Mutations in TJP2 cause progressive cholestatic liver disease

Nat Genet. 2014 Apr;46(4):326-8. doi: 10.1038/ng.2918. Epub 2014 Mar 9.


Elucidating genetic causes of cholestasis has proved to be important in understanding the physiology and pathophysiology of the liver. Here we show that protein-truncating mutations in the tight junction protein 2 gene (TJP2) cause failure of protein localization and disruption of tight-junction structure, leading to severe cholestatic liver disease. These findings contrast with those in the embryonic-lethal knockout mouse, highlighting differences in redundancy in junctional complexes between organs and species.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Cholestasis, Intrahepatic / genetics*
  • Cholestasis, Intrahepatic / physiopathology
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunoblotting
  • Immunohistochemistry
  • Mice
  • Mice, Knockout
  • Microscopy, Electron, Transmission
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / genetics*
  • Pedigree
  • Real-Time Polymerase Chain Reaction
  • Sequence Alignment
  • Species Specificity
  • Tight Junctions / genetics
  • Tight Junctions / pathology*
  • Zonula Occludens-2 Protein / genetics*


  • TJP2 protein, human
  • Zonula Occludens-2 Protein