Solute carrier family 6, member 20 also known as SLC6A20 is a gene that encodes for the Sodium/imino-acid transporter 1 (SIT1) protein, a plasma membrane proline and glycine transporter.
The Sodium/imino-acid transporter 1 (SIT1) protein is a member of the solute carrier superfamily of transport proteins. SIT1 is a Na<sup>+</sup> and Cl<sup>âÂÂ</sup> coupled symporter, like other SLC6 amino acid and amine transporters, and a homolog of the Bacterial Leucine Transporter.
Among the SLC6 transporters, only SIT1 and SLC6A7 (PROT) prefer secondary amino acids. This selectivity arises due to the shape and highly conserved residues of the protein's binding site to exclude residues with extended site chains.
Natively, SIT1 forms a complex with ACE2 or collectrin, which assists in trafficking the transporter to the plasma membrane.
Mutation in the SLC6A20 gene are associated with iminoglycinuria.
One of a cluster of 6 genes (SLC6A20, LZTFL1, CCR9, FYCO1, CXCR6 and XCR1) on chromosome 3 at location 3p21.31 associated with a genetic susceptibility to COVID-19 respiratory failure. Of these, SIT1 expression can control ACE2 trafficking to the plasma membrane and thereby SLC6A20 gene variants are proposed to alter the availability of viral receptors on the cell surface.
SIT1 is proposed to modulate the activity of glycine and NMDA receptors, and variants in the SLC6A20 gene are associated with Hirschprung's disease.
SIT1 is also the primary proline transporter in the retinal pigment epithelium and supports the proline-dependent metabolism of these cells. Consequently, SLC6A20 gene variants are associated with retinal thickness and the retinal diseases Age-Related Macular Degeneration and Macular telangiectasia.