Molecular modelling of the Norrie disease protein predicts a cystine knot growth factor tertiary structure

Nat Genet. 1993 Dec;5(4):376-80. doi: 10.1038/ng1293-376.


The X-lined gene for Norrie disease, which is characterized by blindness, deafness and mental retardation has been cloned recently. This gene has been thought to code for a putative extracellular factor; its predicted amino acid sequence is homologous to the C-terminal domain of diverse extracellular proteins. Sequence pattern searches and three-dimensional modelling now suggest that the Norrie disease protein (NDP) has a tertiary structure similar to that of transforming growth factor beta (TGF beta). Our model identifies NDP as a member of an emerging family of growth factors containing a cystine knot motif, with direct implications for the physiological role of NDP. The model also sheds light on sequence related domains such as the C-terminal domain of mucins and of von Willebrand factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Blindness / genetics*
  • Deafness / genetics*
  • Humans
  • Intellectual Disability / genetics*
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Tertiary
  • Sex Chromosome Aberrations / genetics*
  • X Chromosome*
  • von Willebrand Factor


  • von Willebrand Factor