SLC22A3

Chr 6

solute carrier family 22 member 3

Also known as: EMT, EMTH, OCT3

NCBI Gene: 6581ENSG00000146477UniProt: O75751

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. [provided by RefSeq, Jul 2008]

106
ClinVar variants
26
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC22A3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
26 Pathogenic / Likely Pathogenic· 75 VUS of 106 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.
1.03LOEUF
pLI 0.000
Z-score 1.42
OE 0.70 (0.48–1.03)
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.
0.49Z-score
OE missense 0.92 (0.83–1.02)
279 obs / 302.8 exp
Tolerant

Mild missense constraint

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.0.70 (0.48–1.03)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.83–1.02)
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.1.04
0≤1.21.6
LoF obs/exp: 18 / 25.8Missense obs/exp: 279 / 302.8Syn Z: -0.36

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic25
Likely Pathogenic1
VUS75
Likely Benign2
Benign3
25
Pathogenic
1
Likely Pathogenic
75
VUS
2
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
25
0
25
Likely Pathogenic
0
0
1
0
1
VUS
0
68
7
0
75
Likely Benign
0
1
0
1
2
Benign
0
0
2
1
3
Total069352106

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A3 · 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
SLC22A3 methylation-mediated gene silencing predicts adverse prognosis in acute myeloid leukemia.
Gu Y et al.·Clin Epigenetics
2022
Functional Variant in the SLC22A3-LPAL2-LPA Gene Cluster Contributes to the Severity of Coronary Artery Disease.
Wang L et al.·Arterioscler Thromb Vasc Biol
2016Functional
SLC22A3 is associated with lipoprotein (a) concentration and cardiovascular disease in familial hypercholesterolemia.
Paquette M et al.·Clin Biochem
2019
Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma.
Cervenkova L et al.·Sci Rep
2019Clinical trial
SNP rs9364554 Modulates Androgen Receptor Binding and Drug Response in Prostate Cancer.
Yan Y et al.·Biomolecules
2025
A Polynesian-specific SLC22A3 variant associates with low plasma lipoprotein(a) concentrations independent of apo(a) isoform size in males.
Wang Q et al.·Biosci Rep
2024
Expression and clinical significance of organic cation transporter family in glioblastoma multiforme.
Lian Q et al.·Ir J Med Sci
2022
SLC22A3 polymorphisms do not modify pancreatic cancer risk, but may influence overall patient survival.
Mohelnikova-Duchonova B et al.·Sci Rep
2017
Genetic and Epigenetic Regulation of Organic Cation Transporters.
Kölz C et al.·Handb Exp Pharmacol
2021Review
Effect of Genetic Polymorphisms of Human SLC22A3 in the 5'-flanking Region on OCT3 Expression and Sebum Levels in Human Skin.
Takechi T et al.·J Dermatol Sci
2021
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Pharmacogenetics and Molecular Ancestry of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Ecuadorian Subjects with Type 2 Diabetes Mellitus.
Ortega-Ayala A et al.·Pharmaceuticals (Basel)
2025🔓 Open Access
Influence of Organic Cation Transporter 3 (SLC22A3) Genetic Polymorphisms on Antidepressant Maintenance Doses in Japanese Patients with Depression.
Inoue K et al.·Neuropsychobiology
2025Cohort
Unraveling the protective role of m6A methylation in SLC22A3 expression for breast Cancer intervention.
Xiao Y et al.·Biochim Biophys Acta Mol Basis Dis
2025
Molecular Ancestry Across Allelic Variants of SLC22A1, SLC22A2, SLC22A3, ABCB1, CYP2C8, CYP2C9, and CYP2C19 in Mexican-Mestizo DMT2 Patients.
Ortega-Ayala A et al.·Biomedicines
2025🔓 Open AccessCohort
Exome Sequence Data of Eight SLC Transporters Reveal That SLC22A1 and SLC22A3 Variants Alter Metformin Pharmacokinetics and Glycemic Control.
Morales-Rivera MI et al.·Pharmaceuticals (Basel)
2024🔓 Open Access
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