Solute carrier family 6 member 20 (SLC6A20)

Solute carrier family 6 member 20 (SLC6A20) is a sodium- and chloride-dependent amino acid transporter primarily responsible for the uptake of imino acids such as proline and secondary transport of glycine and betaine, with physiological roles in kidney, small intestine, and brain[1][3][7]. In the brain, SLC6A20 regulates extracellular levels of proline and glycine, influencing NMDA receptor (NMDAR) currents and synaptic plasticity, which are key in cognition and neuronal signaling[2][3]. Dysfunctions or mutations in SLC6A20 are associated with iminoglycinuria and hyperglycinuria, both aminoaciduria conditions, and it has been implicated in genetic susceptibility to severe COVID-19 respiratory failure[1][3]. The transporter may also represent a therapeutic target for disorders characterized by NMDAR hypofunction, such as schizophrenia, as SLC6A20 inhibition increases extracellular glycine and NMDAR activity[2][3]. SLC6A20 is also referred to by several aliases including SIT1 and XTRP3, and belongs to the sodium:neurotransmitter symporter family. Safety concerns primarily relate to the potential disruption of amino acid balance and consequent neurological or metabolic effects[3][5].

Other names

Sodium- and chloride-dependent transporter XTRP3SIT1XT3XTRP3Xtrp3IMINOSodium/imino-acid transporter 1Transporter rB21A homologneurotransmitter transporter RB21Aorphan transporter XT3sodium-dependent imino acid transporter 1sodium/imino-acid transporter 1proline IMINO transportersodium:neurotransmitter symporter SIT1

Inhibition of SLC6A20 increases extracellular glycine, enhancing NMDAR function[2][3] Substrate competition for glycine/proline transport