Sodium-coupled neutral amino acid transporter 3

SLC38A3 encodes a sodium-coupled neutral amino acid transporter that mediates cotransport of specific amino acids (L-glutamine, L-histidine, L-asparagine) with sodium ions, coupled to proton antiport (UniProt: Q99624). The transporter plays a central role in the glutamate-GABA-glutamine cycle in brain, facilitating glutamine uptake from astrocytes for neurotransmitter replenishment in neurons.

SLC38A3 is expressed in neural tissue and is associated with developmental and epileptic encephalopathy 102 (DEE102), an autosomal recessive early-onset epilepsy characterized by refractory seizures and neurodevelopmental impairment (UniProt: Q99624). The protein also participates in amino acid homeostasis, nitrogen metabolism, and glucose regulation.

In Alzheimer's disease, SLC38A3 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log2 fold-change of +0.64 (Chaparral AD proteomics). This upregulation was observed in human brain via quantitative proteomics of multiple subcellular fractions, suggesting potential involvement in AD-related glutamatergic or metabolic dysfunction.