Update of variants identified in the pancreatic β-cell KATP channel genes KCNJ11 and ABCC8 in individuals with congenital hyperinsulinism and diabetes

Hum Mutat. 2020 May;41(5):884-905. doi: 10.1002/humu.23995. Epub 2020 Feb 17.


The most common genetic cause of neonatal diabetes and hyperinsulinism is pathogenic variants in ABCC8 and KCNJ11. These genes encode the subunits of the β-cell ATP-sensitive potassium channel, a key component of the glucose-stimulated insulin secretion pathway. Mutations in the two genes cause dysregulated insulin secretion; inactivating mutations cause an oversecretion of insulin, leading to congenital hyperinsulinism, whereas activating mutations cause the opposing phenotype, diabetes. This review focuses on variants identified in ABCC8 and KCNJ11, the phenotypic spectrum and the treatment implications for individuals with pathogenic variants.

Keywords: ABCC8; K-ATP channel; KCNJ11; congenital hyperinsulinism; neonatal diabetes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Congenital Hyperinsulinism / diagnosis
  • Congenital Hyperinsulinism / genetics*
  • Diabetes Mellitus / diagnosis
  • Diabetes Mellitus / genetics*
  • Gain of Function Mutation
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Infant, Newborn
  • Insulin-Secreting Cells / metabolism*
  • Loss of Function Mutation
  • Mutation*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Sulfonylurea Receptors / genetics*


  • ABCC8 protein, human
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Sulfonylurea Receptors