Shining a light on CNTNAP2: complex functions to complex disorders

Eur J Hum Genet. 2014 Feb;22(2):171-8. doi: 10.1038/ejhg.2013.100. Epub 2013 May 29.


The genetic basis of complex neurological disorders involving language are poorly understood, partly due to the multiple additive genetic risk factors that are thought to be responsible. Furthermore, these conditions are often syndromic in that they have a range of endophenotypes that may be associated with the disorder and that may be present in different combinations in patients. However, the emergence of individual genes implicated across multiple disorders has suggested that they might share similar underlying genetic mechanisms. The CNTNAP2 gene is an excellent example of this, as it has recently been implicated in a broad range of phenotypes including autism spectrum disorder (ASD), schizophrenia, intellectual disability, dyslexia and language impairment. This review considers the evidence implicating CNTNAP2 in these conditions, the genetic risk factors and mutations that have been identified in patient and population studies and how these relate to patient phenotypes. The role of CNTNAP2 is examined in the context of larger neurogenetic networks during development and disorder, given what is known regarding the regulation and function of this gene. Understanding the role of CNTNAP2 in diverse neurological disorders will further our understanding of how combinations of individual genetic risk factors can contribute to complex conditions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Genetic Predisposition to Disease
  • Humans
  • Language Development Disorders / genetics
  • Membrane Proteins / genetics*
  • Molecular Sequence Data
  • Mutation, Missense
  • Nerve Net / pathology
  • Nerve Tissue Proteins / genetics*
  • Nervous System Diseases / genetics
  • Polymorphism, Single Nucleotide
  • Risk Factors


  • CNTNAP2 protein, human
  • Membrane Proteins
  • Nerve Tissue Proteins