ATP6V0A1 encoding the a1-subunit of the V0 domain of vacuolar H⁺-ATPases is essential for brain development in humans and mice.

ABSTRACT: Vacuolar H⁺-ATPases (V-ATPases) transport protons across cellular membranes to acidify various organelles. ATP6V0A1 encodes the a1-subunit of the V0 domain of V-ATPases, which is strongly expressed in neurons. However, its role in brain development is unknown. Here we report four individuals with developmental and epileptic encephalopathy with ATP6V0A1 variants: two individuals with a de novo missense variant (R741Q) and the other two individuals with biallelic variants comprising one almost complete loss-of-function variant and one missense variant (A512P and N534D). Lysosomal acidification is significantly impaired in cell lines expressing three missense ATP6V0A1 mutants. Homozygous mutant mice harboring human R741Q (Atp6v0a1^R741Q) and A512P (Atp6v0a1^A512P

SUBMITTER: Aoto K 

PROVIDER: S-EPMC8032687 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature