Relevance to Autism

Hellman et al., 2024 reported a p.Arg295Leu missense variant in the CAPZA2 gene in a proband diagnosed with autism and presenting with developmental delay and intellectual disability; this missense variant had been previously reported in a proband presenting with developmental delay and a history of seizures in Huang et al., 2020. Guo et al., 2025 subsequently found that CAPZA2 heterozygous knockout mice demonstrated reduced expression in the hippocampus and prefrontal cortex, as well as exhibited motor dysfunction and anxiety-like behaviors, impairments in spatial and non-spatial memory, and deficits in social interactions; these phenotypes were mirrored in mice heterozygous for the human-specific Arg259Leu missense variant previously reported in Huang et al., 2020 and Hellman et al., 2024. Huang et al., 2020 also reported a proband with a p.Lys256Glu missense variant who was diagnosed with autism and presented with developmental delay and intellectual disability; functional studies of this variant in Drosophila demonstrated a reduced ability to rescue the lethality phenotype in flies that were null for cpa (the CAPZA orthologue in Drosophila), consistent with a partial loss-of-function effect.

Molecular Function

The protein encoded by this gene is a member of the F-actin capping protein alpha subunit family. It is the alpha subunit of the barbed-end actin binding protein Cap Z. By capping the barbed end of actin filaments, Cap Z regulates the growth of the actin filaments at the barbed end.

External Links

References