A loss-of-function mutation in NaPi-IIa and renal Fanconi's syndrome

N Engl J Med. 2010 Mar 25;362(12):1102-9. doi: 10.1056/NEJMoa0905647.


We describe two siblings from a consanguineous family with autosomal recessive Fanconi's syndrome and hypophosphatemic rickets. Genetic analysis revealed a homozygous in-frame duplication of 21 bp in SLC34A1, which encodes the renal sodium-inorganic phosphate cotransporter NaPi-IIa, as the causative mutation. Functional studies in Xenopus laevis oocytes and in opossum kidney cells indicated complete loss of function of the mutant NaPi-IIa, resulting from failure of the transporter to reach the plasma membrane. These findings show that disruption of the human NaPi-IIa profoundly impairs overall renal phosphate reabsorption and proximal-tubule function and provide evidence of the critical role of NaPi-IIa in human renal phosphate handling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Calcitriol / blood
  • Cells, Cultured
  • Consanguinity
  • DNA Mutational Analysis
  • Familial Hypophosphatemic Rickets / genetics*
  • Fanconi Syndrome / genetics*
  • Female
  • Genes, Recessive
  • Humans
  • Kidney / cytology
  • Kidney / metabolism
  • Male
  • Mutation
  • Oocytes / metabolism
  • Opossums
  • Pedigree
  • Siblings
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / genetics*
  • Sodium-Phosphate Cotransporter Proteins, Type IIa / metabolism
  • Xenopus laevis


  • SLC34A1 protein, human
  • Sodium-Phosphate Cotransporter Proteins, Type IIa
  • Calcitriol