Mutations in NONO lead to syndromic intellectual disability and inhibitory synaptic defects

Nat Neurosci. 2015 Dec;18(12):1731-6. doi: 10.1038/nn.4169. Epub 2015 Nov 16.


The NONO protein has been characterized as an important transcriptional regulator in diverse cellular contexts. Here we show that loss of NONO function is a likely cause of human intellectual disability and that NONO-deficient mice have cognitive and affective deficits. Correspondingly, we find specific defects at inhibitory synapses, where NONO regulates synaptic transcription and gephyrin scaffold structure. Our data identify NONO as a possible neurodevelopmental disease gene and highlight the key role of the DBHS protein family in functional organization of GABAergic synapses.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Animals
  • Brain / pathology
  • Cells, Cultured
  • DNA-Binding Proteins
  • Humans
  • Intellectual Disability / diagnosis*
  • Intellectual Disability / genetics*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Mutation / genetics*
  • Neural Inhibition / genetics*
  • Nuclear Matrix-Associated Proteins / genetics*
  • Octamer Transcription Factors / genetics*
  • Pedigree
  • RNA-Binding Proteins / genetics*
  • Synapses / genetics*
  • Synapses / pathology


  • DNA-Binding Proteins
  • NONO protein, human
  • Nuclear Matrix-Associated Proteins
  • Octamer Transcription Factors
  • RNA-Binding Proteins