KCNJ11

Functionⁱ

This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium (By similarity). Subunit of ATP-sensitive potassium channels (KATP). Can form cardiac and smooth muscle-type KATP channels with ABCC9. KCNJ11 forms the channel pore while ABCC9 is required for activation and regulation.By similarity2 Publications

Sites

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Siteⁱ	160 – 160	1	Role in the control of polyamine-mediated channel gating and in the blocking by intracellular magnesiumBy similarity

GO - Molecular functionⁱ

ankyrin binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 20610380
ATP-activated inward rectifier potassium channel activity Source: BHF-UCL
ATP binding
Source: BHF-UCL
Inferred from sequence or structural similarityⁱ
- 12860923
ion channel binding
Source: BHF-UCL
Inferred from physical interactionⁱ
- 20610380
potassium ion binding
Source: BHF-UCL
Traceable author statementⁱ
- 8923010
voltage-gated potassium channel activity
Source: BHF-UCL
Inferred from direct assayⁱ
- 19805355

Enzyme and pathway databases

Reactomeⁱ	REACT_18325. Regulation of insulin secretion. REACT_75775. ATP sensitive Potassium channels.
SignaLinkⁱ	Q14654.

Names & Taxonomyⁱ

Protein namesⁱ	Recommended name: ATP-sensitive inward rectifier potassium channel 11 Alternative name(s): IKATP Inward rectifier K(+) channel Kir6.2 Potassium channel, inwardly rectifying subfamily J member 11
Gene namesⁱ	Name:KCNJ11
Organismⁱ	Homo sapiens (Human)
Taxonomic identifierⁱ	9606 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo
Proteomesⁱ	UP000005640: Chromosome 11

Organism-specific databases

HGNCⁱ	HGNC:6257. KCNJ11.

HGNCⁱ

HGNC:6257. KCNJ11.

Subcellular locationⁱ

Membrane; Multi-pass membrane protein

Topology

Feature key	Position(s)	Length	Description	Actions
Topological domainⁱ	1 – 68	68	CytoplasmicBy similarity	Add BLAST
Transmembraneⁱ	69 – 93	25	Helical; Name=M1By similarity	Add BLAST
Topological domainⁱ	94 – 116	23	ExtracellularBy similarity	Add BLAST
Intramembraneⁱ	117 – 128	12	Helical; Pore-forming; Name=H5By similarity	Add BLAST
Intramembraneⁱ	129 – 135	7	Pore-formingBy similarity
Topological domainⁱ	136 – 144	9	ExtracellularBy similarity
Transmembraneⁱ	145 – 166	22	Helical; Name=M2By similarity	Add BLAST
Topological domainⁱ	167 – 390	224	CytoplasmicBy similarity	Add BLAST

GO - Cellular componentⁱ

ATP-sensitive potassium channel complex
Source: BHF-UCL
Inferred from direct assayⁱ
- 19805355
axolemma Source: Ensembl
cell body fiber Source: Ensembl
cytosol Source: Ensembl
endoplasmic reticulum Source: Ensembl
endosome Source: Ensembl
integral component of plasma membrane
Source: ProtInc
Traceable author statementⁱ
- 8923010
intercalated disc Source: Ensembl
mitochondrion Source: Ensembl
myelin sheath Source: Ensembl
neuronal cell body Source: Ensembl
nuclear envelope Source: Ensembl
plasma membrane
Source: BHF-UCL
Inferred from direct assayⁱ
- 19805355
T-tubule Source: BHF-UCL
voltage-gated potassium channel complex
Source: BHF-UCL
Inferred from direct assayⁱ
- 20610380

Complete GO annotation...

Keywords - Cellular componentⁱ

Membrane

Pathology & Biotechⁱ

Involvement in diseaseⁱ

Familial hyperinsulinemic hypoglycemia 2 (HHF2)

[MIM:601820]: Most common cause of persistent hypoglycemia in infancy. Unless early and aggressive intervention is undertaken, brain damage from recurrent episodes of hypoglycemia may occur.10 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	34 – 34	1	R → H in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.23 "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy." Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J. Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337.	VAR_031329
Natural variantⁱ	40 – 40	1	G → D in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031330
Natural variantⁱ	55 – 55	1	F → L in HHF2; does neither affect channel expression nor channel response to MgADP. 1 Publication Manual assertion based on experiment inⁱ Ref.32 "A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels." Lin Y.-W., MacMullen C., Ganguly A., Stanley C.A., Shyng S.-L. J. Biol. Chem. 281:3006-3012(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 LEU-55, CHARACTERIZATION OF VARIANT HHF2 LEU-55.	VAR_031335
Natural variantⁱ	67 – 67	1	K → N in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism." Huopio H., Jaeaeskelaeinen J., Komulainen J., Miettinen R., Kaerkkaeinen P., Laakso M., Tapanainen P., Voutilainen R., Otonkoski T. J. Clin. Endocrinol. Metab. 87:4502-4507(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 ASN-67.	VAR_026506
Natural variantⁱ	91 – 91	1	W → R in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.14 "Molecular biology of adenosine triphosphate-sensitive potassium channels." Aguilar-Bryan L., Bryan J. Endocr. Rev. 20:101-135(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 ARG-91.	VAR_026507
Natural variantⁱ	101 – 101	1	A → D in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301. Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031336
Natural variantⁱ	116 – 116	1	S → P in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031337
Natural variantⁱ	134 – 134	1	G → A in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.	VAR_031338
Natural variantⁱ	136 – 136	1	R → L in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301. Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031339
Natural variantⁱ	147 – 147	1	L → P in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.10 "Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy." Thomas P.M., Cote G.J., Hallman D.M., Mathew P.M. Am. J. Hum. Genet. 56:416-421(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 PRO-147. Ref.11 "Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy." Thomas P., Ye Y., Lightner E. Hum. Mol. Genet. 5:1809-1812(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 PRO-147. Corresponds to variant rs28936678 [ dbSNP \| Ensembl ].	VAR_001557
Natural variantⁱ	254 – 254	1	P → L in HHF2; impairs trafficking of the mutant channel. 1 Publication Manual assertion based on experiment inⁱ Ref.20 "Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity." Tornovsky S., Crane A., Cosgrove K.E., Hussain K., Lavie J., Heyman M., Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O., Nahari E., Potikha T., Zangen D., Tenenbaum-Rakover Y., de Vries L., Argente J., Gracia R., Landau H. Glaser B. J. Clin. Endocrinol. Metab. 89:6224-6234(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 LEU-254, CHARACTERIZATION OF VARIANT HHF2 LEU-254.	VAR_026513
Natural variantⁱ	259 – 259	1	H → R in HHF2; impairs trafficking and abolishes channel function. 1 Publication Manual assertion based on experiment inⁱ Ref.28 "Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function." Marthinet E., Bloc A., Oka Y., Tanizawa Y., Wehrle-Haller B., Bancila V., Dubuis J.-M., Philippe J., Schwitzgebel V.M. J. Clin. Endocrinol. Metab. 90:5401-5406(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 ARG-259, CHARACTERIZATION OF VARIANT HHF2 ARG-259.	VAR_031345
Natural variantⁱ	266 – 266	1	P → L in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.	VAR_031346
Natural variantⁱ	301 – 301	1	R → H in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301. Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031347

Diabetes mellitus, permanent neonatal (PNDM)

[MIM:606176]: A rare form of diabetes distinct from childhood-onset autoimmune diabetes mellitus type 1. It is characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Permanent neonatal diabetes requires lifelong therapy.8 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	35 – 35	1	F → L in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.	VAR_026498
Natural variantⁱ	35 – 35	1	F → V in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.	VAR_026499
Natural variantⁱ	46 – 46	1	H → Y in PNDM; one patient with mild dysmorphic features. 2 Publications Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330. Ref.34 "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers." Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I. J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.	VAR_031332
Natural variantⁱ	50 – 50	1	R → P in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current; one patient with developmental delay. 2 Publications Manual assertion based on experiment inⁱ Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201. Ref.29 "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects." Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M. Diabetes 55:1705-1712(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM GLN-50 AND PRO-50, CHARACTERIZATION OF VARIANTS PNDM GLN-50 AND PRO-50.	VAR_026500
Natural variantⁱ	50 – 50	1	R → Q in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 Publications Manual assertion based on experiment inⁱ Ref.29 "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects." Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M. Diabetes 55:1705-1712(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM GLN-50 AND PRO-50, CHARACTERIZATION OF VARIANTS PNDM GLN-50 AND PRO-50. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031333
Natural variantⁱ	52 – 52	1	Q → R in PNDM; with developmental delay and epilepsy; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201. 2 Publications Manual assertion based on experiment inⁱ Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026501
Natural variantⁱ	53 – 53	1	G → D in PNDM; with developmental delay and epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031334
Natural variantⁱ	53 – 53	1	G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026502
Natural variantⁱ	53 – 53	1	G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026503
Natural variantⁱ	59 – 59	1	V → G in PNDM; with developmental delay and epilepsy; with neurologic features; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201; decreases ATP sensitivity indirectly by favoring the open conformation of the channel. 2 Publications Manual assertion based on experiment inⁱ Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026504
Natural variantⁱ	59 – 59	1	V → M in PNDM; four patients with developmental delay and muscle weakness. 5 Publications Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333. Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330. Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026505
Natural variantⁱ	164 – 164	1	L → P in PNDM. 2 Publications Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330. Ref.34 "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers." Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I. J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.	VAR_031341
Natural variantⁱ	166 – 166	1	C → Y in PNDM; individual also diagnosed with West syndrome. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031342
Natural variantⁱ	170 – 170	1	K → N in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.	VAR_026508
Natural variantⁱ	170 – 170	1	K → R in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.	VAR_026509
Natural variantⁱ	170 – 170	1	K → T in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031343
Natural variantⁱ	201 – 201	1	R → C in PNDM; two individuals with developmental delay; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59. 5 Publications Manual assertion based on experiment inⁱ Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330. Ref.19 "Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel." Gloyn A.L., Cummings E.A., Edghill E.L., Harries L.W., Scott R., Costa T., Temple I.K., Hattersley A.T., Ellard S. J. Clin. Endocrinol. Metab. 89:3932-3935(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PNDM CYS-201. Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026511
Natural variantⁱ	201 – 201	1	R → H in PNDM; ability of ATP to block mutant channels greatly reduced. 5 Publications Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333. Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330. Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330. Ref.34 "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers." Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I. J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.	VAR_026512
Natural variantⁱ	201 – 201	1	R → L in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031344
Natural variantⁱ	296 – 296	1	I → L in PNDM; with developmental delay and epilepsy. 2 Publications Manual assertion based on experiment inⁱ Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026514
Natural variantⁱ	322 – 322	1	E → K in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.	VAR_026515
Natural variantⁱ	330 – 330	1	Y → C in PNDM. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333. Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.	VAR_026516
Natural variantⁱ	330 – 330	1	Y → S in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031348
Natural variantⁱ	333 – 333	1	F → I in PNDM; alters gating characteristics, decreases sensitivity to inhibition by ATP and increases intrinsic open probability. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.	VAR_026517

Transient neonatal diabetes mellitus 3 (TNDM3)

[MIM:610582]: Neonatal diabetes mellitus, defined as insulin-requiring hyperglycemia within the first month of life, is a rare entity. In about half of the neonates, diabetes is transient and resolves at a median age of 3 months, whereas the rest have a permanent form of diabetes. In a significant number of patients with transient neonatal diabetes mellitus, diabetes type 2 appears later in life. The onset and severity of TNDM3 is variable with childhood-onset diabetes, gestational diabetes or adult-onset diabetes described.2 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	42 – 42	1	C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. 1 Publication Manual assertion based on experiment inⁱ Ref.27 "The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus." Yorifuji T., Nagashima K., Kurokawa K., Kawai M., Oishi M., Akazawa Y., Hosokawa M., Yamada Y., Inagaki N., Nakahata T. J. Clin. Endocrinol. Metab. 90:3174-3178(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TNDM3 ARG-42, CHARACTERIZATION OF VARIANT TNDM3 ARG-42.	VAR_031331
Natural variantⁱ	53 – 53	1	G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026502
Natural variantⁱ	53 – 53	1	G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026503
Natural variantⁱ	182 – 182	1	I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026510

Defects in KCNJ11 may contribute to non-insulin-dependent diabetes mellitus (NIDDM), also known as diabetes mellitus type 2.

Keywords - Diseaseⁱ

Diabetes mellitus, Disease mutation

Organism-specific databases

MIMⁱ	601820. phenotype. 606176. phenotype. 610582. phenotype.
Orphanetⁱ	276580. Autosomal dominant hyperinsulinism due to Kir6.2 deficiency. 79644. Autosomal recessive hyperinsulinism due to Kir6.2 deficiency. 79134. DEND syndrome. 276603. Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency. 552. MODY syndrome. 99885. Permanent neonatal diabetes mellitus. 99886. Transient neonatal diabetes mellitus.
PharmGKBⁱ	PA217.

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Chainⁱ	1 – 390	390	ATP-sensitive inward rectifier potassium channel 11		PRO_0000154957	Add BLAST

Amino acid modifications

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Modified residueⁱ	341 – 341	1	Phosphothreonine; by MAPK11 Publication Manual assertion based on experiment inⁱ Ref.9 "Functional modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation." Lin Y.F., Chai Y. Neuroscience 152:371-380(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-341 AND SER-385.
Modified residueⁱ	385 – 385	1	Phosphoserine; by MAPK11 Publication Manual assertion based on experiment inⁱ Ref.9 "Functional modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation." Lin Y.F., Chai Y. Neuroscience 152:371-380(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT THR-341 AND SER-385.

Post-translational modificationⁱ

Phosphorylation by MAPK1 results in changes in channel gating that destabilize the closed states and reduce the ATP sensitivity.1 Publication

Keywords - PTMⁱ

Phosphoprotein

Proteomic databases

PaxDbⁱ	Q14654.
PRIDEⁱ	Q14654.

PTM databases

PhosphoSiteⁱ	Q14654.

PhosphoSiteⁱ

Q14654.

Expressionⁱ

Gene expression databases

Bgeeⁱ	Q14654.
CleanExⁱ	HS_KCNJ11.
ExpressionAtlasⁱ	Q14654. baseline and differential.
Genevestigatorⁱ	Q14654.

Organism-specific databases

HPAⁱ	HPA048891.

Interactionⁱ

Subunit structureⁱ

Interacts with ABCC8/SUR. Interacts with ABCC9/SUR2.2 Publications

Protein-protein interaction databases

DIPⁱ	DIP-58643N.
IntActⁱ	Q14654. 1 interaction.
STRINGⁱ	9606.ENSP00000345708.

Structureⁱ

3D structure databases

ProteinModelPortalⁱ	Q14654.
SMRⁱ	Q14654. Positions 32-356.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Family & Domainsⁱ

Motif

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Motifⁱ	130 – 135	6	Selectivity filterBy similarity

Sequence similaritiesⁱ

Belongs to the inward rectifier-type potassium channel (TC 1.A.2.1) family. KCNJ11 subfamily. [View classification]Curated

Keywords - Domainⁱ

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGⁱ	NOG72812.
HOGENOMⁱ	HOG000237325.
HOVERGENⁱ	HBG006178.
InParanoidⁱ	Q14654.
KOⁱ	K05004.
OrthoDBⁱ	EOG7XPZ5K.
PhylomeDBⁱ	Q14654.
TreeFamⁱ	TF313676.

Family and domain databases

Gene3Dⁱ	2.60.40.1400. 1 hit.
InterProⁱ	IPR014756. Ig_E-set. IPR016449. K_chnl_inward-rec_Kir. IPR003279. K_chnl_inward-rec_Kir6.2. IPR013518. K_chnl_inward-rec_Kir_cyto. [Graphical view]
PANTHERⁱ	PTHR11767. PTHR11767. 1 hit. PTHR11767:SF44. PTHR11767:SF44. 1 hit.
Pfamⁱ	PF01007. IRK. 1 hit. [Graphical view]
PIRSFⁱ	PIRSF005465. GIRK_kir. 1 hit.
PRINTSⁱ	PR01332. KIR62CHANNEL. PR01320. KIRCHANNEL.
SUPFAMⁱ	SSF81296. SSF81296. 1 hit.

Sequences (2)ⁱ

Sequence statusⁱ: Complete.

This entry describes 2 isoformsⁱ produced by alternative splicing. Align

Isoform 1 (identifier: Q14654-1) [UniParc]FASTA Add to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MLSRKGIIPE EYVLTRLAED PAEPRYRARQ RRARFVSKKG NCNVAHKNIR 
        60         70         80         90        100
EQGRFLQDVF TTLVDLKWPH TLLIFTMSFL CSWLLFAMAW WLIAFAHGDL 
       110        120        130        140        150
APSEGTAEPC VTSIHSFSSA FLFSIEVQVT IGFGGRMVTE ECPLAILILI 
       160        170        180        190        200
VQNIVGLMIN AIMLGCIFMK TAQAHRRAET LIFSKHAVIA LRHGRLCFML 
       210        220        230        240        250
RVGDLRKSMI ISATIHMQVV RKTTSPEGEV VPLHQVDIPM ENGVGGNSIF 
       260        270        280        290        300
LVAPLIIYHV IDANSPLYDL APSDLHHHQD LEIIVILEGV VETTGITTQA 
       310        320        330        340        350
RTSYLADEIL WGQRFVPIVA EEDGRYSVDY SKFGNTIKVP TPLCTARQLD 
       360        370        380        390
EDHSLLEALT LASARGPLRK RSVPMAKAKP KFSISPDSLS

Length:390

Mass (Da):43,541

Last modified:September 27, 2005 - v2

Checksum:ⁱ8345E7DBCE897344

GO

Isoform 2 (identifier: Q14654-2) [UniParc]FASTA Add to Basket

The sequence of this isoform differs from the canonical sequence as follows:
1-87: Missing.

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        10         20         30         40         50
MAWWLIAFAH GDLAPSEGTA EPCVTSIHSF SSAFLFSIEV QVTIGFGGRM 
        60         70         80         90        100
VTEECPLAIL ILIVQNIVGL MINAIMLGCI FMKTAQAHRR AETLIFSKHA 
       110        120        130        140        150
VIALRHGRLC FMLRVGDLRK SMIISATIHM QVVRKTTSPE GEVVPLHQVD 
       160        170        180        190        200
IPMENGVGGN SIFLVAPLII YHVIDANSPL YDLAPSDLHH HQDLEIIVIL 
       210        220        230        240        250
EGVVETTGIT TQARTSYLAD EILWGQRFVP IVAEEDGRYS VDYSKFGNTI 
       260        270        280        290        300
KVPTPLCTAR QLDEDHSLLE ALTLASARGP LRKRSVPMAK AKPKFSISPD 

SLS

Show »

Length:303

Mass (Da):33,263

Checksum:ⁱCBB99A32291CD64B

GO

Sequence cautionⁱ

The sequence AAH40617.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Sequence conflictⁱ	370 – 370	1	K → E in BAG63046. (PubMed:14702039)Curated

Natural variant

Feature key	Position(s)	Length	Description	Feature identifier
Natural variantⁱ	10 – 10	1	E → K Rare polymorphism. 1 Publication Manual assertion based on experiment inⁱ Ref.13 "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM." Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A. Diabetes 46:502-507(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337.	VAR_008659
Natural variantⁱ	18 – 18	1	A → G. Corresponds to variant rs41309072 [ dbSNP \| Ensembl ].	VAR_055978
Natural variantⁱ	23 – 23	1	E → K Linked to V-337. 6 Publications Manual assertion based on experiment inⁱ Ref.3 "Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS LYS-23 AND VAL-337. Ref.12 "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro." Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M. Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385. Ref.13 "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM." Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A. Diabetes 46:502-507(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337. Ref.15 "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-23 AND VAL-337. Ref.23 "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy." Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J. Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337. Ref.31 "Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI)." Fernandez-Marmiesse A., Salas A., Vega A., Fernandez-Lorenzo J.R., Barreiro J., Carracedo A. Hum. Mutat. 27:214-214(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-23 AND VAL-337. Corresponds to variant rs5219 [ dbSNP \| Ensembl ].	VAR_008660
Natural variantⁱ	34 – 34	1	R → H in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.23 "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy." Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J. Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337.	VAR_031329
Natural variantⁱ	35 – 35	1	F → L in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.	VAR_026498
Natural variantⁱ	35 – 35	1	F → V in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.	VAR_026499
Natural variantⁱ	40 – 40	1	G → D in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031330
Natural variantⁱ	42 – 42	1	C → R in TNDM3; increased spontaneous open probability; reduced ATP sensitivity; reduced expression at the cell surface of the functional ATP-sensitive form. 1 Publication Manual assertion based on experiment inⁱ Ref.27 "The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus." Yorifuji T., Nagashima K., Kurokawa K., Kawai M., Oishi M., Akazawa Y., Hosokawa M., Yamada Y., Inagaki N., Nakahata T. J. Clin. Endocrinol. Metab. 90:3174-3178(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT TNDM3 ARG-42, CHARACTERIZATION OF VARIANT TNDM3 ARG-42.	VAR_031331
Natural variantⁱ	46 – 46	1	H → Y in PNDM; one patient with mild dysmorphic features. 2 Publications Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330. Ref.34 "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers." Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I. J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.	VAR_031332
Natural variantⁱ	50 – 50	1	R → P in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current; one patient with developmental delay. 2 Publications Manual assertion based on experiment inⁱ Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201. Ref.29 "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects." Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M. Diabetes 55:1705-1712(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM GLN-50 AND PRO-50, CHARACTERIZATION OF VARIANTS PNDM GLN-50 AND PRO-50.	VAR_026500
Natural variantⁱ	50 – 50	1	R → Q in PNDM; decreased inhibition by ATP; enhanced activation by Mg(2+); increased current. 2 Publications Manual assertion based on experiment inⁱ Ref.29 "Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects." Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M. Diabetes 55:1705-1712(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM GLN-50 AND PRO-50, CHARACTERIZATION OF VARIANTS PNDM GLN-50 AND PRO-50. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031333
Natural variantⁱ	52 – 52	1	Q → R in PNDM; with developmental delay and epilepsy; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201. 2 Publications Manual assertion based on experiment inⁱ Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026501
Natural variantⁱ	53 – 53	1	G → D in PNDM; with developmental delay and epilepsy. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031334
Natural variantⁱ	53 – 53	1	G → R in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026502
Natural variantⁱ	53 – 53	1	G → S in TNDM3; also found in a family member with PNDM; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026503
Natural variantⁱ	55 – 55	1	F → L in HHF2; does neither affect channel expression nor channel response to MgADP. 1 Publication Manual assertion based on experiment inⁱ Ref.32 "A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels." Lin Y.-W., MacMullen C., Ganguly A., Stanley C.A., Shyng S.-L. J. Biol. Chem. 281:3006-3012(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 LEU-55, CHARACTERIZATION OF VARIANT HHF2 LEU-55.	VAR_031335
Natural variantⁱ	59 – 59	1	V → G in PNDM; with developmental delay and epilepsy; with neurologic features; produces larger current and more change in ATP sensitivity than mutation associated with mild disease C-201; decreases ATP sensitivity indirectly by favoring the open conformation of the channel. 2 Publications Manual assertion based on experiment inⁱ Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026504
Natural variantⁱ	59 – 59	1	V → M in PNDM; four patients with developmental delay and muscle weakness. 5 Publications Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333. Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330. Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026505
Natural variantⁱ	67 – 67	1	K → N in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.16 "Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism." Huopio H., Jaeaeskelaeinen J., Komulainen J., Miettinen R., Kaerkkaeinen P., Laakso M., Tapanainen P., Voutilainen R., Otonkoski T. J. Clin. Endocrinol. Metab. 87:4502-4507(2002) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 ASN-67.	VAR_026506
Natural variantⁱ	91 – 91	1	W → R in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.14 "Molecular biology of adenosine triphosphate-sensitive potassium channels." Aguilar-Bryan L., Bryan J. Endocr. Rev. 20:101-135(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 ARG-91.	VAR_026507
Natural variantⁱ	101 – 101	1	A → D in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301. Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031336
Natural variantⁱ	116 – 116	1	S → P in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031337
Natural variantⁱ	134 – 134	1	G → A in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.	VAR_031338
Natural variantⁱ	136 – 136	1	R → L in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301. Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031339
Natural variantⁱ	147 – 147	1	L → P in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.10 "Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy." Thomas P.M., Cote G.J., Hallman D.M., Mathew P.M. Am. J. Hum. Genet. 56:416-421(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 PRO-147. Ref.11 "Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy." Thomas P., Ye Y., Lightner E. Hum. Mol. Genet. 5:1809-1812(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 PRO-147. Corresponds to variant rs28936678 [ dbSNP \| Ensembl ].	VAR_001557
Natural variantⁱ	148 – 148	1	I → S.2 Publications Manual assertion based on experiment inⁱ Ref.1 "Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor." Inagaki N., Gonoi T., Clement J.P. IV, Namba N., Inazawa J., Gonzalez G., Aguilar-Bryan L., Seino S., Bryan J. Science 270:1166-1170(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-148. Ref.23 "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy." Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J. Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337.	VAR_031340
Natural variantⁱ	164 – 164	1	L → P in PNDM. 2 Publications Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330. Ref.34 "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers." Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I. J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.	VAR_031341
Natural variantⁱ	166 – 166	1	C → Y in PNDM; individual also diagnosed with West syndrome. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031342
Natural variantⁱ	170 – 170	1	K → N in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.	VAR_026508
Natural variantⁱ	170 – 170	1	K → R in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.	VAR_026509
Natural variantⁱ	170 – 170	1	K → T in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031343
Natural variantⁱ	182 – 182	1	I → V in TNDM3; reduction in the sensitivity to ATP when compared with wild-type. 1 Publication Manual assertion based on experiment inⁱ Ref.24 "Relapsing diabetes can result from moderately activating mutations in KCNJ11." Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T. Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.	VAR_026510
Natural variantⁱ	195 – 195	1	R → H. Corresponds to variant rs5217 [ dbSNP \| Ensembl ].	VAR_014929
Natural variantⁱ	201 – 201	1	R → C in PNDM; two individuals with developmental delay; produces smaller current and less change in ATP sensitivity than mutations associated with severe disease R-52 and G-59. 5 Publications Manual assertion based on experiment inⁱ Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330. Ref.19 "Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel." Gloyn A.L., Cummings E.A., Edghill E.L., Harries L.W., Scott R., Costa T., Temple I.K., Hattersley A.T., Ellard S. J. Clin. Endocrinol. Metab. 89:3932-3935(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT PNDM CYS-201. Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.25 "KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes." The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F. Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026511
Natural variantⁱ	201 – 201	1	R → H in PNDM; ability of ATP to block mutant channels greatly reduced. 5 Publications Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333. Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330. Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330. Ref.34 "Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers." Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I. J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.	VAR_026512
Natural variantⁱ	201 – 201	1	R → L in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031344
Natural variantⁱ	254 – 254	1	P → L in HHF2; impairs trafficking of the mutant channel. 1 Publication Manual assertion based on experiment inⁱ Ref.20 "Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity." Tornovsky S., Crane A., Cosgrove K.E., Hussain K., Lavie J., Heyman M., Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O., Nahari E., Potikha T., Zangen D., Tenenbaum-Rakover Y., de Vries L., Argente J., Gracia R., Landau H. Glaser B. J. Clin. Endocrinol. Metab. 89:6224-6234(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 LEU-254, CHARACTERIZATION OF VARIANT HHF2 LEU-254.	VAR_026513
Natural variantⁱ	259 – 259	1	H → R in HHF2; impairs trafficking and abolishes channel function. 1 Publication Manual assertion based on experiment inⁱ Ref.28 "Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function." Marthinet E., Bloc A., Oka Y., Tanizawa Y., Wehrle-Haller B., Bancila V., Dubuis J.-M., Philippe J., Schwitzgebel V.M. J. Clin. Endocrinol. Metab. 90:5401-5406(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 ARG-259, CHARACTERIZATION OF VARIANT HHF2 ARG-259.	VAR_031345
Natural variantⁱ	266 – 266	1	P → L in HHF2. 1 Publication Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.	VAR_031346
Natural variantⁱ	270 – 270	1	L → V.2 Publications Manual assertion based on experiment inⁱ Ref.12 "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro." Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M. Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385. Ref.13 "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM." Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A. Diabetes 46:502-507(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337. Corresponds to variant rs1800467 [ dbSNP \| Ensembl ].	VAR_008661
Natural variantⁱ	296 – 296	1	I → L in PNDM; with developmental delay and epilepsy. 2 Publications Manual assertion based on experiment inⁱ Ref.21 "Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes." Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H. Hattersley A.T. N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201. Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_026514
Natural variantⁱ	301 – 301	1	R → H in HHF2. 2 Publications Manual assertion based on experiment inⁱ Ref.26 "Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes." Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A. J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301. Ref.33 "Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism." Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A. Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.	VAR_031347
Natural variantⁱ	322 – 322	1	E → K in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.	VAR_026515
Natural variantⁱ	330 – 330	1	Y → C in PNDM. 2 Publications Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333. Ref.18 "Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients." Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M. Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.	VAR_026516
Natural variantⁱ	330 – 330	1	Y → S in PNDM. 1 Publication Manual assertion based on experiment inⁱ Ref.30 "Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype." Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T. Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.	VAR_031348
Natural variantⁱ	333 – 333	1	F → I in PNDM; alters gating characteristics, decreases sensitivity to inhibition by ATP and increases intrinsic open probability. 1 Publication Manual assertion based on experiment inⁱ Ref.17 "Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy." Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R. Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.	VAR_026517
Natural variantⁱ	337 – 337	1	I → V Linked to K-23. 6 Publications Manual assertion based on experiment inⁱ Ref.3 "Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS LYS-23 AND VAL-337. Ref.12 "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro." Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M. Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385. Ref.13 "Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM." Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A. Diabetes 46:502-507(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337. Ref.15 "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-23 AND VAL-337. Ref.23 "Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy." Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J. Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337. Ref.31 "Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI)." Fernandez-Marmiesse A., Salas A., Vega A., Fernandez-Lorenzo J.R., Barreiro J., Carracedo A. Hum. Mutat. 27:214-214(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LYS-23 AND VAL-337. Corresponds to variant rs5215 [ dbSNP \| Ensembl ].	VAR_008662
Natural variantⁱ	355 – 355	1	L → P in NIDDM; Afro-Caribbean. 1 Publication Manual assertion based on experiment inⁱ Ref.12 "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro." Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M. Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385.	VAR_008663
Natural variantⁱ	380 – 380	1	P → PKP in NIDDM.	VAR_008664
Natural variantⁱ	385 – 385	1	S → C.1 Publication Manual assertion based on experiment inⁱ Ref.12 "Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro." Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M. Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385. Corresponds to variant rs41282930 [ dbSNP \| Ensembl ].	VAR_008665

Alternative sequence

Feature key	Position(s)	Length	Description	Graphical view	Feature identifier	Actions
Alternative sequenceⁱ	1 – 87	87	Missing in isoform 2. 2 Publications Manual assertion based on opinion inⁱ Ref.2 "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Ref.4 "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).		VSP_045270	Add BLAST

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	D50582 Genomic DNA. Translation: BAA09131.1. AK301550 mRNA. Translation: BAG63046.1. AC124798 Genomic DNA. No translation available. BC064497 mRNA. Translation: AAH64497.1. BC040617 mRNA. Translation: AAH40617.1. Different initiation. BC112358 mRNA. Translation: AAI12359.1.
CCDSⁱ	CCDS31436.1. [Q14654-1] CCDS53606.1. [Q14654-2]
PIRⁱ	A57616.
RefSeqⁱ	NP_001159762.1. NM_001166290.1.
UniGeneⁱ	Hs.248141.

Genome annotation databases

Ensemblⁱ	ENST00000339994; ENSP00000345708; ENSG00000187486. ENST00000528731; ENSP00000434755; ENSG00000187486.
GeneIDⁱ	3767.
KEGGⁱ	hsa:3767.

Polymorphism databases

DMDMⁱ	76803775.

DMDMⁱ

76803775.

Keywords - Coding sequence diversityⁱ

Alternative splicing, Polymorphism

Cross-referencesⁱ

Sequence databases

Select the link destinations: EMBLⁱ GenBankⁱ DDBJⁱ Links Updated	D50582 Genomic DNA. Translation: BAA09131.1 . AK301550 mRNA. Translation: BAG63046.1 . AC124798 Genomic DNA. No translation available. BC064497 mRNA. Translation: AAH64497.1 . BC040617 mRNA. Translation: AAH40617.1 . Different initiation. BC112358 mRNA. Translation: AAI12359.1 .
CCDSⁱ	CCDS31436.1. [Q14654-1 ] CCDS53606.1. [Q14654-2 ]
PIRⁱ	A57616.
RefSeqⁱ	NP_001159762.1. NM_001166290.1.
UniGeneⁱ	Hs.248141.

3D structure databases

ProteinModelPortalⁱ	Q14654.
SMRⁱ	Q14654. Positions 32-356.
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Protein-protein interaction databases

DIPⁱ	DIP-58643N.
IntActⁱ	Q14654. 1 interaction.
STRINGⁱ	9606.ENSP00000345708.

Chemistry

BindingDBⁱ	Q14654.
ChEMBLⁱ	CHEMBL2095198.
DrugBankⁱ	DB01119. Diazoxide. DB00222. Glimepiride. DB01016. Glyburide. DB00308. Ibutilide. DB00922. Levosimendan. DB01154. Thiamylal. DB00661. Verapamil. DB01392. Yohimbine.
GuidetoPHARMACOLOGYⁱ	442.

PTM databases

PhosphoSiteⁱ	Q14654.

PhosphoSiteⁱ

Q14654.

Polymorphism databases

DMDMⁱ	76803775.

DMDMⁱ

76803775.

Proteomic databases

PaxDbⁱ	Q14654.
PRIDEⁱ	Q14654.

Protocols and materials databases

Structural Biology Knowledgebase	Search...

Structural Biology Knowledgebase

Search...

Genome annotation databases

Ensemblⁱ	ENST00000339994 ; ENSP00000345708 ; ENSG00000187486 . ENST00000528731 ; ENSP00000434755 ; ENSG00000187486 .
GeneIDⁱ	3767.
KEGGⁱ	hsa:3767.

Organism-specific databases

CTDⁱ	3767.
GeneCardsⁱ	GC11M017406.
GeneReviewsⁱ	KCNJ11.
H-InvDB	HIX0035982.
HGNCⁱ	HGNC:6257. KCNJ11.
HPAⁱ	HPA048891.
MIMⁱ	600937. gene. 601820. phenotype. 606176. phenotype. 610582. phenotype.
neXtProtⁱ	NX_Q14654.
Orphanetⁱ	276580. Autosomal dominant hyperinsulinism due to Kir6.2 deficiency. 79644. Autosomal recessive hyperinsulinism due to Kir6.2 deficiency. 79134. DEND syndrome. 276603. Diazoxide-resistant focal hyperinsulinism due to Kir6.2 deficiency. 552. MODY syndrome. 99885. Permanent neonatal diabetes mellitus. 99886. Transient neonatal diabetes mellitus.
PharmGKBⁱ	PA217.
GenAtlasⁱ	Search...

Phylogenomic databases

eggNOGⁱ	NOG72812.
HOGENOMⁱ	HOG000237325.
HOVERGENⁱ	HBG006178.
InParanoidⁱ	Q14654.
KOⁱ	K05004.
OrthoDBⁱ	EOG7XPZ5K.
PhylomeDBⁱ	Q14654.
TreeFamⁱ	TF313676.

Enzyme and pathway databases

Reactomeⁱ	REACT_18325. Regulation of insulin secretion. REACT_75775. ATP sensitive Potassium channels.
SignaLinkⁱ	Q14654.

Miscellaneous databases

GeneWikiⁱ	Kir6.2.
GenomeRNAiⁱ	3767.
NextBioⁱ	14771.
PROⁱ	Q14654.
SOURCEⁱ	Search...

Gene expression databases

Bgeeⁱ	Q14654.
CleanExⁱ	HS_KCNJ11.
ExpressionAtlasⁱ	Q14654. baseline and differential.
Genevestigatorⁱ	Q14654.

Family and domain databases

Gene3Dⁱ	2.60.40.1400. 1 hit.
InterProⁱ	IPR014756. Ig_E-set. IPR016449. K_chnl_inward-rec_Kir. IPR003279. K_chnl_inward-rec_Kir6.2. IPR013518. K_chnl_inward-rec_Kir_cyto. [Graphical view ]
PANTHERⁱ	PTHR11767. PTHR11767. 1 hit. PTHR11767:SF44. PTHR11767:SF44. 1 hit.
Pfamⁱ	PF01007. IRK. 1 hit. [Graphical view ]
PIRSFⁱ	PIRSF005465. GIRK_kir. 1 hit.
PRINTSⁱ	PR01332. KIR62CHANNEL. PR01320. KIRCHANNEL.
SUPFAMⁱ	SSF81296. SSF81296. 1 hit.
ProtoNetⁱ	Search...

Publicationsⁱ

« Hide 'large scale' publications

"Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor."
Inagaki N., Gonoi T., Clement J.P. IV, Namba N., Inazawa J., Gonzalez G., Aguilar-Bryan L., Seino S., Bryan J.
Science 270:1166-1170(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT SER-148.
Tissue: Placenta.
"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Mammary gland.
"Human chromosome 11 DNA sequence and analysis including novel gene identification."
Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.
Sakaki Y.
Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANTS LYS-23 AND VAL-337.
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Tissue: Ovary and Spleen.
"Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells."
Babenko A.P., Gonzalez G., Aguilar-Bryan L., Bryan J.
Circ. Res. 83:1132-1143(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH ABCC9.
"Molecular basis for Kir6.2 channel inhibition by adenine nucleotides."
Ribalet B., John S.A., Weiss J.N.
Biophys. J. 84:266-276(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: MOLECULAR BASIS OF ATP SENSITIVITY.
"Congenital hyperinsulinism: molecular basis of a heterogeneous disease."
Meissner T., Beinbrech B., Mayatepek E.
Hum. Mutat. 13:351-361(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON VARIANTS.
"A mutation in the ATP-binding site of the Kir6.2 subunit of the KATP channel alters coupling with the SUR2A subunit."
Tammaro P., Ashcroft F.M.
J. Physiol. (Lond.) 584:743-753(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CHARACTERIZATION OF VARIANT PNDM ILE-333, INTERACTION WITH ABCC9.
"Functional modulation of the ATP-sensitive potassium channel by extracellular signal-regulated kinase-mediated phosphorylation."
Lin Y.F., Chai Y.
Neuroscience 152:371-380(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-341 AND SER-385.
"Homozygosity mapping, to chromosome 11p, of the gene for familial persistent hyperinsulinemic hypoglycemia of infancy."
Thomas P.M., Cote G.J., Hallman D.M., Mathew P.M.
Am. J. Hum. Genet. 56:416-421(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 PRO-147.
"Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy."
Thomas P., Ye Y., Lightner E.
Hum. Mol. Genet. 5:1809-1812(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 PRO-147.
"Sequence variations in the human Kir6.2 gene, a subunit of the beta-cell ATP-sensitive K-channel: no association with NIDDM in white Caucasian subjects or evidence of abnormal function when expressed in vitro."
Sakura H., Wat N., Horton V., Millns H., Turner R.C., Ashcroft F.M.
Diabetologia 39:1233-1236(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NIDDM PRO-355 AND LYS-PRO-380 INS, VARIANTS LYS-23; VAL-270; VAL-337 AND CYS-385.
"Sequence variants in the pancreatic islet beta-cell inwardly rectifying K+ channel Kir6.2 (Bir) gene: identification and lack of role in Caucasian patients with NIDDM."
Inoue H., Ferrer J., Warren-Perry M., Zhang Y., Millns H., Turner R.C., Elbein S.C., Hampe C.L., Suarez B.K., Inagaki N., Seino S., Permutt M.A.
Diabetes 46:502-507(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-10; LYS-23; VAL-270 AND VAL-337.
"Molecular biology of adenosine triphosphate-sensitive potassium channels."
Aguilar-Bryan L., Bryan J.
Endocr. Rev. 20:101-135(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 ARG-91.
"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis."
Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A.
Nat. Genet. 22:239-247(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-23 AND VAL-337.
"Acute insulin response tests for the differential diagnosis of congenital hyperinsulinism."
Huopio H., Jaeaeskelaeinen J., Komulainen J., Miettinen R., Kaerkkaeinen P., Laakso M., Tapanainen P., Voutilainen R., Otonkoski T.
J. Clin. Endocrinol. Metab. 87:4502-4507(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 ASN-67.
"Permanent neonatal diabetes due to mutations in KCNJ11 encoding Kir6.2: patient characteristics and initial response to sulfonylurea therapy."
Sagen J.V., Raeder H., Hathout E., Shehadeh N., Gudmundsson K., Baevre H., Abuelo D., Phornphutkul C., Molnes J., Bell G.I., Gloyn A.L., Hattersley A.T., Molven A., Soevik O., Njoelstad P.R.
Diabetes 53:2713-2718(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM VAL-35; MET-59; HIS-201; CYS-330 AND ILE-333.
"Kir6.2 mutations are a common cause of permanent neonatal diabetes in a large cohort of French patients."
Vaxillaire M., Populaire C., Busiah K., Cave H., Gloyn A.L., Hattersley A.T., Czernichow P., Froguel P., Polak M.
Diabetes 53:2719-2722(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM LEU-35; MET-59; CYS-201; HIS-201; LYS-322 AND CYS-330.
"Permanent neonatal diabetes due to paternal germline mosaicism for an activating mutation of the KCNJ11 gene encoding the Kir6.2 subunit of the beta-cell potassium adenosine triphosphate channel."
Gloyn A.L., Cummings E.A., Edghill E.L., Harries L.W., Scott R., Costa T., Temple I.K., Hattersley A.T., Ellard S.
J. Clin. Endocrinol. Metab. 89:3932-3935(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT PNDM CYS-201.
"Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity."
Tornovsky S., Crane A., Cosgrove K.E., Hussain K., Lavie J., Heyman M., Nesher Y., Kuchinski N., Ben-Shushan E., Shatz O., Nahari E., Potikha T., Zangen D., Tenenbaum-Rakover Y., de Vries L., Argente J., Gracia R., Landau H.
Glaser B.
J. Clin. Endocrinol. Metab. 89:6224-6234(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 LEU-254, CHARACTERIZATION OF VARIANT HHF2 LEU-254.
"Activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 and permanent neonatal diabetes."
Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H.
Hattersley A.T.
N. Engl. J. Med. 350:1838-1849(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM ARG-52; GLY-59; MET-59; HIS-201; CYS-201 AND LEU-296, CHARACTERIZATION OF VARIANT PNDM HIS-201.
Erratum
Gloyn A.L., Pearson E.R., Antcliff J.F., Proks P., Bruining G.J., Slingerland A.S., Howard N., Srinivasan S., Silva J.M.C.L., Molnes J., Edghill E.L., Frayling T.M., Temple I.K., Mackay D., Shield J.P.H., Sumnik Z., van Rhijn A., Wales J.K.H.
Hattersley A.T.
N. Engl. J. Med. 351:1470-1470(2004)
"Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features."
Proks P., Antcliff J.F., Lippiat J., Gloyn A.L., Hattersley A.T., Ashcroft F.M.
Proc. Natl. Acad. Sci. U.S.A. 101:17539-17544(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS PNDM ARG-52; GLY-59 AND CYS-201.
"Genotypes of the pancreatic beta-cell K-ATP channel and clinical phenotypes of Japanese patients with persistent hyperinsulinaemic hypoglycaemia of infancy."
Ohkubo K., Nagashima M., Naito Y., Taguchi T., Suita S., Okamoto N., Fujinaga H., Tsumura K., Kikuchi K., Ono J.
Clin. Endocrinol. (Oxf.) 62:458-465(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 HIS-34, VARIANTS LYS-23; SER-148 AND VAL-337.
"Relapsing diabetes can result from moderately activating mutations in KCNJ11."
Gloyn A.L., Reimann F., Girard C., Edghill E.L., Proks P., Pearson E.R., Temple I.K., Mackay D.J.G., Shield J.P.H., Freedenberg D., Noyes K., Ellard S., Ashcroft F.M., Gribble F.M., Hattersley A.T.
Hum. Mol. Genet. 14:925-934(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182, CHARACTERIZATION OF VARIANTS TNDM3 SER-53; ARG-53 AND VAL-182.
"KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes."
The early onset diabetes study group of the Italian society of pediatric endocrinology and diabetes
Massa O., Iafusco D., D'Amato E., Gloyn A.L., Hattersley A.T., Pasquino B., Tonini G., Dammacco F., Zanette G., Meschi F., Porzio O., Bottazzo G., Crino A., Lorini R., Cerutti F., Vanelli M., Barbetti F.
Hum. Mutat. 25:22-27(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM PRO-50; MET-59; ARG-170; ASN-170 AND CYS-201.
"Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes."
Henwood M.J., Kelly A., MacMullen C., Bhatia P., Ganguly A., Thornton P.S., Stanley C.A.
J. Clin. Endocrinol. Metab. 90:789-794(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHF2 ASP-101; ALA-134; LEU-136; LEU-266 AND HIS-301.
"The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus."
Yorifuji T., Nagashima K., Kurokawa K., Kawai M., Oishi M., Akazawa Y., Hosokawa M., Yamada Y., Inagaki N., Nakahata T.
J. Clin. Endocrinol. Metab. 90:3174-3178(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TNDM3 ARG-42, CHARACTERIZATION OF VARIANT TNDM3 ARG-42.
"Severe congenital hyperinsulinism caused by a mutation in the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium channel impairing trafficking and function."
Marthinet E., Bloc A., Oka Y., Tanizawa Y., Wehrle-Haller B., Bancila V., Dubuis J.-M., Philippe J., Schwitzgebel V.M.
J. Clin. Endocrinol. Metab. 90:5401-5406(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 ARG-259, CHARACTERIZATION OF VARIANT HHF2 ARG-259.
"Mutations at the same residue (R50) of Kir6.2 (KCNJ11) that cause neonatal diabetes produce different functional effects."
Shimomura K., Girard C.A.J., Proks P., Nazim J., Lippiat J.D., Cerutti F., Lorini R., Ellard S., Hattersely A.T., Barbetti F., Ashcroft F.M.
Diabetes 55:1705-1712(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM GLN-50 AND PRO-50, CHARACTERIZATION OF VARIANTS PNDM GLN-50 AND PRO-50.
"Mutations in KCNJ11, which encodes Kir6.2, are a common cause of diabetes diagnosed in the first 6 months of life, with the phenotype determined by genotype."
Flanagan S.E., Edghill E.L., Gloyn A.L., Ellard S., Hattersley A.T.
Diabetologia 49:1190-1197(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM TYR-46; GLN-50; ARG-52; ASP-53; GLY-59; MET-59; PRO-164; TYR-166; THR-170; CYS-201; HIS-201; LEU-201; LEU-296 AND SER-330.
"Mutation spectra of ABCC8 gene in Spanish patients with Hyperinsulinism of Infancy (HI)."
Fernandez-Marmiesse A., Salas A., Vega A., Fernandez-Lorenzo J.R., Barreiro J., Carracedo A.
Hum. Mutat. 27:214-214(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LYS-23 AND VAL-337.
"A novel KCNJ11 mutation associated with congenital hyperinsulinism reduces the intrinsic open probability of beta-cell ATP-sensitive potassium channels."
Lin Y.-W., MacMullen C., Ganguly A., Stanley C.A., Shyng S.-L.
J. Biol. Chem. 281:3006-3012(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HHF2 LEU-55, CHARACTERIZATION OF VARIANT HHF2 LEU-55.
"Molecular and immunohistochemical analyses of the focal form of congenital hyperinsulinism."
Suchi M., MacMullen C.M., Thornton P.S., Adzick N.S., Ganguly A., Ruchelli E.D., Stanley C.A.
Mod. Pathol. 19:122-129(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS HHF2 ASP-40; ASP-101; PRO-116; LEU-136 AND HIS-301.
"Prevalence of permanent neonatal diabetes in Slovakia and successful replacement of insulin with sulfonylurea therapy in KCNJ11 and ABCC8 mutation carriers."
Stanik J., Gasperikova D., Paskova M., Barak L., Javorkova J., Jancova E., Ciljakova M., Hlava P., Michalek J., Flanagan S.E., Pearson E., Hattersley A.T., Ellard S., Klimes I.
J. Clin. Endocrinol. Metab. 92:1276-1282(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PNDM TYR-46; PRO-164 AND HIS-201.

+Additional computationally mapped references.

Entry informationⁱ

Entry nameⁱ

KCJ11_HUMAN

Accessionⁱ

Primary (citable) accession number: Q14654
Secondary accession number(s): B4DWI4

Q8IW96

Entry historyⁱ

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	September 27, 2005
Last modified:	January 7, 2015
This is version 160 of the entry and version 2 of the sequence. [Complete history]

Entry statusⁱ

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousⁱ

Keywords - Technical termⁱ

Complete proteome, Reference proteome

Documents

Human chromosome 11
Human chromosome 11: entries, gene names and cross-references to MIM
Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations
Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations
MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
SIMILARITY comments
Index of protein domains and families

External Data

Dasty 3

Similar proteinsⁱ

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:

100%	UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%	UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%	UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Supporting data

Q14654

- KCJ11_HUMAN

UniProt

Q14654 - KCJ11_HUMAN

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ATP-sensitive inward rectifier potassium channel 11

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<p>Provides any useful information about the protein, mostly biological knowledge.</p><p><a href='../manual/function_section' target='_top'>More...</a></p>Functioni

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<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:</p><p><a href='../manual/gene_ontology' target='_top'>More...</a></p>GO - Biological processi

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Functionⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Sequences (2)ⁱ

Sequence cautionⁱ

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Publicationsⁱ

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Miscellaneousⁱ