Relevance to Autism

Rahimi et al., 2022 clinically described a cohort of 12 unrelated individuals with variants in the ATP2B1 gene and an overlapping phenotype of mild to moderate developmental delay/intellectual disability; five of these individuals were diagnosed with autism spectrum disorder. Additional functional characterization of the nine ATP2B1 missense variants identified in affected individuals in this report by Ca2+ imaging in transfected HEK293 cells showed that all variants led to a signficant decrease in Ca2+ export capacity compared to wild-type, demonstrating their pathogencity.

Molecular Function

The protein encoded by this gene belongs to the family of P-type primary ion transport ATPases characterized by the formation of an aspartyl phosphate intermediate during the reaction cycle. These enzymes remove bivalent calcium ions from eukaryotic cells against very large concentration gradients and play a critical role in intracellular calcium homeostasis. The mammalian plasma membrane calcium ATPase isoforms are encoded by at least four separate genes and the diversity of these enzymes is further increased by alternative splicing of transcripts. The expression of different isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, suggesting that these pumps are functionally adapted to the physiological needs of particular cells and tissues. This gene encodes the plasma membrane calcium ATPase isoform 1.

External Links

References