SLC22A2

Chr 6

solute carrier family 22 member 2

Also known as: OCT2

NCBI Gene: 6582ENSG00000112499UniProt: O15244

Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

90
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC22A2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 60 VUS of 90 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.15LOEUF
pLI 0.000
Z-score 0.94
OE 0.80 (0.57–1.15)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.07Z-score
OE missense 1.01 (0.92–1.10)
339 obs / 335.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.80 (0.57–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.01 (0.92–1.10)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.95
0≤1.21.6
LoF obs/exp: 21 / 26.2Missense obs/exp: 339 / 335.6Syn Z: 0.48

ClinVar Variant Classifications

90 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS60
Likely Benign4
Benign1
24
Pathogenic
1
Likely Pathogenic
60
VUS
4
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
24
0
24
Likely Pathogenic
0
0
1
0
1
VUS
0
53
7
0
60
Likely Benign
0
1
0
3
4
Benign
0
0
0
1
1
Total05432490

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetic variation on dolutegravir pharmacokinetics and relation to safety and efficacy outcomes: a systematic review.
Bevers LAH et al.·Pharmacogenomics
2024Review
The SLC22A2 gene is a determinant of hematological toxicity of oxaliplatin in patients with colorectal cancer.
Chen J et al.·Int J Clin Pharmacol Ther
2023Cohort
Pharmacogenomics in pediatric oncology patients with solid tumors related to chemotherapy-induced toxicity: A systematic review.
Hansson P et al.·Crit Rev Oncol Hematol
2025Review
Organic cation transporters 2: Structure, regulation, functions, and clinical implications.
Ailabouni A et al.·Drug Metab Dispos
2025Review
SLC22A2 variants and dolutegravir levels correlate with psychiatric symptoms in persons with HIV.
Borghetti A et al.·J Antimicrob Chemother
2019
Genetic and Epigenetic Regulation of Organic Cation Transporters.
Kölz C et al.·Handb Exp Pharmacol
2021Review
Prognostic associations of PFAS in ovarian cancer: Insights from exploratory analysis.
Xie H et al.·Ecotoxicol Environ Saf
2025
Transporter biology in drug approval: regulatory aspects.
Maeda K et al.·Mol Aspects Med
2013Review
The Effect of Genetic Variants of SLC22A2 (rs662301 and rs315978) on the response to Metformin in type 2 Saudi diabetic patients.
Alharbi AE et al.·Gene
2024Cohort
The Impact of Genetic Polymorphisms in Organic Cation Transporters on Renal Drug Disposition.
Zazuli Z et al.·Int J Mol Sci
2020Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools