Identification of TMEM230 mutations in familial Parkinson's disease

Nat Genet. 2016 Jul;48(7):733-9. doi: 10.1038/ng.3589. Epub 2016 Jun 6.


Parkinson's disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson's disease or parkinsonian disorders. The pathogenesis of Parkinson's disease remains largely elusive. Here we report a locus for autosomal dominant, clinically typical and Lewy body-confirmed Parkinson's disease on the short arm of chromosome 20 (20pter-p12) and identify TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. Disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson's disease, with implications for understanding the pathogenic mechanism of Parkinson's disease and for developing rational therapies.

Publication types

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

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Cells, Cultured
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Membrane Proteins / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Neurons / metabolism
  • Neurons / pathology*
  • Parkinson Disease / genetics*
  • Pedigree
  • Protein Transport / genetics
  • Sequence Homology, Amino Acid
  • Synaptic Vesicles / metabolism
  • Synaptic Vesicles / pathology*


  • Membrane Proteins
  • TMEM230 protein, human