SLC6A20

The Sodium/imino-acid transporter 1 (SIT1) protein is a member of the solute carrier superfamily of transport proteins. SIT1 is a Na⁺ and Cl⁻ coupled symporter,^[8] like other SLC6 amino acid and amine transporters, and a homolog of the Bacterial Leucine Transporter.^[9]

Among the SLC6 transporters, only SIT1 and SLC6A7 (PROT) prefer secondary amino acids.^[8] This selectivity arises due to the shape and highly conserved residues of the protein's binding site to exclude residues with extended site chains.^[10]

Natively, SIT1 forms a complex with ACE2 or collectrin, which assists in trafficking the transporter to the plasma membrane.^[11]

Mutation in the SLC6A20 gene are associated with iminoglycinuria.^[12][9]

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.^[13][14][15] 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.^[16]

SIT1 is proposed to modulate the activity of glycine and NMDA receptors,^[17] and variants in the SLC6A20 gene are associated with Hirschprung's disease.^[18][19][20]

SIT1 is also the primary proline transporter in the retinal pigment epithelium^[21] and supports the proline-dependent metabolism of these cells.^[22] Consequently, SLC6A20 gene variants are associated with retinal thickness^[23] and the retinal diseases Age-Related Macular Degeneration^[24] and Macular telangiectasia.^[25]