Identification of TMEM230 mutations in familial Parkinson's disease

Han Xiang Deng*, Yong Shi, Yi Yang, Kreshnik B. Ahmeti, Nimrod Miller, Cao Huang, Lijun Cheng, Hong Zhai, Sheng Deng, Karen Nuytemans, Nicola J. Corbett, Myung Jong Kim, Hao Deng, Beisha Tang, Ziquang Yang, Yanming Xu, Piu Chan, Bo Huang, Xiao Ping Gao, Zhi SongZhenhua Liu, Faisal Fecto, Nailah Siddique, Tatiana Foroud, Joseph Jankovic, Bernardino Ghetti, Daniel A. Nicholson, Dimitri Krainc, Onur Melen, Jeffery M. Vance, Margaret A. Pericak-Vance, Yong Chao Ma, Ali H. Rajput, Teepu Siddique

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)733-739
Number of pages7
JournalNature Genetics
Issue number7
StatePublished - Jul 1 2016

ASJC Scopus subject areas

  • Genetics


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