Identification of mutations in SLC24A4, encoding a potassium-dependent sodium/calcium exchanger, as a cause of amelogenesis imperfecta

Am J Hum Genet. 2013 Feb 7;92(2):307-12. doi: 10.1016/j.ajhg.2013.01.003. Epub 2013 Jan 31.


A combination of autozygosity mapping and exome sequencing identified a null mutation in SLC24A4 in a family with hypomineralized amelogenesis imperfect a (AI), a condition in which tooth enamel formation fails. SLC24A4 encodes a calcium transporter upregulated in ameloblasts during the maturation stage of amelogenesis. Screening of further AI families identified a missense mutation in the ion-binding site of SLC24A4 expected to severely diminish or abolish the ion transport function of the protein. Furthermore, examination of previously generated Slc24a4 null mice identified a severe defect in tooth enamel that reflects impaired amelogenesis. These findings support a key role for SLC24A4 in calcium transport during enamel formation.

Publication types

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

MeSH terms

  • Amelogenesis Imperfecta / genetics*
  • Amino Acid Sequence
  • Animals
  • Antiporters / chemistry
  • Antiporters / genetics*
  • Base Sequence
  • Family
  • Female
  • Humans
  • Incisor / ultrastructure
  • Male
  • Mice
  • Mice, Knockout
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Phenotype
  • Sodium-Calcium Exchanger / genetics*


  • Antiporters
  • SLC24A4 protein, human
  • Slc24a4 protein, mouse
  • Sodium-Calcium Exchanger
  • potassium-dependent sodium-calcium exchanger