Familial distal renal tubular acidosis is associated with mutations in the red cell anion exchanger (Band 3, AE1) gene

J Clin Invest. 1997 Oct 1;100(7):1693-707. doi: 10.1172/JCI119694.


All affected patients in four families with autosomal dominant familial renal tubular acidosis (dRTA) were heterozygous for mutations in their red cell HCO3-/Cl- exchanger, band 3 (AE1, SLC4A1) genes, and these mutations were not found in any of the nine normal family members studied. The mutation Arg589--> His was present in two families, while Arg589--> Cys and Ser613--> Phe changes were found in the other families. Linkage studies confirmed the co-segregation of the disease with a genetic marker close to AE1. The affected individuals with the Arg589 mutations had reduced red cell sulfate transport and altered glycosylation of the red cell band 3 N-glycan chain. The red cells of individuals with the Ser613--> Phe mutation had markedly increased red cell sulfate transport but almost normal red cell iodide transport. The erythroid and kidney isoforms of the mutant band 3 proteins were expressed in Xenopus oocytes and all showed significant chloride transport activity. We conclude that dominantly inherited dRTA is associated with mutations in band 3; but both the disease and its autosomal dominant inheritance are not related simply to the anion transport activity of the mutant proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / metabolism
  • Acidosis, Renal Tubular / genetics*
  • Adult
  • Amino Acid Sequence
  • Anion Exchange Protein 1, Erythrocyte / genetics*
  • Anion Exchange Protein 1, Erythrocyte / metabolism
  • Anions / metabolism
  • Arginine / genetics
  • Biological Transport
  • Child
  • Child, Preschool
  • Erythrocytes, Abnormal / physiology*
  • Female
  • Genetic Linkage
  • Glycosylation
  • Humans
  • Iodides / metabolism
  • Male
  • Middle Aged
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Polymorphism, Single-Stranded Conformational
  • Recombinant Proteins / biosynthesis
  • Sequence Analysis, DNA
  • Serine / genetics
  • Sulfates / metabolism


  • Anion Exchange Protein 1, Erythrocyte
  • Anions
  • Iodides
  • Recombinant Proteins
  • Sulfates
  • Serine
  • Arginine
  • 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid