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We identified a novel heterozygous mutation, W68R, in the Kir6.2 subunit of the ATP-sensitive potassium (KATP) channel, in a patient with transient neonatal diabetes. This tryptophan is absolutely conserved in mammalian Kir channels. The functional effects of mutations at residue 68 of Kir6.2 were studied by heterologous expression in Xenopus oocytes, and by homology modelling. We found the Kir6.2-W68R mutation causes a small reduction in ATP inhibition in the heterozygous state and an increase in the whole-cell KATP current. This can explain the clinical phenotype of the patient. The effect of the mutation was not charge or size dependent, the order of potency for ATP inhibition being W

Original publication

DOI

10.1113/jphysiol.2011.209700

Type

Journal article

Journal

J Physiol

Publication Date

01/07/2011

Volume

589

Pages

3071 - 3083

Keywords

ATP-Binding Cassette Transporters, Amino Acid Sequence, Animals, Cell Membrane, Child, Conserved Sequence, Diabetes Mellitus, Female, Genetic Carrier Screening, Humans, Infant, Newborn, Infant, Newborn, Diseases, Molecular Sequence Data, Mutation, Oocytes, Phenotype, Potassium Channels, Inwardly Rectifying, Rats, Receptors, Drug, Sulfonylurea Receptors, Tryptophan, Xenopus laevis