Heterozygous variants in ACTL6A, encoding a component of the BAF complex, are associated with intellectual disability

Hum Mutat. 2017 Oct;38(10):1365-1371. doi: 10.1002/humu.23282. Epub 2017 Jul 10.


Pathogenic variants in genes encoding components of the BRG1-associated factor (BAF) chromatin remodeling complex have been associated with intellectual disability syndromes. We identified heterozygous, novel variants in ACTL6A, a gene encoding a component of the BAF complex, in three subjects with varying degrees of intellectual disability. Two subjects have missense variants affecting highly conserved amino acid residues within the actin-like domain. Missense mutations in the homologous region in yeast actin were previously reported to be dominant lethal and were associated with impaired binding of the human ACTL6A to β-actin and BRG1. A third subject has a splicing variant that creates an in-frame deletion. Our findings suggest that the variants identified in our subjects may have a deleterious effect on the function of the protein by disturbing the integrity of the BAF complex. Thus, ACTL6A gene mutation analysis should be considered in patients with intellectual disability, learning disabilities, or developmental language disorder.

Keywords: ACTL6A; BAF complex; intellectual disability; speech delay.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / genetics*
  • Adolescent
  • Child
  • Chromatin Assembly and Disassembly / genetics
  • Chromosomal Proteins, Non-Histone / genetics*
  • DNA Helicases / genetics
  • DNA-Binding Proteins / genetics*
  • Exome
  • Face
  • Female
  • Hand Deformities, Congenital / genetics*
  • Hand Deformities, Congenital / physiopathology
  • Heterozygote
  • Humans
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Male
  • Micrognathism / genetics
  • Micrognathism / physiopathology
  • Multiprotein Complexes / genetics
  • Mutation, Missense / genetics*
  • Nuclear Proteins / genetics
  • Protein Binding
  • Transcription Factors / genetics


  • ACTL6A protein, human
  • Actins
  • BANF1 protein, human
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Multiprotein Complexes
  • Nuclear Proteins
  • Transcription Factors
  • SMARCA4 protein, human
  • DNA Helicases