Relevance to Autism

Usmani et al., 2021 reported two biallelic and eight de novo heterozygous variants in the AP1G1 gene associated with a neurodevelopmental disorder characterized by mild to severe intellectual disability, epilepsy, and developmental delay in eleven families from different ethnicities; behavioral abnormalities were frequently observed in affected individuals, with three of the patients with de novo AP1G1 variants in this report presenting with autism spectrum disorder. Functional assessment of NDD-associated missense variants in this report demonstrated that while both recessively inherited and de novo missense variants affected AP1G1 protein levels, recessively inherited missense variants affected the endosome recycling pathway, whereas de novo missense variants resulted in abnormal cellular localization; furthermore, AP1G1 with NDD-associated missense variants failed to rescue morphological defects and lethality in ap1g1 -/- zebrafish. A de novo missense variant in AP1G1 had previously been identified in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014).

Molecular Function

Adaptins are important components of clathrin-coated vesicles transporting ligand-receptor complexes from the plasma membrane or from the trans-Golgi network to lysosomes. The adaptin family of proteins is composed of four classes of molecules named alpha, beta-, beta prime- and gamma- adaptins. Adaptins, together with medium and small subunits, form a heterotetrameric complex called an adaptor, whose role is to promote the formation of clathrin-coated pits and vesicles. The protein encoded by this gene is a gamma-adaptin protein and it belongs to the adaptor complexes large subunits family.

External Links

References