECO:0000269|PubMed:15115830,
FT ECO:0000269|PubMed:15583126, ECO:0000269|PubMed:16609879"
FT /id="VAR_026501"
FT VARIANT 53
FT /note="G -> D (in PNDM2; with neurologic features;
FT dbSNP:rs80356615)"
FT /evidence="ECO:0000269|PubMed:16609879"
FT /id="VAR_031334"
FT VARIANT 53
FT /note="G -> R (in TNDM3; reduction in the sensitivity to
FT ATP when compared with wild-type; dbSNP:rs80356613)"
FT /evidence="ECO:0000269|PubMed:15718250"
FT /id="VAR_026502"
FT VARIANT 53
FT /note="G -> S (in TNDM3; reduction in the sensitivity to
FT ATP when compared with wild-type; dbSNP:rs80356613)"
FT /evidence="ECO:0000269|PubMed:15718250"
FT /id="VAR_026503"
FT VARIANT 55
FT /note="F -> L (in HHF2; does neither affect channel
FT expression nor channel response to MgADP;
FT dbSNP:rs1343400778)"
FT /evidence="ECO:0000269|PubMed:16332676,
FT ECO:0000269|PubMed:18596924"
FT /id="VAR_031335"
FT VARIANT 59
FT /note="V -> G (in PNDM2; with neurologic features; produces
FT larger current and more change in ATP sensitivity than
FT mutation associated with mild disease C-201; decreases ATP
FT sensitivity indirectly by favoring the open conformation of
FT the channel; dbSNP:rs80356617)"
FT /evidence="ECO:0000269|PubMed:15115830,
FT ECO:0000269|PubMed:15583126, ECO:0000269|PubMed:16609879"
FT /id="VAR_026504"
FT VARIANT 59
FT /note="V -> M (in PNDM2; with neurologic features;
FT dbSNP:rs80356616)"
FT /evidence="ECO:0000269|PubMed:15115830,
FT ECO:0000269|PubMed:15448106, ECO:0000269|PubMed:15448107,
FT ECO:0000269|PubMed:15580558, ECO:0000269|PubMed:16609879"
FT /id="VAR_026505"
FT VARIANT 60
FT /note="F -> Y (in PNDM2; found in a patient who also
FT carries L-64 in cis; thought to be the pathogenic mutation
FT in this double allele; displays gain of function; increases
FT the intrinsic channel open probability and decreases
FT sensitivity toward ATP inhibition; variant L-64 associated
FT in cis is thought to ameliorate the effect of the Y-60
FT mutation on the channel ATP sensitivity;
FT dbSNP:rs387906783)"
FT /evidence="ECO:0000269|PubMed:20022885"
FT /id="VAR_073681"
FT VARIANT 64
FT /note="V -> L (in PNDM2; found in a patient who also
FT carries Y-60 in cis; unknown pathological significance;
FT only subtle effects, if any, on channel ATP sensitivity;
FT thought to attenuate the deleterious effect of the Y-60
FT mutation associated in cis on the channel ATP sensitivity;
FT dbSNP:rs115716690)"
FT /evidence="ECO:0000269|PubMed:20022885,
FT ECO:0000269|PubMed:28842488"
FT /id="VAR_073682"
FT VARIANT 67
FT /note="K -> N (in HHF2; dbSNP:rs747719667)"
FT /evidence="ECO:0000269|PubMed:12364426"
FT /id="VAR_026506"
FT VARIANT 91
FT /note="W -> R (in HHF2)"
FT /evidence="ECO:0000269|PubMed:10204114"
FT /id="VAR_026507"
FT VARIANT 101
FT /note="A -> D (in HHF2; dbSNP:rs1014454531)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031336"
FT VARIANT 116
FT /note="S -> P (in HHF2)"
FT /evidence="ECO:0000269|PubMed:16357843"
FT /id="VAR_031337"
FT VARIANT 134
FT /note="G -> A (in HHF2)"
FT /evidence="ECO:0000269|PubMed:15562009"
FT /id="VAR_031338"
FT VARIANT 136
FT /note="R -> L (in HHF2; dbSNP:rs1479483693)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031339"
FT VARIANT 147
FT /note="L -> P (in HHF2; dbSNP:rs28936678)"
FT /evidence="ECO:0000269|PubMed:7847376,
FT ECO:0000269|PubMed:8923010"
FT /id="VAR_001557"
FT VARIANT 148
FT /note="I -> S"
FT /evidence="ECO:0000269|PubMed:15807877,
FT ECO:0000269|PubMed:7502040"
FT /id="VAR_031340"
FT VARIANT 156
FT /note="G -> R (in HHF2; dbSNP:rs1404429785)"
FT /evidence="ECO:0000269|PubMed:18596924"
FT /id="VAR_073683"
FT VARIANT 164
FT /note="L -> P (in PNDM2)"
FT /evidence="ECO:0000269|PubMed:16609879,
FT ECO:0000269|PubMed:17213273"
FT /id="VAR_031341"
FT VARIANT 166
FT /note="C -> Y (in PNDM2; individual also diagnosed with
FT West syndrome; dbSNP:rs80356618)"
FT /evidence="ECO:0000269|PubMed:16609879"
FT /id="VAR_031342"
FT VARIANT 167
FT /note="I -> L (in PNDM2; has severely impaired sensitivity
FT to ATP and markedly increases open channel probability;
FT dbSNP:rs80356620)"
FT /evidence="ECO:0000269|PubMed:17652641"
FT /id="VAR_073684"
FT VARIANT 170
FT /note="K -> N (in PNDM2; dbSNP:rs80356622)"
FT /evidence="ECO:0000269|PubMed:15580558"
FT /id="VAR_026508"
FT VARIANT 170
FT /note="K -> R (in PNDM2; dbSNP:rs80356621)"
FT /evidence="ECO:0000269|PubMed:15580558"
FT /id="VAR_026509"
FT VARIANT 170
FT /note="K -> T (in PNDM2)"
FT /evidence="ECO:0000269|PubMed:16609879"
FT /id="VAR_031343"
FT VARIANT 182
FT /note="I -> V (in TNDM3; reduction in the sensitivity to
FT ATP when compared with wild-type; dbSNP:rs193929348)"
FT /evidence="ECO:0000269|PubMed:15718250"
FT /id="VAR_026510"
FT VARIANT 195
FT /note="R -> H (in dbSNP:rs5217)"
FT /id="VAR_014929"
FT VARIANT 201
FT /note="R -> C (in PNDM2; with neurologic features; produces
FT smaller current and less change in ATP sensitivity than
FT mutations associated with severe disease R-52 and G-59;
FT dbSNP:rs80356625)"
FT /evidence="ECO:0000269|PubMed:15115830,
FT ECO:0000269|PubMed:15292329, ECO:0000269|PubMed:15448107,
FT ECO:0000269|PubMed:15580558, ECO:0000269|PubMed:15583126,
FT ECO:0000269|PubMed:16609879"
FT /id="VAR_026511"
FT VARIANT 201
FT /note="R -> H (in PNDM2; ability of ATP to block mutant
FT channels greatly reduced; dbSNP:rs80356624)"
FT /evidence="ECO:0000269|PubMed:15115830,
FT ECO:0000269|PubMed:15448106, ECO:0000269|PubMed:15448107,
FT ECO:0000269|PubMed:16609879, ECO:0000269|PubMed:17213273"
FT /id="VAR_026512"
FT VARIANT 201
FT /note="R -> L (in PNDM2; dbSNP:rs80356624)"
FT /evidence="ECO:0000269|PubMed:16609879"
FT /id="VAR_031344"
FT VARIANT 204
FT /note="D -> E (in HHF2; dbSNP:rs577757932)"
FT /evidence="ECO:0000269|PubMed:18596924"
FT /id="VAR_073685"
FT VARIANT 227
FT /note="E -> K (in MODY13; dbSNP:rs587783672)"
FT /evidence="ECO:0000269|PubMed:22701567"
FT /id="VAR_073686"
FT VARIANT 254
FT /note="P -> L (in HHF2; impairs trafficking of the mutant
FT channel; dbSNP:rs104894237)"
FT /evidence="ECO:0000269|PubMed:15579781"
FT /id="VAR_026513"
FT VARIANT 259
FT /note="H -> R (in HHF2; impairs trafficking and abolishes
FT channel function; dbSNP:rs104894248)"
FT /evidence="ECO:0000269|PubMed:15998776"
FT /id="VAR_031345"
FT VARIANT 266
FT /note="P -> L (in HHF2; dbSNP:rs1554901679)"
FT /evidence="ECO:0000269|PubMed:15562009"
FT /id="VAR_031346"
FT VARIANT 270
FT /note="L -> V (in dbSNP:rs1800467)"
FT /evidence="ECO:0000269|PubMed:8897013,
FT ECO:0000269|PubMed:9032109"
FT /id="VAR_008661"
FT VARIANT 282
FT /note="E -> K (in HHF2; prevents the ER export and surface
FT expression of the channel; dbSNP:rs267607196)"
FT /evidence="ECO:0000269|PubMed:19357197"
FT /id="VAR_073687"
FT VARIANT 296
FT /note="I -> L (in PNDM2; with neurologic features;
FT dbSNP:rs193929353)"
FT /evidence="ECO:0000269|PubMed:15115830,
FT ECO:0000269|PubMed:16609879"
FT /id="VAR_026514"
FT VARIANT 301
FT /note="R -> H (in HHF2; dbSNP:rs74339576)"
FT /evidence="ECO:0000269|PubMed:15562009,
FT ECO:0000269|PubMed:16357843"
FT /id="VAR_031347"
FT VARIANT 322
FT /note="E -> K (in PNDM2; dbSNP:rs193929355)"
FT /evidence="ECO:0000269|PubMed:15448107"
FT /id="VAR_026515"
FT VARIANT 330
FT /note="Y -> C (in PNDM2; dbSNP:rs193929356)"
FT /evidence="ECO:0000269|PubMed:15448106,
FT ECO:0000269|PubMed:15448107"
FT /id="VAR_026516"
FT VARIANT 330
FT /note="Y -> S (in PNDM2)"
FT /evidence="ECO:0000269|PubMed:16609879"
FT /id="VAR_031348"
FT VARIANT 333
FT /note="F -> I (in PNDM2; alters gating characteristics;
FT decreases sensitivity to inhibition by ATP and increases
FT intrinsic open probability; dbSNP:rs193929357)"
FT /evidence="ECO:0000269|PubMed:15448106,
FT ECO:0000269|PubMed:17855752"
FT /id="VAR_026517"
FT VARIANT 337
FT /note="V -> I (in dbSNP:rs5215)"
FT /evidence="ECO:0000269|PubMed:10391210,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:15807877, ECO:0000269|PubMed:16429405,
FT ECO:0000269|PubMed:7502040, ECO:0000269|PubMed:8897013,
FT ECO:0000269|PubMed:9032109"
FT /id="VAR_008662"
FT VARIANT 355
FT /note="L -> P (in NIDDM; Afro-Caribbean;
FT dbSNP:rs797045635)"
FT /evidence="ECO:0000269|PubMed:8897013"
FT /id="VAR_008663"
FT VARIANT 380
FT /note="P -> PKP (in NIDDM)"
FT /id="VAR_008664"
FT VARIANT 385
FT /note="S -> C (in dbSNP:rs41282930)"
FT /evidence="ECO:0000269|PubMed:8897013"
FT /id="VAR_008665"
FT MUTAGEN 64
FT /note="V->M: Displays gain of function; increased open
FT state stability, reduced ATP sensitivity and increased
FT channel activity; almost completely abolishes high affinity
FT sensitivity to glibenclamide, an inhibitor of ATP-sensitive
FT potassium channels."
FT /evidence="ECO:0000269|PubMed:28842488"
FT CONFLICT 370
FT /note="K -> E (in Ref. 2; BAG63046)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 390 AA; 43526 MW; 00F4E7D94432F282 CRC64;
MLSRKGIIPE EYVLTRLAED PAKPRYRARQ RRARFVSKKG NCNVAHKNIR EQGRFLQDVF
TTLVDLKWPH TLLIFTMSFL CSWLLFAMAW WLIAFAHGDL APSEGTAEPC VTSIHSFSSA
FLFSIEVQVT IGFGGRMVTE ECPLAILILI VQNIVGLMIN AIMLGCIFMK TAQAHRRAET
LIFSKHAVIA LRHGRLCFML RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM
ENGVGGNSIF LVAPLIIYHV IDANSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA
RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTVKVP TPLCTARQLD EDHSLLEALT
LASARGPLRK RSVPMAKAKP KFSISPDSLS
