SLC22A6

Chr 11

solute carrier family 22 member 6

Also known as: HOAT1, OAT1, PAHT, ROAT1

NCBI Gene: 9356ENSG00000197901UniProt: Q4U2R8

The protein encoded by this gene is involved in the sodium-dependent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and may be localized to the basolateral membrane. Four transcript variants encoding four different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

102
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC22A6
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 83 VUS of 102 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.
0.99LOEUF
pLI 0.000
Z-score 1.60
OE 0.64 (0.43–0.99)
Tolerant

Typical tolerance to LoF variation

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.
0.58Z-score
OE missense 0.91 (0.83–1.00)
305 obs / 335.0 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.0.64 (0.43–0.99)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.83–1.00)
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.0.97
0≤1.21.6
LoF obs/exp: 15 / 23.3Missense obs/exp: 305 / 335.0Syn Z: 0.24

ClinVar Variant Classifications

102 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS83
Likely Benign7
Benign1
6
Pathogenic
4
Likely Pathogenic
83
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
4
0
4
VUS
1
76
6
0
83
Likely Benign
0
4
0
3
7
Benign
0
0
0
1
1
Total180164101

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A6 · 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
SLC22A6-dependent lactylation of H3K9 aggravates endothelial dysfunction and atherosclerosis.
Ma Y et al.·Metabolism
2026
Transporter biology in drug approval: regulatory aspects.
Maeda K et al.·Mol Aspects Med
2013Review
The SLC Family Are Candidate Diagnostic and Prognostic Biomarkers in Clear Cell Renal Cell Carcinoma.
Kang W et al.·Biomed Res Int
2020
Functional analysis of polymorphisms in the organic anion transporter, SLC22A6 (OAT1).
Fujita T et al.·Pharmacogenet Genomics
2005Functional
Identification and validation of SLC16A8 as a prognostic biomarker in clear cell renal cell carcinoma: a six-gene solute carrier signature.
Wen H et al.·Exp Cell Res
2025
Potential for food-drug interactions by dietary phenolic acids on human organic anion transporters 1 (SLC22A6), 3 (SLC22A8), and 4 (SLC22A11).
Wang L et al.·Biochem Pharmacol
2012
Functional characterization and comparison of human and mouse organic anion transporter 1 as drugs and pesticides uptake carrier.
Floerl S et al.·Eur J Pharm Sci
2022Functional
Drug and toxicant handling by the OAT organic anion transporters in the kidney and other tissues.
Nigam SK et al.·Nat Clin Pract Nephrol
2007Review
Human organic anion transporters 1 (hOAT1/SLC22A6) and 3 (hOAT3/SLC22A8) transport edaravone (MCI-186; 3-methyl-1-phenyl-2-pyrazolin-5-one) and its sulfate conjugate.
Mizuno N et al.·Drug Metab Dispos
2007
A pharmacogenetic candidate gene study of tenofovir-associated Fanconi syndrome.
Dahlin A et al.·Pharmacogenet Genomics
2015
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