Relevance to Autism

Functional characterization of a de novo missense variant in the SLC6A3 gene originally identified in a simplex ASD case as part of a whole-exome sequencing study in 175 ASD parent-child trios (originally described by Neale et al. in a 2012 Nature report) showed that this variant (T356M) resulted in anomalous dopamine transporter function and hyperactivity when expressed in the DA neurons of Drosophila (Hamilton et al., 2013). A missense variant in this same gene (p.Ala559Val), previously identified in individuals with ADHD (Mazei-Robison et al., 2005) and bipolar disorder (Grunhage et al., 2000), was recently identified in two unrelated male ASD probands and shown to alter dopamine function and trafficking (Bowton et al., 2014).

Molecular Function

This gene encodes an amine transporter that terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals. Mutations in this gene are associated with Parkinsonism-dystonia infantile (PKDYS) [MIM:613135], while variation in the number of 40 bp tandem repeats in the 3'UTR of this gene is associated with idiopathic epilepsy, attention-deficit hyperactivity disorder, dependence on alcohol and cocaine, susceptibility to Parkinson disease and protection against nicotine dependence.

External Links

References

Model Summary

Rats overexpressing the dopamine transporter display behavioral and neurobiological abnormalities with relevance to repetitive disorders.

References