Hereditary folate malabsorption due to a mutation in the external gate of the proton-coupled folate transporter SLC46A1.

ABSTRACT: Hereditary folate malabsorption (HFM) is an autosomal recessive disorder characterized by impaired intestinal folate absorption and impaired folate transport across the choroid plexus due to loss of function of the proton-coupled folate transporter (PCFT-SLC46A1). We report a novel mutation, causing HFM, affecting a residue located in the 11th transmembrane helix within the external gate. The mutant N411K-PCFT was stable, trafficked to the cell membrane, and had sufficient residual activity to characterize the transport defect and the structural requirements at this site for gate function. The influx V_max of the N411K mutant was markedly decreased, as was the affinity for most, but not all, folate/antifolate substrates. The greatest loss of activity was for 5-methyltetrahydrofol

SUBMITTER: Aluri S 

PROVIDER: S-EPMC5761628 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature