Relevance to Autism

De novo variants in the ITGA8 gene have been identified in ASD probands, including two de novo missense variants in probands from the Simons Simplex Collection and the Autism Sequencing Consortium (Iossifov et al., 2014; Yuen et al., 2017; Turner et al., 2017; Satterstrom et al., 2020). Functional assessment of the ASD-associated p.Arg748Cys missense variant, which was originally identified in a proband from the Simons Simplex Collection, in Drosophila using an overexpression-based strategy in Macrogliese et al., 2022 demonstrated that flies overexpressing ITGA8-p.Arg748Gly failed to reduce the expected viability to the extent of the corresponding reference allele upon overexpression, indicating a loss-of-function effect.

Molecular Function

Integrins are heterodimeric transmembrane receptor proteins that mediate numerous cellular processes including cell adhesion, cytoskeletal rearrangement, and activation of cell signaling pathways. Integrins are composed of alpha and beta subunits. This gene encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1 protein. The encoded protein is a single-pass type 1 membrane protein that contains multiple FG-GAP repeats. This repeat is predicted to fold into a beta propeller structure. This gene regulates the recruitment of mesenchymal cells into epithelial structures, mediates cell-cell interactions, and regulates neurite outgrowth of sensory and motor neurons. The integrin alpha8beta1 protein thus plays an important role in wound-healing and organogenesis. Mutations in this gene have been associated with renal hypodysplasia/aplasia-1 (RHDA1) and with several animal models of chronic kidney disease.

External Links

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