Solute carrier family 28 member 3 (SLC28A3), also known as Concentrative nucleoside transporter 3 (CNT3), is a transmembrane protein from the CNT family that functions as a sodium-coupled symporter for purine and pyrimidine nucleosides, as well as a wide variety of nucleoside-derived drugs, including anticancer and antiviral agents. SLC28A3 is notable for its broad substrate specificity and tissue distribution, being highly expressed in pancreas, bone marrow, and mammary gland, with lower levels in intestine, lung, prostate, testis, and liver. Functionally, it plays a key role in nucleoside salvage, intracellular metabolism, and drug pharmacokinetics. Variants of SLC28A3 can impact drug toxicity risk, such as anthracycline-induced cardiotoxicity in cancer therapy, and act as pharmacogenomic biomarkers for patient selection and monitoring. As a drug transporter, it is a validated therapeutic target with safety implications tied to its function and genetic variation.
Other names
SLC28A3CNT3Concentrative Na(+)-nucleoside cotransporter 3hCNT3Concentrative nucleoside transporter 3Sodium-coupled nucleoside transporter 3N3/cib subtypeSolute carrier family 28 (concentrative nucleoside transporter), member 3
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Mechanism of action
Symporter: couples one nucleoside with two sodium ions or one proton. Facilitates cellular uptake of nucleoside drugs for cytotoxic or antiviral effects. Mutation or inhibition reduces cellular uptake and toxicity of some anticancer drugs (e.g., doxorubicin).
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Biological functions
Nucleoside transport (purines and pyrimidines)Homeostasis of endogenous nucleosidesCellular salvage of nucleosidesTransport of nucleoside-derived drugs (anticancer/antiviral)Regulation of neurotransmission, vascular tone, and adenosine concentration near receptorsRenal reabsorption and intracellular metabolism of nucleosides
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Disease associations
Cancer (specific roles in leukemia, acute lymphoblastic leukemia, and prostate cancer)Drug toxicity/modulation (e.g., anthracycline-induced cardiotoxicity, gemcitabine toxicity)Hematologic cancerMetastatic breast cancer outcome predictionOther: progression to castration-resistant prostate cancer (CRPC)
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Safety considerations
Drug toxicity: Overexpression may increase cytotoxicity of nucleoside-derived drugs (e.g., anticancer agents, gemcitabine or doxorubicin)Pharmacogenomic variation: Specific SNPs confer altered sensitivity to agents, including risk for drug-induced cardiotoxicity (doxorubicin)Potential for resistance: SLC28A3-mediated drug transport influences therapeutic response and resistance
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Interacting drugs
Gemcitabine
7 more in the full profile.
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Biomarkers
SNP rs7853758, rs885004, rs56350726, rs11140490 (associated with cancer risk and drug-induced cardiotoxicity)Expression level of SLC28A3 (predicts drug response/toxicity)Splice variant status (potential biomarker in specific tissues)
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