SLC22A1

Chr 6

solute carrier family 22 member 1

Also known as: HOCT1, OCT1, oct1_cds

NCBI Gene: 6580ENSG00000175003UniProt: O15245

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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [provided by RefSeq, Jul 2008]

122
ClinVar variants
25
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— SLC22A1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
25 Pathogenic / Likely Pathogenic· 83 VUS of 122 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
1.67LOEUF
pLI 0.000
Z-score -1.09
OE 1.24 (0.93–1.67)
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.
-0.09Z-score
OE missense 1.01 (0.93–1.11)
339 obs / 334.1 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.1.24 (0.93–1.67)
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 (0.93–1.11)
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.1.07
0≤1.21.6
LoF obs/exp: 30 / 24.2Missense obs/exp: 339 / 334.1Syn Z: -0.65

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic24
Likely Pathogenic1
VUS83
Likely Benign6
Benign8
24
Pathogenic
1
Likely Pathogenic
83
VUS
6
Likely Benign
8
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
78
5
0
83
Likely Benign
0
5
0
1
6
Benign
1
3
1
3
8
Total186314122

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A1 · 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
Impact of SLC22A1 and CYP3A5 genotypes on imatinib response in chronic myeloid leukemia: A systematic review and meta-analysis.
Cargnin S et al.·Pharmacol Res
2018Meta-analysis
ACE2 negatively regulates the Warburg effect and suppresses hepatocellular carcinoma progression via reducing ROS-HIF1α activity.
Dong F et al.·Int J Biol Sci
2023
ABCB1, SLC22A1, COMT, and OPRM1 genotypes: Study of their influence on plasma methadone levels and clinical response to methadone maintenance treatment in opioid use disorder.
Ait Tayeb AEK et al.·Fundam Clin Pharmacol
2025
Role of SLC22A1 polymorphic variants in drug disposition, therapeutic responses, and drug-drug interactions.
Arimany-Nardi C et al.·Pharmacogenomics J
2015Review
The influence of metformin transporter gene SLC22A1 and SLC47A1 variants on steady-state pharmacokinetics and glycemic response.
Ningrum VDA et al.·PLoS One
2022
Fine Mapping and Functional Analysis Reveal a Role of SLC22A1 in Acylcarnitine Transport.
Kim HI et al.·Am J Hum Genet
2017Functional
Genetic and Epigenetic Regulation of Organic Cation Transporters.
Kölz C et al.·Handb Exp Pharmacol
2021Review
The Role of SLC22A1 and Genomic Ancestry on Toxicity during Treatment in Children with Acute Lymphoblastic Leukemia of the Amazon Region.
Fernandes SSM et al.·Genes (Basel)
2022
Atypical Substrates of the Organic Cation Transporter 1.
Redeker KM et al.·Biomolecules
2022
Metformin transporter pharmacogenomics: insights into drug disposition-where are we now?
Chan P et al.·Expert Opin Drug Metab Toxicol
2018Review
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
Frequency of Polymorphisms in SLC47A1 (rs2252281 and rs2289669) and SLC47A2 (rs34834489 and rs12943590) and the Influence of SLC22A1 (rs72552763 and rs622342) on HbA1c Levels in Mexican-Mestizo Patients with DMT2 Treated with Metformin Monotherapy.
Gómez-Hernández MA et al.·Int J Mol Sci
2025🔓 Open AccessCohort
SLC22A1 Resists Hepatitis B Virus by Activating the JAK/STAT Pathway and Predicts the Effect of Pegylated Interferon α-Based Therapy on Chronic Hepatitis B.
Yu H et al.·J Infect 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
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Polycystic Ovary SyndromeMetformin

Metabolic Responses of Metformin and Genetic Polymorphisms of SLC22A1 Gene in PCOS

ACTIVE NOT RECRUITING
NCT05680805Phase PHASE4Bangabandhu Sheikh Mujib Medical University, Dhaka, BangladeshStarted 2023-05-27
Metformin Hydrochloride

External Resources

Links to major genomics databases and tools