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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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SLC22A2
solute carrier family 22 member 2
Chromosome 6 · 6q25.3
NCBI Gene: 6582Ensembl: ENSG00000112499.13HGNC: HGNC:10966UniProt: O15244
143PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
organic cation transportamine transmembrane transporter activityacetylcholine transmembrane transporter activityneurotransmitter transmembrane transporter activitychronic kidney diseasecoronary artery diseasekidney failureprostate carcinoma
✦AI Summary

SLC22A2 (OCT2) is an organic cation transporter abundantly expressed in kidney tissue that facilitates bidirectional transport of endogenous and exogenous cationic compounds 1. As a member of the SLC22 transporter family, SLC22A2 plays a pivotal role in drug disposition and regulates key metabolic pathways and signaling molecules 2. The transporter mediates cellular uptake of pharmacologically important drugs including metformin, cisplatin, cimetidine, and lamivudine, with isoform-specific substrate selectivity differences 1. SLC22A2 genetic polymorphisms significantly influence individual drug response and toxicity. Variants rs316019 and rs316009 associate with increased metformin adverse drug reactions (7.3-fold higher odds for homozygous carriers) 3, while rs316019 also associates with oxaliplatin-induced hematological toxicity severity 4. Promoter haplotypes show ethnicity-specific variation; African-specific haplotypes decrease gene expression and potentially alter pharmacokinetic profiles 1. Functionally, SLC22A2 inhibition by compounds like carvedilol and cimetidine reduces cisplatin accumulation in renal tissues, alleviating nephrotoxicity without compromising anti-tumor efficacy 5. Additionally, dolutegravir's inhibition of SLC22A2-mediated creatinine secretion causes a predictable 10-14% serum creatinine increase without affecting true glomerular filtration 6. These findings highlight SLC22A2's importance as a pharmacogenomic biomarker for precision medicine applications.

Sources cited
1
SLC22A2 is abundantly expressed in kidney, transports metformin and other cationic drugs, and shows ethnicity-specific promoter polymorphisms affecting gene expression
PMID: 35143948
2
SLC22 transporters including SLC22A2 regulate metabolic pathways and signaling molecules and have roles in homeostasis
PMID: 29309257
3
SLC22A2 variants rs316019 and rs316009 associate with metformin adverse drug reactions with 7.3-fold increased odds for homozygous carriers
PMID: 39928707
4
SLC22A2 rs316019 variant associates with oxaliplatin-induced hematological toxicity severity in colorectal cancer patients
PMID: 36331012
5
SLC22A2 inhibition by carvedilol and cimetidine reduces cisplatin renal uptake and alleviates nephrotoxicity without affecting anti-tumor effects
PMID: 40044066
6
Dolutegravir inhibits SLC22A2-mediated creatinine secretion, causing predictable 10-14% serum creatinine increase without affecting true renal function
PMID: 25858606
Disease Associationsⓘ20
chronic kidney diseaseOpen Targets
0.54Moderate
coronary artery diseaseOpen Targets
0.44Moderate
kidney failureOpen Targets
0.44Moderate
prostate carcinomaOpen Targets
0.43Moderate
cardiovascular diseaseOpen Targets
0.39Weak
type 2 diabetes mellitusOpen Targets
0.36Weak
nervous system diseaseOpen Targets
0.33Weak
Precordial painOpen Targets
0.32Weak
psychiatric disorderOpen Targets
0.31Weak
vascular diseaseOpen Targets
0.26Weak
renal osteodystrophyOpen Targets
0.25Weak
angina pectorisOpen Targets
0.23Weak
nephrolithiasisOpen Targets
0.21Weak
atherosclerosisOpen Targets
0.13Weak
bladder calculusOpen Targets
0.11Weak
alcohol drinkingOpen Targets
0.11Weak
prostate cancerOpen Targets
0.10Suggestive
Myocardial IschemiaOpen Targets
0.08Suggestive
cystOpen Targets
0.08Suggestive
coronary artery bypassOpen Targets
0.08Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IGF2RProtein interaction89%SLC47A2Protein interaction89%EHMT2Protein interaction74%SLC31A1Protein interaction71%SLC47A1Protein interaction69%SLC22A1Shared pathway61%
Tissue Expression6 tissues
Brain
100%
Liver
38%
Ovary
6%
Lung
0%
Heart
0%
Bone Marrow
0%
Gene Interaction Network
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SLC22A2IGF2RSLC47A2EHMT2SLC31A1SLC47A1SLC22A1
PROTEIN STRUCTURE
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PDB8ET9 · 3.61 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.12LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.81 [0.59–1.12]
RankingsWhere SLC22A2 stands among ~20K protein-coding genes
  • #3,206of 20,598
    Most Researched143 · top quartile
  • #11,484of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedSLC22A2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The SLC22 Transporter Family: A Paradigm for the Impact of Drug Transporters on Metabolic Pathways, Signaling, and Disease.
PMID: 29309257
Annu Rev Pharmacol Toxicol · 2018
1.00
2
PCK1 and SLC22A2 gene variants associated with response to metformin treatment in type 2 diabetes.
PMID: 39928707
PLoS One · 2025
0.90
3
Promoter haplotype structure of solute carrier 22 member 2 (SLC22A2) in the Xhosa population of South Africa and their differential effect on gene expression.
PMID: 35143948
Gene · 2022
0.80
4
Organic Cation Transporter 2 (OCT2/SLC22A2) Gene Variation in the South African Bantu-Speaking Population and Functional Promoter Variants.
PMID: 28253084
OMICS · 2017
0.70
5
Both carvedilol and cimetidine alleviate cisplatin-induced nephrotoxicity via downregulating OCT2.
PMID: 40044066
Biochim Biophys Acta Mol Basis Dis · 2025
0.60