Functional analysis of mutations in the glucose-6-phosphate transporter that cause glycogen storage disease type Ib

Abstract

The glucose-6-phosphate transporter (G6PT) deficient in glycogen storage disease type Ib is a phosphate (P i )-linked antiporter capable of G6P: P i and P i :P i exchanges. We previously characterized G6PT mutations by measuring G6P uptake activities in microsomes co-expressing G6PT and glucose-6-phosphatase-α. Here we report a new assay, based on reconstituted proteoliposomes carrying only G6PT, and characterize G6P and P i uptake activities of 23 G6PT mutations. We show that co-expression and G6PT-only assays are equivalent in measuring G6PT activity. However, the p.Q133P mutation exhibits differential G6P and P i transport activities, suggesting that characterizing G6P and P i transport activities of G6PT mutations may yield insights to this genetic disorder.