Relevance to Autism

A de novo missense variant in the ACTB gene has been identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014). Gain-of-function variants in the ACTB gene are associated with Baraitser-Winter syndrome 1 (BRWS; OMIM 243310), and while intellectual disability is frequently observed in individals with this syndrome (29/33 in Verloes et al., 2015), to date the prevalence of ASD or autistic features has not been examined. Cuvertino et al., 2017 reported 33 individuals with loss-of-function variants in the ACTB gene who presented with developmental delay, apparent intellectual disability, increased frequency of internal organ malformations, growth retardation, and a recognizable facial gestalt hat was distinct from characteristics of individuals with BRWS; five individuals from this cohort presented with autism spectrum disorder. Lesieur-Sebellin et al., 2025 described a cohort of 19 individuals with either a heterozygous deletion including ACTB or a heterozygous truncating variant in the ACTB gene presenting with speech delay (15/17), intellectual disability/learning disability (15/17), behavioral abnormalities (12/17), motor delay (9/17), growth restriction (9/18), and recognizable dysmorphic features (13/18); autism spectrum disorder was reported in 4 individuals.

Molecular Function

This gene encodes one of six different actin proteins. Actins are highly conserved proteins that are involved in cell motility, structure, integrity, and intercellular signaling. The encoded protein is a major constituent of the contractile apparatus and one of the two nonmuscle cytoskeletal actins that are ubiquitously expressed. Mutations in this gene cause Baraitser-Winter syndrome 1, which is characterized by intellectual disability with a distinctive facial appearance in human patients.

External Links

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