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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC28A1
solute carrier family 28 member 1
Chromosome 15 · 15q25.3
NCBI Gene: 9154Ensembl: ENSG00000156222.12HGNC: HGNC:11001UniProt: B7Z3L5
53PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
apical plasma membraneuridine transmembrane transportazole transmembrane transportpyrimidine-containing compound transmembrane transporturidine-cytidineuriaplacenta praeviaAbnormality of the skeletal systemretinal degeneration
✦AI Summary

SLC28A1 encodes CNT1 (concentrative nucleoside transporter-1), a sodium-dependent symporter that mediates pyrimidine nucleoside uptake 1. CNT1 specifically transports uridine, cytidine, and thymidine across the plasma membrane by coupling their transport to the transmembrane sodium gradient, also transporting adenosine with high affinity but lower velocity 2. The protein localizes primarily to epithelial tissues, including renal brush border membranes where it participates in nucleoside reabsorption 3. CNT1 plays critical roles in nucleoside salvage pathways and adenosine signaling termination 1. As a key determinant of nucleoside analog disposition, CNT1 significantly influences the pharmacokinetics and efficacy of anticancer and antiviral nucleoside drugs 2. CNT1 expression is transcriptionally regulated by hepatocyte nuclear factor-4alpha and suppressed by bile acids 4. Loss-of-function mutations in SLC28A1 cause uridine-cytidineuria, a rare pyrimidineuria with unclear clinical consequences 5. Notably, SLC28A1 knockout provides cardioprotection against doxorubicin-induced cardiotoxicity in human cardiomyocytes 6, suggesting CNT1-mediated drug uptake contributes to anthracycline toxicity. Additionally, SLC28A1 variants influence metformin response in diabetes treatment 7.

Sources cited
1
SLC28A1 encodes CNT1, a pyrimidine-nucleoside preferring sodium-dependent concentrative transporter; substrate specificity and nucleoside salvage pathway involvement
PMID: 12856181
2
CNT1 structure-function, substrate selectivity, and pharmacological role in nucleoside-based therapeutics
PMID: 18668436
3
Renal nucleoside transporter function and localization in renal epithelial cells; physiological and clinical implications
PMID: 17215872
4
Transcriptional regulation of CNT1 by hepatocyte nuclear factor-4alpha and suppression by bile acids
PMID: 19228884
5
SLC28A1 mutations cause uridine-cytidineuria (URCTU); inborn error of nucleoside transporter
PMID: 35955904
6
SLC28A1 knockout provides protective effect against doxorubicin-induced cardiotoxicity in hiPSC-derived cardiomyocytes
PMID: 38510289
7
SLC28A1 variants influence metformin response variability in diabetes treatment
PMID: 40532247
Disease Associationsⓘ21
uridine-cytidineuriaOpen Targets
0.58Moderate
placenta praeviaOpen Targets
0.28Weak
Abnormality of the skeletal systemOpen Targets
0.27Weak
retinal degenerationOpen Targets
0.26Weak
myopiaOpen Targets
0.11Weak
pathological myopiaOpen Targets
0.11Weak
cancerOpen Targets
0.08Suggestive
neoplasmOpen Targets
0.07Suggestive
Crohn's diseaseOpen Targets
0.06Suggestive
Adult-onset autosomal recessive sideroblastic anemiaOpen Targets
0.05Suggestive
Hemolytic anemia due to red cell pyruvate kinase deficiencyOpen Targets
0.05Suggestive
dehydrated hereditary stomatocytosisOpen Targets
0.05Suggestive
nephrotic syndromeOpen Targets
0.05Suggestive
formiminoglutamic aciduriaOpen Targets
0.05Suggestive
colorectal carcinomaOpen Targets
0.04Suggestive
Familial LCAT deficiencyOpen Targets
0.04Suggestive
LCAT deficiencyOpen Targets
0.04Suggestive
atypical hemolytic-uremic syndrome with I factor anomalyOpen Targets
0.04Suggestive
atypical hemolytic-uremic syndrome with MCP/CD46 anomalyOpen Targets
0.04Suggestive
atypical hemolytic-uremic syndrome with thrombomodulin anomalyOpen Targets
0.04Suggestive
Uridine-cytidineuriaUniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
SLC22A1Protein interaction87%CDAProtein interaction70%SLC29A2Protein interaction60%SLC29A3Protein interaction57%SLC29A1Protein interaction55%SLC28A3Shared pathway50%
Tissue Expression6 tissues
Liver
100%
Heart
1%
Brain
0%
Ovary
0%
Lung
0%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
SLC28A1SLC22A1CDASLC29A2SLC29A3SLC29A1SLC28A3
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O00337
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.05LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.85 [0.69–1.05]
RankingsWhere SLC28A1 stands among ~20K protein-coding genes
  • #8,496of 20,598
    Most Researched53
  • #10,447of 17,882
    Most Constrained (LOEUF)1.05
Genes detectedSLC28A1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Functional Validation of Doxorubicin-Induced Cardiotoxicity-Related Genes.
PMID: 38510289
JACC CardioOncol · 2024
1.00
2
Gene-gene Interaction Analyses for Atrial Fibrillation.
PMID: 27824142
Sci Rep · 2016
0.90
3
Inborn Errors of Nucleoside Transporter (NT)-Encoding Genes (
PMID: 35955904
Int J Mol Sci · 2022
0.80
4
The concentrative nucleoside transporter family, SLC28.
PMID: 12856181
Pflugers Arch · 2004
0.70
5
Hepatocyte nuclear factor-4alpha and bile acids regulate human concentrative nucleoside transporter-1 gene expression.
PMID: 19228884
Am J Physiol Gastrointest Liver Physiol · 2009
0.60