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Database: UniProt
Entry: KCJ11_HUMAN
LinkDB: KCJ11_HUMAN
Original site: 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   27-SEP-2005, sequence version 2.
DT   13-NOV-2019, entry version 205.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT SER-148.
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.,
RA   Gonzalez G., Aguilar-Bryan L., Seino S., Bryan J.;
RT   "Reconstitution of IKATP: an inward rectifier subunit plus the
RT   sulfonylurea receptor.";
RL   Science 270:1166-1170(1995).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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], AND VARIANTS LYS-23 AND
RP   VAL-337.
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.,
RA   Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E.,
RA   FitzGerald M.G., Jaffe D.B., LaButti K., Nicol R., Park H.-S.,
RA   Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W.,
RA   Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S.,
RA   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).
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
RT   project: 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
RT   the 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
RT   nucleotides.";
RL   Biophys. J. 84:266-276(2003).
RN   [7]
RP   INVOLVEMENT IN PNDM, VARIANT PNDM LEU-167, AND CHARACTERIZATION OF
RP   VARIANT PNDM 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
RP   VARIANT 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 PNDM, VARIANTS PNDM TYR-60 AND LEU-64, AND
RP   CHARACTERIZATION OF VARIANTS PNDM 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
RT   with 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
RT   disease.";
RL   Hum. Mutat. 13:351-361(1999).
RN   [12]
RP   FUNCTION, CHARACTERIZATION OF VARIANT PNDM ILE-333, AND INTERACTION
RP   WITH 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
RT   KCNJ11 as the thirteenth MODY gene.";
RL   PLoS ONE 7:E37423-E37423(2012).
RN   [15]
RP   FUNCTION, CHARACTERIZATION OF VARIANT PNDM 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.,
RA   Nichols C.G.;
RT   "Conserved functional consequences of disease-associated mutations in
RT   the slide-helix of Kir6.1 and Kir6.2 subunits of the ATP-sensitive
RT   potassium 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
RT   to 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 LYS-23;
RP   VAL-270; VAL-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-
RT   cell ATP-sensitive K-channel: no association with NIDDM in white
RT   Caucasian subjects or evidence of abnormal function when expressed in
RT   vitro.";
RL   Diabetologia 39:1233-1236(1996).
RN   [19]
RP   VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337.
RX   PubMed=9032109; DOI=10.2337/diab.46.3.502;
RA   Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H.,
RA   Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N.,
RA   Seino S., Permutt M.A.;
RT   "Sequence variants in the pancreatic islet beta-cell inwardly
RT   rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of
RT   role in Caucasian 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 LYS-23 AND VAL-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
RT   blood-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.,
RA   Otonkoski T.;
RT   "Acute insulin response tests for the differential diagnosis of
RT   congenital hyperinsulinism.";
RL   J. Clin. Endocrinol. Metab. 87:4502-4507(2002).
RN   [23]
RP   VARIANTS PNDM 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.,
RA   Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I.,
RA   Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R.;
RT   "Permanent neonatal diabetes due to mutations in KCNJ11 encoding
RT   Kir6.2: patient characteristics and initial response to sulfonylurea
RT   therapy.";
RL   Diabetes 53:2713-2718(2004).
RN   [24]
RP   VARIANTS PNDM 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
RT   a large cohort of French patients.";
RL   Diabetes 53:2719-2722(2004).
RN   [25]
RP   VARIANT PNDM 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.,
RA   Costa T., 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
RT   the 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.,
RA   Heyman M., Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O.,
RA   Nahari E., Potikha T., Zangen D., Tenenbaum-Rakover Y., de Vries L.,
RA   Argente J., Gracia R., Landau H., Eliakim A., Lindley K., Dunne M.J.,
RA   Aguilar-Bryan L., Glaser B.;
RT   "Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and
RT   evidence for additional locus heterogeneity.";
RL   J. Clin. Endocrinol. Metab. 89:6224-6234(2004).
RN   [27]
RP   VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296,
RP   AND CHARACTERIZATION OF VARIANT PNDM 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.,
RA   Aisenberg J., Ellard S., Njoelstad P.R., Ashcroft F.M.,
RA   Hattersley A.T.;
RT   "Activating mutations in the gene encoding the ATP-sensitive
RT   potassium-channel subunit Kir6.2 and permanent neonatal diabetes.";
RL   N. Engl. J. Med. 350:1838-1849(2004).
RN   [28]
RP   ERRATUM.
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.,
RA   Aisenberg J., Ellard S., Njoelstad P.R., Ashcroft F.M.,
RA   Hattersley A.T.;
RL   N. Engl. J. Med. 351:1470-1470(2004).
RN   [29]
RP   CHARACTERIZATION OF VARIANTS PNDM 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
RT   or 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 LYS-23; SER-148 AND VAL-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
RP   VARIANTS 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.,
RA   Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H.,
RA   Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M.,
RA   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 PNDM 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.,
RA   Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O.,
RA   Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F.;
RT   "KCNJ11 activating mutations in Italian patients with permanent
RT   neonatal 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.,
RA   Thornton P.S., Stanley C.A.;
RT   "Genotype-phenotype correlations in children with congenital
RT   hyperinsulinism due to recessive mutations of the adenosine
RT   triphosphate-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.,
RA   Akazawa Y., 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
RT   2 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.,
RA   Bancila V., 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
RT   impairing trafficking and function.";
RL   J. Clin. Endocrinol. Metab. 90:5401-5406(2005).
RN   [36]
RP   VARIANTS PNDM GLN-50 AND PRO-50, AND CHARACTERIZATION OF VARIANTS PNDM
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.,
RA   Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F.,
RA   Ashcroft F.M.;
RT   "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause
RT   neonatal diabetes produce different functional effects.";
RL   Diabetes 55:1705-1712(2006).
RN   [37]
RP   VARIANTS PNDM 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
RT   diabetes diagnosed in the first 6 months of life, with the phenotype
RT   determined by genotype.";
RL   Diabetologia 49:1190-1197(2006).
RN   [38]
RP   VARIANTS LYS-23 AND VAL-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
RT   Hyperinsulinism of 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
RT   reduces the intrinsic open probability of beta-cell ATP-sensitive
RT   potassium 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
RT   congenital hyperinsulinism.";
RL   Mod. Pathol. 19:122-129(2006).
RN   [41]
RP   VARIANTS PNDM 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.,
RA   Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E.,
RA   Pearson E., 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
CC       rectifier potassium channels are characterized by a greater
CC       tendency to allow potassium to flow into the cell rather than out
CC       of it. Their voltage dependence is regulated by the concentration
CC       of extracellular potassium; as external potassium is raised, the
CC       voltage range of the channel opening shifts to more positive
CC       voltages. The inward rectification is mainly due to the blockage
CC       of outward current by internal magnesium. Can be blocked by
CC       extracellular barium (By similarity). Subunit of ATP-sensitive
CC       potassium channels (KATP). Can form cardiac and smooth muscle-type
CC       KATP channels with ABCC9. KCNJ11 forms the channel pore while
CC       ABCC9 is required for activation and regulation. {ECO:0000250,
CC       ECO:0000269|PubMed:17855752, ECO:0000269|PubMed:28842488,
CC       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       Q09428-1:ABCC8; NbExp=2; IntAct=EBI-2866553, EBI-15807650;
CC       Q01484:ANK2; NbExp=6; IntAct=EBI-2866553, EBI-941975;
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
CC       that destabilize the closed states and reduce the ATP sensitivity.
CC       {ECO:0000269|PubMed:18280666}.
CC   -!- DISEASE: Familial hyperinsulinemic hypoglycemia 2 (HHF2)
CC       [MIM:601820]: Most common cause of persistent hypoglycemia in
CC       infancy. Unless early and aggressive intervention is undertaken,
CC       brain damage from recurrent episodes of hypoglycemia may occur.
CC       {ECO:0000269|PubMed:10204114, ECO:0000269|PubMed:12364426,
CC       ECO:0000269|PubMed:15562009, ECO:0000269|PubMed:15579781,
CC       ECO:0000269|PubMed:15807877, ECO:0000269|PubMed:15998776,
CC       ECO:0000269|PubMed:16332676, ECO:0000269|PubMed:16357843,
CC       ECO:0000269|PubMed:18596924, ECO:0000269|PubMed:19357197,
CC       ECO:0000269|PubMed:7847376, ECO:0000269|PubMed:8923010}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- DISEASE: Diabetes mellitus, permanent neonatal (PNDM)
CC       [MIM:606176]: A rare form of diabetes distinct from childhood-
CC       onset autoimmune diabetes mellitus type 1. It is characterized by
CC       insulin-requiring hyperglycemia that is diagnosed within the first
CC       months of life. Permanent neonatal diabetes requires lifelong
CC       therapy. {ECO:0000269|PubMed:15115830,
CC       ECO:0000269|PubMed:15292329, ECO:0000269|PubMed:15448106,
CC       ECO:0000269|PubMed:15448107, ECO:0000269|PubMed:15580558,
CC       ECO:0000269|PubMed:15583126, ECO:0000269|PubMed:16609879,
CC       ECO:0000269|PubMed:16731833, ECO:0000269|PubMed:17213273,
CC       ECO:0000269|PubMed:17652641, ECO:0000269|PubMed:17855752,
CC       ECO:0000269|PubMed:20022885, ECO:0000269|PubMed:28842488}.
CC       Note=The disease is caused by mutations affecting the gene
CC       represented in this entry.
CC   -!- DISEASE: Transient neonatal diabetes mellitus 3 (TNDM3)
CC       [MIM:610582]: Neonatal diabetes mellitus, defined as insulin-
CC       requiring hyperglycemia within the first month of life, is a rare
CC       entity. In about half of the neonates, diabetes is transient and
CC       resolves at a median age of 3 months, whereas the rest have a
CC       permanent form of diabetes. In a significant number of patients
CC       with transient neonatal diabetes mellitus, diabetes type 2 appears
CC       later in life. The onset and severity of TNDM3 is variable with
CC       childhood-onset diabetes, gestational diabetes or adult-onset
CC       diabetes described. {ECO:0000269|PubMed:15718250,
CC       ECO:0000269|PubMed:15784703}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Note=Defects in KCNJ11 may contribute to non-insulin-
CC       dependent diabetes mellitus (NIDDM), also known as diabetes
CC       mellitus type 2.
CC   -!- DISEASE: Maturity-onset diabetes of the young 13 (MODY13)
CC       [MIM:616329]: A form of diabetes that is characterized by an
CC       autosomal dominant mode of inheritance, onset in childhood or
CC       early adulthood (usually before 25 years of age), a primary defect
CC       in insulin secretion and frequent insulin-independence at the
CC       beginning of the disease. {ECO:0000269|PubMed:22701567}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- SIMILARITY: Belongs to the inward rectifier-type potassium channel
CC       (TC 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};
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   SMR; Q14654; -.
DR   BioGrid; 109969; 12.
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   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   Ensembl; ENST00000339994; ENSP00000345708; ENSG00000187486.
DR   Ensembl; ENST00000528731; ENSP00000434755; ENSG00000187486.
DR   GeneID; 3767; -.
DR   KEGG; hsa:3767; -.
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; HPA048891; -.
DR   MalaCards; KCNJ11; -.
DR   MIM; 600937; gene.
DR   MIM; 601820; phenotype.
DR   MIM; 606176; phenotype.
DR   MIM; 610582; phenotype.
DR   MIM; 616329; phenotype.
DR   neXtProt; NX_Q14654; -.
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; 552; MODY.
DR   Orphanet; 99885; Permanent neonatal diabetes mellitus.
DR   Orphanet; 99886; Transient neonatal diabetes mellitus.
DR   PharmGKB; PA217; -.
DR   eggNOG; KOG3827; Eukaryota.
DR   eggNOG; ENOG410XQ62; LUCA.
DR   HOGENOM; HOG000237325; -.
DR   InParanoid; Q14654; -.
DR   KO; K05004; -.
DR   OrthoDB; 1574389at2759; -.
DR   PhylomeDB; Q14654; -.
DR   TreeFam; TF313676; -.
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 dilated cardiomyopathy 10, familial atrial fibrillation 12 and hypertrichotic osteochondrodysplasia.
DR   Reactome; R-HSA-5683177; Defective ABCC8 can cause hypoglycemias and hyperglycemias.
DR   SignaLink; Q14654; -.
DR   SIGNOR; Q14654; -.
DR   ChiTaRS; KCNJ11; human.
DR   GeneWiki; Kir6.2; -.
DR   GenomeRNAi; 3767; -.
DR   Pharos; Q14654; -.
DR   PRO; PR:Q14654; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   Bgee; ENSG00000187486; Expressed in 99 organ(s), highest expression level in gastrocnemius.
DR   ExpressionAtlas; Q14654; baseline and differential.
DR   Genevisible; Q14654; HS.
DR   GO; GO:0001669; C:acrosomal vesicle; IEA:Ensembl.
DR   GO; GO:0030673; C:axolemma; IEA:Ensembl.
DR   GO; GO:0005623; C:cell; IEA:GOC.
DR   GO; GO:0070852; C:cell body fiber; IEA:Ensembl.
DR   GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR   GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR   GO; GO:0005768; C:endosome; IEA:Ensembl.
DR   GO; GO:0005887; C:integral component of plasma membrane; TAS:ProtInc.
DR   GO; GO:0014704; C:intercalated disc; IEA:Ensembl.
DR   GO; GO:0008282; C:inward rectifying potassium channel; IDA:BHF-UCL.
DR   GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR   GO; GO:0043209; C:myelin sheath; IEA:Ensembl.
DR   GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR   GO; GO:0005635; C:nuclear envelope; IEA:Ensembl.
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:0031072; F:heat shock protein binding; IEA:Ensembl.
DR   GO; GO:0005242; F:inward rectifier potassium channel activity; IBA:GO_Central.
DR   GO; GO:0044325; F:ion channel binding; IPI:BHF-UCL.
DR   GO; GO:0030955; F:potassium ion binding; TAS:BHF-UCL.
DR   GO; GO:0008022; F:protein C-terminus binding; IEA:Ensembl.
DR   GO; GO:0005249; F:voltage-gated potassium channel activity; IDA:BHF-UCL.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IEA:Ensembl.
DR   GO; GO:0071316; P:cellular response to nicotine; IEA:Ensembl.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0006006; P:glucose metabolic process; IMP:BHF-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:2001259; P:positive regulation of cation channel activity; IEA:Ensembl.
DR   GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl.
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:1903779; P:regulation of cardiac conduction; TAS:Reactome.
DR   GO; GO:0050796; P:regulation of insulin secretion; IMP:BHF-UCL.
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:0042493; P:response to drug; IMP:BHF-UCL.
DR   GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR   GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR   GO; GO:0033574; P:response to testosterone; IEA:Ensembl.
DR   GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
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; Complete proteome;
KW   Diabetes mellitus; Disease mutation; Ion channel; Ion transport;
KW   Membrane; Phosphoprotein; Polymorphism; Potassium;
KW   Potassium transport; Reference proteome; Transmembrane;
KW   Transmembrane helix; Transport; Voltage-gated channel.
FT   CHAIN         1    390       ATP-sensitive inward rectifier potassium
FT                                channel 11.
FT                                /FTId=PRO_0000154957.
FT   TOPO_DOM      1     68       Cytoplasmic. {ECO:0000250}.
FT   TRANSMEM     69     93       Helical; Name=M1. {ECO:0000250}.
FT   TOPO_DOM     94    116       Extracellular. {ECO:0000250}.
FT   INTRAMEM    117    128       Helical; Pore-forming; Name=H5.
FT                                {ECO:0000250}.
FT   INTRAMEM    129    135       Pore-forming. {ECO:0000250}.
FT   TOPO_DOM    136    144       Extracellular. {ECO:0000250}.
FT   TRANSMEM    145    166       Helical; Name=M2. {ECO:0000250}.
FT   TOPO_DOM    167    390       Cytoplasmic. {ECO:0000250}.
FT   MOTIF       130    135       Selectivity filter. {ECO:0000250}.
FT   SITE        160    160       Role in the control of polyamine-mediated
FT                                channel gating and in the blocking by
FT                                intracellular magnesium. {ECO:0000250}.
FT   MOD_RES     341    341       Phosphothreonine; by MAPK1.
FT                                {ECO:0000269|PubMed:18280666}.
FT   MOD_RES     385    385       Phosphoserine; by MAPK1.
FT                                {ECO:0000269|PubMed:18280666}.
FT   VAR_SEQ       1     87       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_045270.
FT   VARIANT      10     10       E -> K (rare polymorphism;
FT                                dbSNP:rs587783667).
FT                                {ECO:0000269|PubMed:9032109}.
FT                                /FTId=VAR_008659.
FT   VARIANT      18     18       A -> G (in dbSNP:rs41309072).
FT                                /FTId=VAR_055978.
FT   VARIANT      23     23       E -> K (linked to V-337; dbSNP:rs5219).
FT                                {ECO:0000269|PubMed:10391210,
FT                                ECO:0000269|PubMed:15807877,
FT                                ECO:0000269|PubMed:16429405,
FT                                ECO:0000269|PubMed:16554811,
FT                                ECO:0000269|PubMed:8897013,
FT                                ECO:0000269|PubMed:9032109}.
FT                                /FTId=VAR_008660.
FT   VARIANT      34     34       R -> H (in HHF2; dbSNP:rs141145502).
FT                                {ECO:0000269|PubMed:15807877}.
FT                                /FTId=VAR_031329.
FT   VARIANT      35     35       F -> L (in PNDM; dbSNP:rs193929333).
FT                                {ECO:0000269|PubMed:15448107}.
FT                                /FTId=VAR_026498.
FT   VARIANT      35     35       F -> V (in PNDM; dbSNP:rs193929333).
FT                                {ECO:0000269|PubMed:15448106}.
FT                                /FTId=VAR_026499.
FT   VARIANT      40     40       G -> D (in HHF2; dbSNP:rs1001873841).
FT                                {ECO:0000269|PubMed:16357843}.
FT                                /FTId=VAR_031330.
FT   VARIANT      42     42       C -> R (in TNDM3; increased spontaneous
FT                                open probability; reduced ATP
FT                                sensitivity; reduced expression at the
FT                                cell surface of the functional ATP-
FT                                sensitive form; dbSNP:rs80356610).
FT                                {ECO:0000269|PubMed:15784703}.
FT                                /FTId=VAR_031331.
FT   VARIANT      46     46       H -> Y (in PNDM; one patient with mild
FT                                dysmorphic features).
FT                                {ECO:0000269|PubMed:16609879,
FT                                ECO:0000269|PubMed:17213273}.
FT                                /FTId=VAR_031332.
FT   VARIANT      50     50       R -> P (in PNDM; decreased inhibition by
FT                                ATP; enhanced activation by Mg(2+);
FT                                increased current; one patient with
FT                                developmental delay; dbSNP:rs80356611).
FT                                {ECO:0000269|PubMed:15580558,
FT                                ECO:0000269|PubMed:16731833}.
FT                                /FTId=VAR_026500.
FT   VARIANT      50     50       R -> Q (in PNDM; decreased inhibition by
FT                                ATP; enhanced activation by Mg(2+);
FT                                increased current; dbSNP:rs80356611).
FT                                {ECO:0000269|PubMed:16609879,
FT                                ECO:0000269|PubMed:16731833}.
FT                                /FTId=VAR_031333.
FT   VARIANT      52     52       Q -> R (in PNDM; with developmental delay
FT                                and epilepsy; produces larger current and
FT                                more change in ATP sensitivity than
FT                                mutation associated with mild disease C-
FT                                201; dbSNP:rs193929337).
FT                                {ECO:0000269|PubMed:15115830,
FT                                ECO:0000269|PubMed:15583126,
FT                                ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_026501.
FT   VARIANT      53     53       G -> D (in PNDM; with developmental delay
FT                                and epilepsy; dbSNP:rs80356615).
FT                                {ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_031334.
FT   VARIANT      53     53       G -> R (in TNDM3; also found in a family
FT                                member with PNDM; reduction in the
FT                                sensitivity to ATP when compared with
FT                                wild-type; dbSNP:rs80356613).
FT                                {ECO:0000269|PubMed:15718250}.
FT                                /FTId=VAR_026502.
FT   VARIANT      53     53       G -> S (in TNDM3; also found in a family
FT                                member with PNDM; reduction in the
FT                                sensitivity to ATP when compared with
FT                                wild-type; dbSNP:rs80356613).
FT                                {ECO:0000269|PubMed:15718250}.
FT                                /FTId=VAR_026503.
FT   VARIANT      55     55       F -> L (in HHF2; does neither affect
FT                                channel expression nor channel response
FT                                to MgADP; dbSNP:rs1343400778).
FT                                {ECO:0000269|PubMed:16332676,
FT                                ECO:0000269|PubMed:18596924}.
FT                                /FTId=VAR_031335.
FT   VARIANT      59     59       V -> G (in PNDM; with developmental delay
FT                                and epilepsy; with neurologic features;
FT                                produces larger current and more change
FT                                in ATP sensitivity than mutation
FT                                associated with mild disease C-201;
FT                                decreases ATP sensitivity indirectly by
FT                                favoring the open conformation of the
FT                                channel; dbSNP:rs80356617).
FT                                {ECO:0000269|PubMed:15115830,
FT                                ECO:0000269|PubMed:15583126,
FT                                ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_026504.
FT   VARIANT      59     59       V -> M (in PNDM; four patients with
FT                                developmental delay and muscle weakness;
FT                                dbSNP:rs80356616).
FT                                {ECO:0000269|PubMed:15115830,
FT                                ECO:0000269|PubMed:15448106,
FT                                ECO:0000269|PubMed:15448107,
FT                                ECO:0000269|PubMed:15580558,
FT                                ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_026505.
FT   VARIANT      60     60       F -> Y (in PNDM; found in a patient who
FT                                also carries L-64 in cis; thought to be
FT                                the pathogenic mutation in this double
FT                                allele; displays gain of function;
FT                                increases the intrinsic channel open
FT                                probability and decreases sensitivity
FT                                toward ATP inhibition; variant L-64
FT                                associated in cis is thought to
FT                                ameliorate the effect of the Y-60
FT                                mutation on the channel ATP sensitivity;
FT                                dbSNP:rs387906783).
FT                                {ECO:0000269|PubMed:20022885}.
FT                                /FTId=VAR_073681.
FT   VARIANT      64     64       V -> L (in PNDM; found in a patient who
FT                                also carries Y-60 in cis; unknown
FT                                pathological significance; only subtle
FT                                effects, if any, on channel ATP
FT                                sensitivity; thought to attenuate the
FT                                deleterious effect of the Y-60 mutation
FT                                associated in cis on the channel ATP
FT                                sensitivity; dbSNP:rs115716690).
FT                                {ECO:0000269|PubMed:20022885,
FT                                ECO:0000269|PubMed:28842488}.
FT                                /FTId=VAR_073682.
FT   VARIANT      67     67       K -> N (in HHF2; dbSNP:rs747719667).
FT                                {ECO:0000269|PubMed:12364426}.
FT                                /FTId=VAR_026506.
FT   VARIANT      91     91       W -> R (in HHF2).
FT                                {ECO:0000269|PubMed:10204114}.
FT                                /FTId=VAR_026507.
FT   VARIANT     101    101       A -> D (in HHF2; dbSNP:rs1014454531).
FT                                {ECO:0000269|PubMed:15562009,
FT                                ECO:0000269|PubMed:16357843}.
FT                                /FTId=VAR_031336.
FT   VARIANT     116    116       S -> P (in HHF2).
FT                                {ECO:0000269|PubMed:16357843}.
FT                                /FTId=VAR_031337.
FT   VARIANT     134    134       G -> A (in HHF2).
FT                                {ECO:0000269|PubMed:15562009}.
FT                                /FTId=VAR_031338.
FT   VARIANT     136    136       R -> L (in HHF2; dbSNP:rs1479483693).
FT                                {ECO:0000269|PubMed:15562009,
FT                                ECO:0000269|PubMed:16357843}.
FT                                /FTId=VAR_031339.
FT   VARIANT     147    147       L -> P (in HHF2; dbSNP:rs28936678).
FT                                {ECO:0000269|PubMed:7847376,
FT                                ECO:0000269|PubMed:8923010}.
FT                                /FTId=VAR_001557.
FT   VARIANT     148    148       I -> S. {ECO:0000269|PubMed:15807877,
FT                                ECO:0000269|PubMed:7502040}.
FT                                /FTId=VAR_031340.
FT   VARIANT     156    156       G -> R (in HHF2; dbSNP:rs1404429785).
FT                                {ECO:0000269|PubMed:18596924}.
FT                                /FTId=VAR_073683.
FT   VARIANT     164    164       L -> P (in PNDM).
FT                                {ECO:0000269|PubMed:16609879,
FT                                ECO:0000269|PubMed:17213273}.
FT                                /FTId=VAR_031341.
FT   VARIANT     166    166       C -> Y (in PNDM; individual also
FT                                diagnosed with West syndrome;
FT                                dbSNP:rs80356618).
FT                                {ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_031342.
FT   VARIANT     167    167       I -> L (in PNDM; has severely impaired
FT                                sensitivity to ATP and markedly increases
FT                                open channel probability;
FT                                dbSNP:rs80356620).
FT                                {ECO:0000269|PubMed:17652641}.
FT                                /FTId=VAR_073684.
FT   VARIANT     170    170       K -> N (in PNDM; dbSNP:rs80356622).
FT                                {ECO:0000269|PubMed:15580558}.
FT                                /FTId=VAR_026508.
FT   VARIANT     170    170       K -> R (in PNDM; dbSNP:rs80356621).
FT                                {ECO:0000269|PubMed:15580558}.
FT                                /FTId=VAR_026509.
FT   VARIANT     170    170       K -> T (in PNDM).
FT                                {ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_031343.
FT   VARIANT     182    182       I -> V (in TNDM3; reduction in the
FT                                sensitivity to ATP when compared with
FT                                wild-type; dbSNP:rs193929348).
FT                                {ECO:0000269|PubMed:15718250}.
FT                                /FTId=VAR_026510.
FT   VARIANT     195    195       R -> H (in dbSNP:rs5217).
FT                                /FTId=VAR_014929.
FT   VARIANT     201    201       R -> C (in PNDM; two individuals with
FT                                developmental delay; produces smaller
FT                                current and less change in ATP
FT                                sensitivity than mutations associated
FT                                with severe disease R-52 and G-59;
FT                                dbSNP:rs80356625).
FT                                {ECO:0000269|PubMed:15115830,
FT                                ECO:0000269|PubMed:15292329,
FT                                ECO:0000269|PubMed:15448107,
FT                                ECO:0000269|PubMed:15580558,
FT                                ECO:0000269|PubMed:15583126,
FT                                ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_026511.
FT   VARIANT     201    201       R -> H (in PNDM; ability of ATP to block
FT                                mutant channels greatly reduced;
FT                                dbSNP:rs80356624).
FT                                {ECO:0000269|PubMed:15115830,
FT                                ECO:0000269|PubMed:15448106,
FT                                ECO:0000269|PubMed:15448107,
FT                                ECO:0000269|PubMed:16609879,
FT                                ECO:0000269|PubMed:17213273}.
FT                                /FTId=VAR_026512.
FT   VARIANT     201    201       R -> L (in PNDM; dbSNP:rs80356624).
FT                                {ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_031344.
FT   VARIANT     204    204       D -> E (in HHF2; dbSNP:rs577757932).
FT                                {ECO:0000269|PubMed:18596924}.
FT                                /FTId=VAR_073685.
FT   VARIANT     227    227       E -> K (in MODY13; dbSNP:rs587783672).
FT                                {ECO:0000269|PubMed:22701567}.
FT                                /FTId=VAR_073686.
FT   VARIANT     254    254       P -> L (in HHF2; impairs trafficking of
FT                                the mutant channel; dbSNP:rs104894237).
FT                                {ECO:0000269|PubMed:15579781}.
FT                                /FTId=VAR_026513.
FT   VARIANT     259    259       H -> R (in HHF2; impairs trafficking and
FT                                abolishes channel function;
FT                                dbSNP:rs104894248).
FT                                {ECO:0000269|PubMed:15998776}.
FT                                /FTId=VAR_031345.
FT   VARIANT     266    266       P -> L (in HHF2; dbSNP:rs1554901679).
FT                                {ECO:0000269|PubMed:15562009}.
FT                                /FTId=VAR_031346.
FT   VARIANT     270    270       L -> V (in dbSNP:rs1800467).
FT                                {ECO:0000269|PubMed:8897013,
FT                                ECO:0000269|PubMed:9032109}.
FT                                /FTId=VAR_008661.
FT   VARIANT     282    282       E -> K (in HHF2; prevents the ER export
FT                                and surface expression of the channel;
FT                                dbSNP:rs267607196).
FT                                {ECO:0000269|PubMed:19357197}.
FT                                /FTId=VAR_073687.
FT   VARIANT     296    296       I -> L (in PNDM; with developmental delay
FT                                and epilepsy; dbSNP:rs193929353).
FT                                {ECO:0000269|PubMed:15115830,
FT                                ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_026514.
FT   VARIANT     301    301       R -> H (in HHF2; dbSNP:rs74339576).
FT                                {ECO:0000269|PubMed:15562009,
FT                                ECO:0000269|PubMed:16357843}.
FT                                /FTId=VAR_031347.
FT   VARIANT     322    322       E -> K (in PNDM; dbSNP:rs193929355).
FT                                {ECO:0000269|PubMed:15448107}.
FT                                /FTId=VAR_026515.
FT   VARIANT     330    330       Y -> C (in PNDM; dbSNP:rs193929356).
FT                                {ECO:0000269|PubMed:15448106,
FT                                ECO:0000269|PubMed:15448107}.
FT                                /FTId=VAR_026516.
FT   VARIANT     330    330       Y -> S (in PNDM).
FT                                {ECO:0000269|PubMed:16609879}.
FT                                /FTId=VAR_031348.
FT   VARIANT     333    333       F -> I (in PNDM; alters gating
FT                                characteristics, decreases sensitivity to
FT                                inhibition by ATP and increases intrinsic
FT                                open probability; dbSNP:rs193929357).
FT                                {ECO:0000269|PubMed:15448106,
FT                                ECO:0000269|PubMed:17855752}.
FT                                /FTId=VAR_026517.
FT   VARIANT     337    337       I -> V (linked to K-23; dbSNP:rs5215).
FT                                {ECO:0000269|PubMed:10391210,
FT                                ECO:0000269|PubMed:15807877,
FT                                ECO:0000269|PubMed:16429405,
FT                                ECO:0000269|PubMed:16554811,
FT                                ECO:0000269|PubMed:8897013,
FT                                ECO:0000269|PubMed:9032109}.
FT                                /FTId=VAR_008662.
FT   VARIANT     355    355       L -> P (in NIDDM; Afro-Caribbean;
FT                                dbSNP:rs797045635).
FT                                {ECO:0000269|PubMed:8897013}.
FT                                /FTId=VAR_008663.
FT   VARIANT     380    380       P -> PKP (in NIDDM).
FT                                /FTId=VAR_008664.
FT   VARIANT     385    385       S -> C (in dbSNP:rs41282930).
FT                                {ECO:0000269|PubMed:8897013}.
FT                                /FTId=VAR_008665.
FT   MUTAGEN      64     64       V->M: Displays gain of function;
FT                                increased open state stability, reduced
FT                                ATP sensitivity and increased channel
FT                                activity; almost completely abolishes
FT                                high affinity sensitivity to
FT                                glibenclamide, an inhibitor of ATP-
FT                                sensitive potassium channels.
FT                                {ECO:0000269|PubMed:28842488}.
FT   CONFLICT    370    370       K -> E (in Ref. 2; BAG63046).
FT                                {ECO:0000305}.
SQ   SEQUENCE   390 AA;  43541 MW;  8345E7DBCE897344 CRC64;
     MLSRKGIIPE EYVLTRLAED PAEPRYRARQ 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 SKFGNTIKVP TPLCTARQLD EDHSLLEALT
     LASARGPLRK RSVPMAKAKP KFSISPDSLS
//
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