SLC28A3: Solute Carrier Family 28 Member 3
Nucleoside Transporter CNT3 – Pharmacogenomics and Clinical Relevance
Gene Information Card
| Symbol | SLC28A3 |
|---|---|
| Full Name | Solute Carrier Family 28 Member 3 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.33 |
| NCBI Gene ID | 64078 ncbi.nlm.nih.gov/gene/64078 |
| Ensembl ID | ENSG00000156256 |
| UniProt ID | Q9HAS3 |
| OMIM ID | 608269 |
| HGNC ID | 11000 |
| Aliases | CNT3, concentrative nucleoside transporter 3 |
Description
SLC28A3 encodes the concentrative nucleoside transporter 3 (CNT3), a member of the solute carrier family 28. CNT3 mediates sodium-dependent uptake of physiological nucleosides and nucleoside analog drugs (e.g., gemcitabine, fludarabine, ribavirin). It is expressed in multiple tissues including intestine, kidney, liver, and pancreas, and plays a key role in drug absorption, distribution, and toxicity.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Gemcitabine toxicity | Reduced function variants (e.g., rs7853758) impair drug efflux, increasing intracellular accumulation and toxicity | ClinVar, PMID: 22992668 |
| Fludarabine sensitivity | Altered transport efficiency due to SLC28A3 polymorphisms affects drug efficacy and adverse events | ClinVar, PMID: 20022977 |
| Ribavirin-induced anemia | SLC28A3 variants influence ribavirin uptake into erythrocytes, modulating anemia risk | ClinVar, PMID: 20628086 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Small intestine | 12.5 | High |
| Kidney | 9.8 | Medium |
| Liver | 7.3 | Medium |
| Pancreas | 6.1 | Medium |
| Lung | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Caco-2 | 15.2 | Intestinal epithelial model |
| HepG2 | 8.7 | Hepatocellular carcinoma |
| HEK293 | 4.5 | Embryonic kidney |
| A549 | 1.8 | Lung carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs7853758 (c.1236G>A) | SNV | 0.08 (European) | Reduced transport activity; associated with gemcitabine toxicity |
| rs56350726 (c.1465C>T) | SNV | 0.02 (global) | Missense; decreased nucleoside uptake |
| rs2305649 (c.169C>T) | SNV | 0.15 (European) | Synonymous; may affect splicing |
Mutation functional classification
Loss of Function (LOF)
rs7853758 (c.1236G>A) reduces CNT3 transport capacity for gemcitabine and other nucleoside analogs.
Gain of Function (GOF)
No well-characterized gain-of-function variants reported in SLC28A3.
Dominant Negative (DN)
Not described for SLC28A3.
View complete mutation data：
Gene Ontology (GO)
| • nucleoside transmembrane transporter activity (GO:0005337) | • sodium-dependent nucleoside transport (GO:0015860) |
| • plasma membrane (GO:0005886) | • response to drug (GO:0042493) |
Pathways
• Nucleoside transport (REACT_17015)
• Gemcitabine pathway (PharmGKB PA166152994)
• Fludarabine pathway (PharmGKB PA166152995)
Protein Summary
CNT3 is a 691-amino acid transmembrane protein with 13 predicted helices. It functions as a sodium-nucleoside symporter, transporting both purine and pyrimidine nucleosides. The protein is glycosylated and localized to the apical membrane of epithelial cells. Its structure includes a conserved nucleoside binding domain critical for substrate recognition.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SLC28A3 Knockout HEK293 Cell Line | EDJ-KQ15322 | Human | 64078 | Details Get a Quote |
| SLC28A3 Knockout HeLa Cell Line | EDJ-KQ57017 | Human | 64078 | Details Get a Quote |
| SLC28A3 Knockout A-549 Cell Line | EDJ-KQ65523 | Human | 64078 | Details Get a Quote |
| SLC28A3 Knockout HCT 116 Cell Line | EDJ-KQ73958 | Human | 64078 | Details Get a Quote |
