ATPV1B2 encodes a component of the vacuolar ATPase (V-ATPase, also known as H+-ATPase), a multi subunit enzyme that mediates acidification of eukaryotic intracellular organelles. The mutation c.1516 C>T (p. Arg506X) in ATP6V1B2 inserts a premature stop codon and results in a truncated protein. Conservation analysis of amino acids in nine ATP6V1B2 orthologous indicates that the last five amino acids, from residues 506 to 511, are highly conserved. Three-dimensional protein structure modelling suggested the p.Arg506X resulted in failure of hydrogen bond formation between Tyr 504 and Asp 507 in ATP6V1B2. In vitro pathogenic evaluation showed that the ATP6V1B2 p.Arg506X mutation exerted a haploinsufficient effect on wild-type ATP6V1B2 and resulted in abnormal acidification in lysosomes. Sanger sequencing for ATP6V1B2 gene or targeted capture NGS including ATP6V1B2 gene could be used for diagnostic testing.
ATP6V1B2