SLC22A8

Chr 11

solute carrier family 22 member 8

Also known as: OAT3

NCBI Gene: 9376ENSG00000149452UniProt: Q8TCC7

This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

84
ClinVar variants
10
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SLC22A8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 64 VUS of 84 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 1.05
OE 0.75 (0.51–1.15)
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.
0.97Z-score
OE missense 0.85 (0.77–0.94)
276 obs / 325.3 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.0.75 (0.51–1.15)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.77–0.94)
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.0.93
0≤1.21.6
LoF obs/exp: 16 / 21.2Missense obs/exp: 276 / 325.3Syn Z: 0.68

ClinVar Variant Classifications

84 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic4
VUS64
Likely Benign7
Benign3
6
Pathogenic
4
Likely Pathogenic
64
VUS
7
Likely Benign
3
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
0
56
8
0
64
Likely Benign
0
6
0
1
7
Benign
0
2
0
1
3
Total06418284

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

View in ClinVar →

Protein Context — Lollipop Plot

SLC22A8 · 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
Acid sphingomyelinase activity suggests a new antipsychotic pharmaco-treatment strategy for schizophrenia.
Chestnykh D et al.·Mol Psychiatry
2025
Transporter biology in drug approval: regulatory aspects.
Maeda K et al.·Mol Aspects Med
2013Review
Methotrexate Disposition in Pediatric Patients with Acute Lymphoblastic Leukemia: What Have We Learnt From the Genetic Variants of Drug Transporters.
Hu YH et al.·Curr Pharm Des
2019Review
Sodium-Glucose Cotransporter 2 (SGLT2) as a Potential Biomarker and Target in Papillary Renal Cell Carcinoma.
Akkus E et al.·Clin Genitourin Cancer
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
The human organic anion transporter 3 (OAT3; SLC22A8): genetic variation and functional genomics.
Erdman AR et al.·Am J Physiol Renal Physiol
2006Functional
Reduced renal clearance of cefotaxime in asians with a low-frequency polymorphism of OAT3 (SLC22A8).
Yee SW et al.·J Pharm Sci
2013
An Amish founder population reveals rare-population genetic determinants of the human lipidome.
Montasser ME et al.·Commun Biol
2022
Preclinical and clinical evidence for the collaborative transport and renal secretion of an oxazolidinone antibiotic by organic anion transporter 3 (OAT3/SLC22A8) and multidrug and toxin extrusion protein 1 (MATE1/SLC47A1).
Lai Y et al.·J Pharmacol Exp Ther
2010
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
Critical role of Slc22a8 in maintaining blood-brain barrier integrity after experimental cerebral ischemia-reperfusion.
Liu Y et al.·J Cereb Blood Flow Metab
2025
SLC22A8: An indicator for tumor immune microenvironment and prognosis of ccRCC from a comprehensive analysis of bioinformatics.
Xu K et al.·Medicine (Baltimore)
2022🔓 Open Access
Functional Characterization of Rare Variants in OAT1/SLC22A6 and OAT3/SLC22A8 Urate Transporters Identified in a Gout and Hyperuricemia Cohort.
Vávra J et al.·Cells
2022🔓 Open AccessCohort
Drug Clearance from Cerebrospinal Fluid Mediated by Organic Anion Transporters 1 (Slc22a6) and 3 (Slc22a8) at Arachnoid Membrane of Rats.
Zhang Z et al.·Mol Pharm
2018
The drug transporter OAT3 (SLC22A8) and endogenous metabolite communication via the gut-liver-kidney axis.
Bush KT et al.·J Biol Chem
2017
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