Recurrent ATP1A1 variant Gly903Arg causes developmental delay, intellectual disability, and autism

Ann Clin Transl Neurol. 2024 Apr;11(4):1075-1079. doi: 10.1002/acn3.51963. Epub 2024 Mar 19.


ATP1A1 encodes a sodium-potassium ATPase that has been linked to several neurological diseases. Using exome and genome sequencing, we identified the heterozygous ATP1A1 variant NM_000701.8: c.2707G>A;p.(Gly903Arg) in two unrelated children presenting with delayed motor and speech development and autism. While absent in controls, the variant occurred de novo in one proband and co-segregated in two affected half-siblings, with mosaicism in the healthy mother. Using a specific ouabain resistance assay in mutant transfected HEK cells, we found significantly reduced cell viability. Demonstrating loss of ATPase function, we conclude that this novel variant is pathogenic, expanding the phenotype spectrum of ATP1A1.

Publication types

  • Case Reports

MeSH terms

  • Adenosine Triphosphatases
  • Autistic Disorder* / genetics
  • Child
  • Family
  • Humans
  • Intellectual Disability* / genetics
  • Siblings
  • Sodium-Potassium-Exchanging ATPase / genetics


  • Adenosine Triphosphatases
  • ATP1A1 protein, human
  • Sodium-Potassium-Exchanging ATPase