Solute carrier family 19 member 1 (SLC19A1) (SLC19A1)

Solute carrier family 19 member 1 (SLC19A1), commonly known as the reduced folate carrier (RFC), is a ubiquitously expressed membrane protein that serves as the primary transporter for reduced folates and antifolate drugs in mammalian cells [1, 6, 7]. It functions as a bidirectional anion exchanger, typically coupling the uptake of folate cofactors like 5-methyltetrahydrofolate with the efflux of intracellular organic phosphate anions such as thiamine pyrophosphate or adenine nucleotides [4, 11, 15]. This transport mechanism is vital for maintaining intracellular folate homeostasis, which supports essential processes like DNA synthesis, repair, and methylation [6, 8]. In oncology, SLC19A1 is a major determinant of sensitivity to antifolate chemotherapeutics, including methotrexate and pemetrexed, as its downregulation or mutation is a frequent cause of drug resistance [7, 11, 14]. Beyond its role in folate metabolism, SLC19A1 has recently been identified as a key transporter for cyclic dinucleotides (e.g., 2'3'-cGAMP), linking it to the STING-mediated innate immune response and potential cancer immunotherapies [11, 15]. Genetic variations in SLC19A1, such as the c.80A>G polymorphism, are associated with altered drug response and increased risk for various pathologies, including neural tube defects, cardiovascular disease, and certain immunodeficiencies [5, 8, 13, 16]. The protein's ubiquitous expression also means that its activity is a factor in the systemic toxicity of antifolate drugs, necessitating careful dosing in patients with specific genetic backgrounds [12, 14].

Other names

Reduced folate carrier 1RFC1Folate transporter 1Folate:anion antiporter SLC19A1Intestinal folate carrier 1Reduced folate transporter 1hRFCIFC-1RFT-1FOLTReduced folate carrier protein

Facilitative bidirectional anion exchange (antiporter) that couples the import of folates and antifolates to the export of organic phosphate anions (e.g., thiamine pyrophosphate, ATP, ADP) [4, 6, 11, 15].