The expanding biology of the C9orf72 nucleotide repeat expansion in neurodegenerative disease

Nat Rev Neurosci. 2016 Jun;17(6):383-95. doi: 10.1038/nrn.2016.38. Epub 2016 May 6.


A nucleotide repeat expansion (NRE) within the chromosome 9 open reading frame 72 (C9orf72) gene was the first of this type of mutation to be linked to multiple neurological conditions, including amyotrophic lateral sclerosis and frontotemporal dementia. The pathogenic mechanisms through which the C9orf72 NRE contributes to these disorders include loss of C9orf72 function and gain-of-function mechanisms of C9orf72 driven by toxic RNA and protein species encoded by the NRE. These mechanisms have been linked to several cellular defects - including nucleocytoplasmic trafficking deficits and nuclear stress - that have been observed in both patients and animal models.

Publication types

  • Review

MeSH terms

  • Animals
  • Base Sequence / physiology*
  • C9orf72 Protein
  • Humans
  • Neurodegenerative Diseases / genetics*
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Proteins / genetics*
  • Proteins / metabolism*
  • Trinucleotide Repeat Expansion / physiology*


  • C9orf72 Protein
  • C9orf72 protein, human
  • Proteins