Mutations in TMPRSS6 cause iron-refractory iron deficiency anemia (IRIDA)

Nat Genet. 2008 May;40(5):569-71. doi: 10.1038/ng.130. Epub 2008 Apr 13.


Iron deficiency is usually attributed to chronic blood loss or inadequate dietary intake. Here, we show that iron deficiency anemia refractory to oral iron therapy can be caused by germline mutations in TMPRSS6, which encodes a type II transmembrane serine protease produced by the liver that regulates the expression of the systemic iron regulatory hormone hepcidin. These findings demonstrate that TMPRSS6 is essential for normal systemic iron homeostasis in humans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Anemia, Iron-Deficiency / drug therapy
  • Anemia, Iron-Deficiency / genetics*
  • Anemia, Iron-Deficiency / metabolism
  • Child
  • Child, Preschool
  • Female
  • Germ-Line Mutation*
  • Homeostasis / genetics
  • Humans
  • Infant
  • Iron / metabolism*
  • Iron / therapeutic use
  • Male
  • Membrane Proteins / genetics*
  • Protein Structure, Tertiary / genetics
  • Serine Endopeptidases / genetics*


  • Membrane Proteins
  • Iron
  • Serine Endopeptidases
  • TMPRSS6 protein, human