Relevance to Autism

Rare de novo variants in the BAIAP2L1 gene have been identified in ASD probands, including a de novo missense variant (p.Ala481Val) in a proband from the Simons Simplex Collection (Iossifov et al., 2014; Sanders et al., 2015; Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020). Functional assessment of the ASD-associated p.Ala481Val missense variant in Drosophila using an overexpression-based strategy in Macrogliese et al., 2022 demonstrated that flies overexpressing BAIAP2L1-p.Ala481Val exhibited a smaller, more crumpled wing phenotype compared to the reference allele, consistent with a gain-of-function effect.

Molecular Function

This gene encodes a member of the IMD (IRSp53/MIM homology domain) family. Members of this family can be subdivided in two groups, the IRSp53-like and MIM-like, based on the presence or absence of the SH3 (Src homology 3) domain. The protein encoded by this gene contains a conserved IMD, also known as F-actin bundling domain, at the N-terminus, and a canonical SH3 domain near the C-terminus, so it belongs to the IRSp53-like group. This protein is the substrate for insulin receptor tyrosine kinase and binds to the small GTPase Rac. It is involved in signal transduction pathways that link deformation of the plasma membrane and remodeling of the actin cytoskeleton. It also promotes actin assembly and membrane protrusions when overexpressed in mammalian cells, and is essential to the formation of a potent actin assembly complex during EHEC (Enterohemorrhagic Escherichia coli) pedestal formation.

External Links

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