Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement

Am J Hum Genet. 2006 Nov;79(5):949-57. doi: 10.1086/508617. Epub 2006 Sep 19.


Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Animals
  • Cell Line
  • Child
  • Child, Preschool
  • Chromosome Mapping
  • Chromosomes, Human, Pair 1 / genetics
  • Claudins
  • Dogs
  • Eye Abnormalities / genetics*
  • Female
  • Humans
  • Kidney / metabolism
  • Kidney Failure, Chronic / genetics*
  • Magnesium Deficiency / genetics*
  • Male
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics*
  • Membrane Proteins / metabolism
  • Mice
  • Middle Aged
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Pedigree
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Tight Junctions / genetics*


  • CLDN19 protein, human
  • Claudins
  • Cldn19 protein, mouse
  • Membrane Proteins
  • Recombinant Proteins
  • claudin 16

Associated data

  • GENBANK/BC115827
  • OMIM/248250
  • RefSeq/NM_053241