Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated with familial hemiplegic migraine type 2

Nat Genet. 2003 Feb;33(2):192-6. doi: 10.1038/ng1081. Epub 2003 Jan 21.


Headache attacks and autonomic dysfunctions characterize migraine, a very common, disabling disorder with a prevalence of 12% in the general population of Western countries. About 20% of individuals affected with migraine experience aura, a visual or sensory-motor neurological dysfunction that usually precedes or accompanies the headache. Although the mode of transmission is controversial, population-based and twin studies have implicated genetic factors, especially in migraine with aura. Familial hemiplegic migraine is a hereditary form of migraine characterized by aura and some hemiparesis. Here we show that mutations in the gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM 602481). Functional data indicate that the putative pathogenetic mechanism is triggered by a loss of function of a single allele of ATP1A2. This is the first report associating mutations of Na+K+ pump subunits to genetic diseases.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • COS Cells
  • Calcium Channels / genetics
  • Case-Control Studies
  • Cell Survival / drug effects
  • Chlorocebus aethiops
  • Chromatography, High Pressure Liquid
  • Chromosomes, Human, Pair 1 / genetics
  • Drug Resistance
  • Enzyme Inhibitors / pharmacology
  • Female
  • Haploidy
  • HeLa Cells
  • Humans
  • Male
  • Migraine with Aura / enzymology*
  • Migraine with Aura / genetics*
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Mutation*
  • Ouabain / pharmacology
  • Pedigree
  • Peptide Fragments
  • Sodium-Potassium-Exchanging ATPase / genetics*
  • Sodium-Potassium-Exchanging ATPase / metabolism
  • Transfection


  • Calcium Channels
  • Enzyme Inhibitors
  • Peptide Fragments
  • Ouabain
  • ATP1A2 protein, human
  • Sodium-Potassium-Exchanging ATPase

Associated data

  • OMIM/141500
  • OMIM/602481
  • RefSeq/NM_001678