In our LeuT-based homology model (Fig. 5), the aliphatic side-chain of Ala314 is pointing outward with respect to the S2 pocket, and thus its increased bulk when replaced by valine can be expected to have less impact on DAT function than the other DAT-mutants identified in the classical DTDS with infantile parkinsonism dystonia phenotype. This evidence concerns the gene SLC6A3 and SLC6A3-related dopamine transporter deficiency syndrome.