Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample

J Mol Neurosci. 2020 Feb;70(2):219-229. doi: 10.1007/s12031-019-01456-z. Epub 2019 Dec 14.


Autism spectrum disorder (ASD) is a neurodevelopmental disorder with high phenotypic and genetic heterogeneity. Whole-exome sequencing studies have shown that de novo single-nucleotide variations (SNVs) play an important role in sporadic ASD. The present study aimed to search for de novo SNVs using whole-exome sequencing in 59 unrelated Chinese ASD sporadic trios, and found 24 genes (including five reported ASD candidate genes CACNA1D, ACHE, YY1, TTN, and FBXO11) with de novo harmful SNVs. Five genes (CACNA1D, JAK2, ACHE, MAPK7, and PRKAG2) classified as "medium-confidence" genes were found to be related to ASD using the Phenolyzer gene analysis tool, which predicts the correlation between the candidate genes and the ASD phenotype. De novo SNVs in JAK2, MAPK7, and PRKAG2 were first found in ASD. Both JAK2 and MAPK7 were involved in the regulation of the MAPK signaling pathway. Gene co-expression and inter-gene interaction networks were constructed and gene expression data in different brain regions were further extracted, revealing that JAK2 and MAPK7 genes were associated with certain previously reported ASD genes and played an important role in early brain development. The findings of this study suggest that the aforementioned five reported ASD genes and JAK2 and MAPK7 may be related to ASD susceptibility. Further investigations of expression studies in cellular and animal models are needed to explore the mechanism underlying the involvement of JAK2 and MAPK7 in ASD.

Keywords: Autism spectrum disorder; De novo single-nucleotide variations; JAK2; MAPK7; Whole-exome sequencing.

MeSH terms

  • AMP-Activated Protein Kinases / genetics
  • Acetylcholinesterase / genetics
  • Adolescent
  • Autism Spectrum Disorder / genetics*
  • Calcium Channels, L-Type / genetics
  • Child
  • China
  • Female
  • GPI-Linked Proteins / genetics
  • Humans
  • Janus Kinase 2 / genetics*
  • Male
  • Mitogen-Activated Protein Kinase 7 / genetics*
  • Pedigree
  • Polymorphism, Single Nucleotide*
  • Whole Genome Sequencing


  • CACNA1D protein, human
  • Calcium Channels, L-Type
  • GPI-Linked Proteins
  • JAK2 protein, human
  • Janus Kinase 2
  • PRKAG2 protein, human
  • MAPK7 protein, human
  • Mitogen-Activated Protein Kinase 7
  • AMP-Activated Protein Kinases
  • ACHE protein, human
  • Acetylcholinesterase