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Atlas / Gene / SLC22A8

SLC22A8

gene
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Also known as OAT3

Summary

SLC22A8 (solute carrier family 22 member 8, HGNC:10972) is a protein-coding gene on chromosome 11q12.3, encoding Organic anion transporter 3 (Q8TCC7). Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient.

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.

Source: NCBI Gene 9376 — RefSeq curated summary.

At a glance

  • GWAS associations: 4
  • Clinical variants (ClinVar): 67 total
  • Druggable target: yes — 22 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_004254

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:10972
Approved symbolSLC22A8
Namesolute carrier family 22 member 8
Location11q12.3
Locus typegene with protein product
StatusApproved
AliasesOAT3
Ensembl geneENSG00000149452
Ensembl biotypeprotein_coding
OMIM607581
Entrez9376

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 7 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000311438, ENST00000336232, ENST00000430500, ENST00000451262, ENST00000535878, ENST00000539841, ENST00000542795, ENST00000542904, ENST00000544707, ENST00000545207, ENST00000886052, ENST00000946794

RefSeq mRNA: 4 — MANE Select: NM_004254 NM_001184732, NM_001184733, NM_001184736, NM_004254

CCDS: CCDS53643, CCDS53644, CCDS8042

Canonical transcript exons

ENST00000336232 — 11 exons

ExonStartEnd
ENSE000007253926299570462995819
ENSE000007254066299377062993878
ENSE000011410006299342462993627
ENSE000013261166299454262994756
ENSE000013502776299602962996152
ENSE000013503236301462663014983
ENSE000022255306299282462993336
ENSE000036333736299892162999089
ENSE000036528796300072063000823
ENSE000036746916299968862999842
ENSE000038448826301572963015841

Expression profiles

Bgee: expression breadth broad, 80 present calls, max score 96.84.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.8263 / max 685.1718, expressed in 67 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1202731.169647
1202720.656758

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
pigmented layer of retinaUBERON:000178296.84gold quality
adult organismUBERON:000702396.38gold quality
adult mammalian kidneyUBERON:000008294.39gold quality
kidney epitheliumUBERON:000481987.92gold quality
kidneyUBERON:000211387.82gold quality
nephron tubuleUBERON:000123185.90gold quality
metanephric glomerulusUBERON:000473683.63gold quality
renal glomerulusUBERON:000007482.73gold quality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047382.38gold quality
renal medullaUBERON:000036281.72gold quality
cortex of kidneyUBERON:000122580.26gold quality
olfactory bulbUBERON:000226479.07gold quality
diaphragmUBERON:000110378.24gold quality
type B pancreatic cellCL:000016977.66gold quality
metanephrosUBERON:000008176.60gold quality
vastus lateralisUBERON:000137975.05gold quality
skeletal muscle tissue of rectus abdominisUBERON:000451174.75gold quality
quadriceps femorisUBERON:000137773.77gold quality
hair follicleUBERON:000207373.34gold quality
skeletal muscle tissue of biceps brachiiUBERON:000450273.12gold quality
parotid glandUBERON:000183171.16gold quality
myocardiumUBERON:000234970.08gold quality
metanephros cortexUBERON:001053369.37gold quality
vena cavaUBERON:000408769.22silver quality
epithelial cell of pancreasCL:000008368.84gold quality
left ventricle myocardiumUBERON:000656668.62gold quality
cardiac muscle of right atriumUBERON:000337968.60gold quality
superficial temporal arteryUBERON:000161468.51gold quality
triceps brachiiUBERON:000150968.36gold quality
biceps brachiiUBERON:000150768.29gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

ExperimentMarker?Max mean expression
E-GEOD-135922yes16.26
E-ANND-3no0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF1, BCL6, CREB1, FOXC1, HNF1A, HNF1B, HNF4A

miRNA regulators (miRDB)

31 targeting SLC22A8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-4725-3P99.9669.532520
HSA-MIR-6780B-5P99.9669.602562
HSA-MIR-6721-5P99.9368.922981
HSA-MIR-427199.8868.322244
HSA-MIR-6780A-5P99.8866.692776
HSA-MIR-444799.8567.812900
HSA-MIR-1273H-5P99.7766.322471
HSA-MIR-30B-3P99.7065.762325
HSA-MIR-3689A-3P99.7065.732306
HSA-MIR-3689B-3P99.7065.712311
HSA-MIR-3689C99.7065.712311
HSA-MIR-6779-5P99.7065.762363
HSA-MIR-6861-3P99.6068.46444
HSA-MIR-613299.6065.831554
HSA-MIR-6836-5P99.6065.621538
HSA-MIR-1207-5P99.4969.112983
HSA-MIR-127599.4767.902749
HSA-MIR-18A-5P99.2971.05806
HSA-MIR-18B-5P99.2971.05806
HSA-MIR-4763-3P99.1067.832649
HSA-MIR-66199.0965.942062
HSA-MIR-1199-5P98.4466.51829
HSA-MIR-6751-3P98.4466.35835
HSA-MIR-1233-5P98.1966.711201
HSA-MIR-6778-5P98.1966.591239
HSA-MIR-443297.8067.87705
HSA-MIR-445697.5064.881678
HSA-MIR-606997.4565.88357
HSA-MIR-453597.2765.17469
HSA-MIR-426496.3564.761480

Literature-anchored findings (GeneRIF, showing 38)

  • elucidation of the molecular mechanism for renal tetracycline transport by human organic anion transporters (hOATs) using proximal tubular cells stably expressing hOATs (PMID:11855680)
  • polymorphisms in the OAT3 gene did not appear to be associated with changes in renal and tubular secretory clearance of pravastatin (PMID:12811365)
  • OAT3 plays an important role for anionic drug secretion in patients with renal diseases; expression levels of drug transporters such as OAT3 may be related to the alteration of renal drug secretion. (PMID:14984259)
  • data suggest that genetic variation in OAT3 may contribute to variation in the disposition of drugs (PMID:16291576)
  • The clustering of OAT genes in the genome raises the possibility that nucleotide polymorphisms in SLC22A6 could also effect SLC22A8 expression, and vice versa. (PMID:16648942)
  • These results indicate that the tissue-specific expression of hOAT3 might be regulated by the concerted effect of genetic (HNF1alpha and HNF1beta) and epigenetic (DNA methylation) factors. (PMID:16793932)
  • Both hOAT1 and hOAT3 are responsible for the basolateral uptake of edaravone sulfate in the kidney. (PMID:17502342)
  • urinary excretion of topotecan hydroxyl acid is accounted for by transport via OAT3, as well as glomerular filtration, in both rats and humans (PMID:17556638)
  • Inhibition of renal uptake (via OAT3) and efflux processes (via MRP2 and MRP4) explains the possible sites of drug-drug interaction for methotrexate with probenecid and some NSAIDs, including their glucuronides. (PMID:17578901)
  • hOAT3 contributes to the renal uptake of rosuvastatin (PMID:17585018)
  • The five regulatory single nucleotide polymorphism(SNP)s of OAT3 identified in nephrectomized patients are unlikely to influence OAT3 mRNA expression or promoter activity. (PMID:18414781)
  • The renal expression of OAT1 and OAT3 should be taken into account in order to improve pharmacotherapeutic efficacy and to prevent drug toxicity during the onset of this hepatic disease. (PMID:19034961)
  • Angiotensin II inhibited hOAT3 activity through the activation of PKCalpha, which led to an acceleration of hOAT3 endocytosis. (PMID:19878671)
  • Interaction of human OAT3 with 2,3-dimercapto-1-propanesulfonic acid (DMPS) determines the effect of human OAT3 on basolateral DMPS uptake in rabbit renal proximal tubules. (PMID:20237588)
  • Intergenic polymorphism rs10792367 between OAT1 and OAT3 is not associated with hypertension, but appears to be involved in between-individual variations in antihypertensive responses to hydrochlorothiazide. (PMID:21164499)
  • The data 1) reveal alpha-ketoglutarate as a common high-affinity substrate of NaDC3, OAT1, and OAT3 (PMID:21865262)
  • High urine OAT1, OAT3 and OAT4 is associated with severe acute kidney injury. (PMID:21945944)
  • Both hOAT1 and hOAT3 markedly stimulated the uptake of kynurenic acid into oocytes. (PMID:22108572)
  • The results confirmed that OAT1, OAT3, OCT2, MATE1, and MATE2-K were coexpressed in tubular epithelial cells. (PMID:23630107)
  • In HEK293-Flp-In cells, the OAT3-Ile305Phe variant had a lower maximum cefotaxime transport activity, Vmax , [159 +/- 3 nmol*(mg protein)(-1) /min (mean +/- SD)] compared with the reference OAT3 [305 +/- 28 nmol*(mg protein)(-1) /min, (mean +/- SD), p < 0.01]. (PMID:23649425)
  • transport of xanthurenic acid by OAT1 and OAT3 (PMID:23832370)
  • Pemetrexed is a superior substrate to methotrexate for hOAT3. (PMID:24042472)
  • high capacity p-cresyl sulfate trasnporter (PMID:24185403)
  • PPIs inhibit [(3)H]MTX transport via hOAT3 inhibition. (PMID:25239859)
  • The high efficacy of bendamustine in treating chronic lymphocytic leukemia might be partly due to the expression of OAT3 in lymphoma cells and the high affinity of bendamustine for this transporter. (PMID:25477469)
  • The putative promoter sequences from hOAT1 (SLC22A6) and hOAT3 (SCL22A8) were cloned into a reporter plasmid. (PMID:26277839)
  • SLC22A8 variants were not significantly associated with hyperuricemia and gout in a New Zealand Maori and Pacific cohort. (PMID:28371506)
  • Uremic toxins, p-cresyl sulfate and indoxyl sulfate, are transported into endothelial cells by OAT1/OAT3. (PMID:28472795)
  • Sgk1 stimulated OAT3 transport activity by interfering with the inhibitory effect of Nedd4-2 on the transporter. This study provides important insights into how OAT3-mediated drug elimination is regulated in vivo. (PMID:28608480)
  • Endogenous metabolite-mediated communication between OAT1/OAT3 and OATP1B1 may explain the association between SLCO1B1 SNPs and methotrexate toxicity. (PMID:29285751)
  • is richly expressed in the kidney, where it plays critical roles in the secretion, from the blood to urine, of clinically important drugs. (PMID:29422382)
  • results indicate an increased alpha-ketoglutarate efflux by OAT1 and OAT3, resulting in a metabolic shift towards an oxidative phenotype (PMID:30653465)
  • Study demonstrated for the first time that PKA stimulated OAT3 expression and transport activity by altering the trafficking kinetics of OAT3 possibly through the crosstalk between SUMOylation and ubiquitination. OAT3 is subjected to post-translational modification by SUMO-2 and SUMO-3 not by SUMO-1. (PMID:30761470)
  • these results provided first demonstration that Senp2 is a significant regulator for OAT3-mediated organic anion/drug transport (PMID:31054272)
  • Coadministration of vindesine with high-dose methotrexate therapy increases acute kidney injury via BCRP, MRP2, and OAT1/OAT3. (PMID:31691080)
  • Investigation of the arcane inhibition of human organic anion transporter 3 by benzofuran antiarrhythmic agents. (PMID:33836300)
  • Functional Characterization of Rare Variants in OAT1/SLC22A6 and OAT3/SLC22A8 Urate Transporters Identified in a Gout and Hyperuricemia Cohort. (PMID:35406626)
  • Drug transporters OAT1 and OAT3 have specific effects on multiple organs and gut microbiome as revealed by contextualized metabolic network reconstructions. (PMID:36316339)

Cross-species orthologs

43 orthologs

OrganismSymbolGene ID
danio_rerioslc22a6lENSDARG00000055523
mus_musculusSlc22a8ENSMUSG00000063796
rattus_norvegicusSlc22a8ENSRNOG00000018086
drosophila_melanogasterOrctFBGN0019952
drosophila_melanogasterCG15221FBGN0030331
drosophila_melanogasterBalatFBGN0033778
drosophila_melanogasterCG5592FBGN0035645
drosophila_melanogasterCG10486FBGN0035647
drosophila_melanogasterCG14691FBGN0037829
drosophila_melanogasterCG14855FBGN0038260
drosophila_melanogasterCG14856FBGN0038261
drosophila_melanogasterCG14857FBGN0038262
drosophila_melanogasterCG12783FBGN0038448
drosophila_melanogasterCG7333FBGN0038715
drosophila_melanogasterCG7342FBGN0038716
drosophila_melanogasterCG17751FBGN0038717
drosophila_melanogasterCG17752FBGN0038718
drosophila_melanogasterCG16727FBGN0038719
drosophila_melanogasterCG6231FBGN0038720
drosophila_melanogasterCG4465FBGN0038750
drosophila_melanogasterCG4462FBGN0038752
drosophila_melanogasterCG4459FBGN0038753
drosophila_melanogasterCG6356FBGN0039178
drosophila_melanogasterCG3690FBGN0040350
drosophila_melanogasterCG31103FBGN0051103
drosophila_melanogasterCG31106FBGN0051106
drosophila_melanogasterCG31272FBGN0051272
drosophila_melanogasterCG33233FBGN0053233
drosophila_melanogasterCG33234FBGN0053234
drosophila_melanogasterOrct2FBGN0086365
drosophila_melanogasterCG42269FBGN0259164
drosophila_melanogasterCG44098FBGN0264907
caenorhabditis_elegansWBGENE00003837
caenorhabditis_elegansoct-1WBGENE00003842
caenorhabditis_elegansWBGENE00003843
caenorhabditis_elegansWBGENE00006220
caenorhabditis_elegansWBGENE00008110
caenorhabditis_elegansWBGENE00011456
caenorhabditis_elegansWBGENE00014127
caenorhabditis_elegansWBGENE00017751
caenorhabditis_elegansWBGENE00019408
caenorhabditis_elegansWBGENE00020701
caenorhabditis_elegansWBGENE00044455

Paralogs (22): SLC22A16 (ENSG00000004809), SLC22A17 (ENSG00000092096), SLC22A2 (ENSG00000112499), SLC22A7 (ENSG00000137204), SLC22A23 (ENSG00000137266), SLC22A14 (ENSG00000144671), SLC22A3 (ENSG00000146477), SLC22A9 (ENSG00000149742), SVOPL (ENSG00000157703), SLC22A15 (ENSG00000163393), SVOP (ENSG00000166111), SLC22A11 (ENSG00000168065), SLC22A13 (ENSG00000172940), SLC22A1 (ENSG00000175003), SLC22A10 (ENSG00000184999), SLC22A25 (ENSG00000196600), SLC22A4 (ENSG00000197208), SLC22A5 (ENSG00000197375), SLC22A24 (ENSG00000197658), SLC22A12 (ENSG00000197891), SLC22A6 (ENSG00000197901), SLC22A31 (ENSG00000259803)

Protein

Protein identifiers

Organic anion transporter 3 — Q8TCC7 (reviewed: Q8TCC7)

Alternative names: Organic anion/dicarboxylate exchanger, Solute carrier family 22 member 8

All UniProt accessions (2): Q8TCC7, H7BXN9

UniProt curated annotations — full annotation on UniProt →

Function. Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient. Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate). Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain. E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange. Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule. Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate. Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins. May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside. May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate. Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor). May contribute to the release of cortisol in the adrenals. Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile. Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB). In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body.

Subcellular location. Basolateral cell membrane.

Tissue specificity. Strongly expressed in kidney. Weaker expression in brain and skeletal muscle. Expressed in adrenal glands.

Similarity. Belongs to the major facilitator (TC 2.A.1) superfamily. Organic cation transporter (TC 2.A.1.19) family.

Isoforms (5)

UniProt IDNamesCanonical?
Q8TCC7-11yes
Q8TCC7-22
Q8TCC7-55
Q8TCC7-33
Q8TCC7-44

RefSeq proteins (4): NP_001171661, NP_001171662, NP_001171665, NP_004245* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR004749Orgcat_transp/SVOPFamily
IPR005828MFS_sugar_transport-likeFamily
IPR005829Sugar_transporter_CSConserved_site
IPR020846MFS_domDomain
IPR036259MFS_trans_sfHomologous_superfamily

Pfam: PF00083

Catalyzed reactions (Rhea), 12 shown:

  • glutarate(in) + 2-oxoglutarate(out) = glutarate(out) + 2-oxoglutarate(in) (RHEA:71751)
  • estrone 3-sulfate(out) + glutarate(in) = estrone 3-sulfate(in) + glutarate(out) (RHEA:72151)
  • taurocholate(out) + glutarate(in) = taurocholate(in) + glutarate(out) (RHEA:72159)
  • dehydroepiandrosterone 3-sulfate(out) + glutarate(in) = dehydroepiandrosterone 3-sulfate(in) + glutarate(out) (RHEA:72355)
  • estrone 3-sulfate(in) + 2-oxoglutarate(out) = estrone 3-sulfate(out) + 2-oxoglutarate(in) (RHEA:72399)
  • urate(in) + 2-oxoglutarate(out) = urate(out) + 2-oxoglutarate(in) (RHEA:72403)
  • prostaglandin E2(out) + glutarate(in) = prostaglandin E2(in) + glutarate(out) (RHEA:72495)
  • prostaglandin E2(out) + 2-oxoglutarate(in) = prostaglandin E2(in) + 2-oxoglutarate(out) (RHEA:72499)
  • prostaglandin F2alpha(out) + glutarate(in) = prostaglandin F2alpha(in) + glutarate(out) (RHEA:72503)
  • prostaglandin F2alpha(out) + 2-oxoglutarate(in) = prostaglandin F2alpha(in) + 2-oxoglutarate(out) (RHEA:72507)
  • (R)-carnitine(out) + 2-oxoglutarate(in) = (R)-carnitine(in) + 2-oxoglutarate(out) (RHEA:72511)
  • glutarate(in) + (R)-carnitine(out) = glutarate(out) + (R)-carnitine(in) (RHEA:72515)

UniProt features (50 total): topological domain 12, transmembrane region 11, sequence variant 8, sequence conflict 7, splice variant 6, glycosylation site 2, chain 1, region of interest 1, compositionally biased region 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q8TCC7-F186.110.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 4

Glycosylation sites (2): 86, 102

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

IDPathway
R-HSA-561048Organic anion transport by SLC22 transporters
R-HSA-9793528Ciprofloxacin ADME
R-HSA-382551Transport of small molecules
R-HSA-425366
R-HSA-425407SLC-mediated transmembrane transport
R-HSA-549132
R-HSA-9748784Drug ADME

MSigDB gene sets: 84 (showing top): WWTAAGGC_UNKNOWN, GOBP_CIRCULATORY_SYSTEM_PROCESS, EFC_Q6, GOBP_ORGANIC_ACID_TRANSPORT, TCF4_Q5, RYTAAWNNNTGAY_UNKNOWN, GOBP_ORGANIC_ANION_TRANSPORT, GOBP_MONOCARBOXYLIC_ACID_TRANSPORT, GOCC_APICAL_PLASMA_MEMBRANE, HNF1_C, TGGNNNNNNKCCAR_UNKNOWN, LEF1_Q6, GOBP_RESPONSE_TO_TOXIC_SUBSTANCE, MODULE_48, GOBP_LIPID_LOCALIZATION

GO Biological Process (9): monoatomic ion transport (GO:0006811), response to toxic substance (GO:0009636), obsolete organic anion transport (GO:0015711), prostaglandin transport (GO:0015732), transport across blood-brain barrier (GO:0150104), lipid transport (GO:0006869), inorganic anion transport (GO:0015698), xenobiotic transport (GO:0042908), transmembrane transport (GO:0055085)

GO Molecular Function (6): solute:inorganic anion antiporter activity (GO:0005452), obsolete organic anion transmembrane transporter activity (GO:0008514), prostaglandin transmembrane transporter activity (GO:0015132), xenobiotic transmembrane transporter activity (GO:0042910), antiporter activity (GO:0015297), transmembrane transporter activity (GO:0022857)

GO Cellular Component (6): plasma membrane (GO:0005886), basolateral plasma membrane (GO:0016323), apical plasma membrane (GO:0016324), extracellular exosome (GO:0070062), basal plasma membrane (GO:0009925), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

CategoryPathways
SLC-mediated transport of organic anions1
Drug ADME1
Transport of small molecules1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
transport5
plasma membrane region3
response to chemical1
fatty acid transport1
icosanoid transport1
vascular transport1
lipid localization1
cellular process1
antiporter activity1
prostaglandin transport1
icosanoid transmembrane transporter activity1
transmembrane transporter activity1
xenobiotic transport1
secondary active transmembrane transporter activity1
transporter activity1
transmembrane transport1
membrane1
cell periphery1
basal plasma membrane1
apical part of cell1
extracellular vesicle1
basal part of cell1
cellular anatomical structure1

Protein interactions and networks

STRING

1218 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
SLC22A8ABCC2Q92887903
SLC22A8SLCO1B3Q9NPD5845
SLC22A8SLCO1B1Q9Y6L6827
SLC22A8SLC47A2Q86VL8822
SLC22A8SLC47A1Q96FL8802
SLC22A8ABCC4O15439797
SLC22A8ABCG2Q9UNQ0796
SLC22A8ABCA8O94911785
SLC22A8SLC2A9Q9NRM0776
SLC22A8SLCO1A2P46721776
SLC22A8SLCO2B1O94956769
SLC22A8SLCO4C1Q6ZQN7722
SLC22A8SLC17A3O00476674
SLC22A8SLC15A2Q16348670
SLC22A8SLC17A1Q14916650

IntAct

7 interactions, top by confidence:

ABTypeScore
SLC22A8HSPA5psi-mi:“MI:0915”(physical association)0.400
SLC22A8HNRNPCL2psi-mi:“MI:0915”(physical association)0.400
Mpsi-mi:“MI:0914”(association)0.350
SLC22A8HLA-Cpsi-mi:“MI:0914”(association)0.350
SLC22A8HLA-Epsi-mi:“MI:0914”(association)0.350
SLC22A8psi-mi:“MI:0915”(physical association)0.000

BioGRID (33): NEDD4L (Affinity Capture-Western), NEDD4 (Affinity Capture-Western), SLC22A8 (Proximity Label-MS), SLC22A8 (Proximity Label-MS), SAMM50 (Affinity Capture-MS), SLC25A46 (Affinity Capture-MS), ORMDL1 (Affinity Capture-MS), TMUB2 (Affinity Capture-MS), MTFP1 (Affinity Capture-MS), HLA-C (Affinity Capture-MS), MTX3 (Affinity Capture-MS), EPHA5 (Affinity Capture-MS), ABHD17B (Affinity Capture-MS), NOMO1 (Affinity Capture-MS), GK (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2IDB4, A0A8B7HA97, A4ZYQ5, A6NK97, G1SZD9, O35956, O57379, O88909, P22732, P23945, P43427, Q0IHM1, Q2KIV1, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R9C4, Q5RC45, Q5RCH6, Q5RET7, Q63ZE4, Q66J52, Q6DFR1, Q6NUB3, Q6NYN7, Q6PXP3, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q863Y9, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48, Q8N4F4, Q8R0S9

Diamond homologs: A0A3Q2IDB4, A0A8B7HA97, A6NK97, A6QLW8, B2GV36, G1SZD9, O34691, O35956, O57379, O75751, O88446, O88909, Q1RPP5, Q28ES4, Q2KIV1, Q3YAW7, Q3ZAV1, Q4U2R8, Q4W8A2, Q4W8A3, Q5R540, Q5R9C4, Q5RC45, Q5RCH6, Q5RLM2, Q63ZE4, Q66J52, Q66J54, Q6A4L0, Q6NYN7, Q6T423, Q70BM6, Q76M72, Q76M99, Q80UJ1, Q864Z3, Q8CFZ5, Q8HY24, Q8IVM8, Q8MK48

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

67 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance57
Likely benign7
Benign3

Top pathogenic / likely-pathogenic (0)

SpliceAI

1791 predictions. Top by Δscore:

VariantEffectΔscore
11:62993628:C:CCacceptor_gain1.0000
11:62993766:CTA:Cdonor_loss1.0000
11:62993767:TA:Tdonor_loss1.0000
11:62993768:A:AGdonor_loss1.0000
11:62993769:CCT:Cdonor_loss1.0000
11:62993874:CAAGT:Cacceptor_gain1.0000
11:62993876:AGT:Aacceptor_gain1.0000
11:62993877:GT:Gacceptor_gain1.0000
11:62993877:GTC:Gacceptor_loss1.0000
11:62993878:TC:Tacceptor_loss1.0000
11:62993879:C:CCacceptor_gain1.0000
11:62993879:CTG:Cacceptor_loss1.0000
11:62994576:T:TAdonor_gain1.0000
11:62994624:G:Cdonor_gain1.0000
11:62996054:T:TAdonor_gain1.0000
11:62998964:A:Cdonor_gain1.0000
11:62999686:A:ACdonor_gain1.0000
11:62999687:C:CCdonor_gain1.0000
11:62999687:CT:Cdonor_gain1.0000
11:62993623:TTTGC:Tacceptor_gain0.9900
11:62993625:TGC:Tacceptor_gain0.9900
11:62993628:CT:Cacceptor_loss0.9900
11:62993768:A:ACdonor_gain0.9900
11:62993769:C:CCdonor_gain0.9900
11:62993875:AAGT:Aacceptor_gain0.9900
11:62994628:A:ACdonor_gain0.9900
11:62994755:ACCTG:Aacceptor_loss0.9900
11:62994758:T:Gacceptor_loss0.9900
11:62995698:GGTTA:Gdonor_loss0.9900
11:62995699:GTTA:Gdonor_loss0.9900

AlphaMissense

3526 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
11:62998977:C:AW235C0.992
11:62998977:C:GW235C0.992
11:63014839:G:CF40L0.990
11:63014839:G:TF40L0.990
11:63014841:A:GF40L0.990
11:63014813:C:GC49S0.989
11:63014814:A:TC49S0.989
11:62993582:G:CS457R0.985
11:62993582:G:TS457R0.985
11:62993584:T:GS457R0.985
11:62998979:A:GW235R0.985
11:62998979:A:TW235R0.985
11:62999020:C:TG221D0.985
11:62999729:C:TG184D0.985
11:62999741:C:GR180P0.985
11:62999770:G:CS170R0.985
11:62999770:G:TS170R0.985
11:62999772:T:GS170R0.985
11:63000762:C:TG132D0.985
11:62993838:C:AK419N0.984
11:62993838:C:GK419N0.984
11:63000821:C:AW112C0.984
11:63000821:C:GW112C0.984
11:62993496:C:TG486D0.983
11:63014662:C:AW99C0.983
11:63014662:C:GW99C0.983
11:62993586:C:TG456E0.982
11:63000810:C:GC116S0.982
11:63000811:A:TC116S0.982
11:62993517:C:TG479E0.981

dbSNP variants (sampled 300 via entrez): RS1000192624 (11:63005576 T>C), RS1000234719 (11:63017156 T>C), RS1000242749 (11:63010530 C>A), RS1000358390 (11:63010288 C>T), RS1000396503 (11:63010800 C>T), RS1000417980 (11:63016362 TCCCTGAG>T), RS1000713569 (11:62996824 A>G), RS1000784879 (11:63003619 A>G,T), RS1000872009 (11:63016638 G>A), RS1000941300 (11:62999200 A>C,T), RS1001211991 (11:62998856 T>C,G), RS1001576592 (11:63009752 G>A), RS1001577262 (11:63011904 T>G), RS1001694738 (11:63005444 C>A), RS1001746413 (11:62998656 C>A)

Disease associations

OMIM: gene MIM:607581 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

StudyTraitp-value
GCST001525_4Visceral fat5.000000e-06
GCST006817_1Response to antidepressants in depression2.000000e-06
GCST010512_7Serum uric acid levels1.000000e-08
GCST012020_434Serum metabolite levels5.000000e-39

EFO canonical traits (1, from GWAS)

EFO IDTrait name
EFO:0004761uric acid measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1641348 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

22 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 842,043 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL101PHENYLBUTAZONE459,455
CHEMBL1144PRAVASTATIN470,953
CHEMBL1146CEFAMANDOLE421,886
CHEMBL1435CEFAZOLIN437,670
CHEMBL161CEFTRIAXONE471,135
CHEMBL1644CEFADROXIL46,102
CHEMBL1730CEFOTAXIME4480
CHEMBL29PENICILLIN G456,772
CHEMBL30CIMETIDINE447,191
CHEMBL316157CEPHALORIDINE445,474
CHEMBL463AMINOHIPPURIC ACID42,260
CHEMBL507674CEFOPERAZONE423,712
CHEMBL527PIROXICAM4107,554
CHEMBL6INDOMETHACIN4156,366
CHEMBL617CEPHALOTHIN424,927
CHEMBL897PROBENECID4105,640
CHEMBL4112930PAMIPARIB32,114
CHEMBL52333ROLOFYLLINE3421
CHEMBL119625ZONAMPANEL2209
CHEMBL1231530BETAMIPRON21,722
CHEMBL324846OCTANOIC ACID2
CHEMBL4640580EPAMINURAD1

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB clinical annotations

1 annotations.

VariantTypeLevelDrugsPhenotypes
rs11568482Metabolism/PK3cefotaxime

PharmGKB variants

2 variants.

VariantGenesLevelScore#Clin annotsDrugs
rs11568482SLC22A831.501cefotaxime
rs2276299SLC22A80.000

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: transporter — Organic anion transporters (OATs)

Most potent curated ligand interactions (2 total), top 2:

LigandActionAffinityParameter
cefalotinInhibition7.59pIC50
NPT520-34Inhibition6.6pIC50

ChEMBL bioactivities

33 potent at pChembl≥5 of 48 total, top 32 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
7.40Ki40nMCEPHALOTHIN
7.34Ki46nMCEFAMANDOLE
6.54Ki290nMCEFOTAXIME
6.30IC50500nMCHEMBL3688197
6.26Ki550nMCEFAZOLIN
6.17IC50670nMCHEMBL6143249
6.14IC50720nMCHEMBL3683287
5.96IC501100nMCHEMBL4519013
5.96IC501100nMCHEMBL4562825
5.89IC501300nMCHEMBL4584575
5.72Ki1890nMCEFOPERAZONE
5.64IC502300nMCHEMBL4527448
5.62Ki2400nMEPAMINURAD
5.61Ki2460nMCEPHALORIDINE
5.55IC502800nMCHEMBL4582456
5.48IC503300nMCHEMBL3924161
5.47IC503400nMCHEMBL3929544
5.43Ki3700nMROLOFYLLINE
5.36Ki4390nMCEFTRIAXONE
5.36Ki4410nMPROBENECID
5.31IC504930nMPROBENECID
5.31Ki4880nMPIROXICAM
5.22Ki5950nMINDOMETHACIN
5.22IC506000nMCHEMBL603656
5.19IC506500nMCHEMBL38650
5.18IC506600nMZONAMPANEL
5.08IC508300nMCHEMBL4525573
5.07Ki8600nMOCTANOIC ACID
5.06Ki8620nMCEFADROXIL
5.05Ki9000nMPROBENECID
5.05IC509000nMPROBENECID
5.00IC509920nMBETAMIPRON

PubChem BioAssay actives

28 with measured affinity, of 248 total; 24 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

CompoundAssayTypeValueUnit
(6R,7R)-3-(acetyloxymethyl)-8-oxo-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski0.0400uM
(6R,7R)-7-[[(2R)-2-hydroxy-2-phenylacetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski0.0460uM
Cefotaxime681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski0.2900uM
Cefazolin681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski0.5500uM
1-ethenyl-7-hydroxy-8-methyl-9,10-dihydrophenanthrene-2-carboxylic acid1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic501.1000uM
4-ethenyl-7-hydroxy-8-methyl-9,10-dihydrophenanthrene-2-carboxylic acid1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic501.1000uM
3-ethenyl-7-hydroxy-8-methyl-9,10-dihydrophenanthrene-2-carboxylic acid1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic501.3000uM
(6R,7R)-7-[[(2R)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-(4-hydroxyphenyl)acetyl]amino]-3-[(1-methyltetrazol-5-yl)sulfanylmethyl]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski1.8900uM
bis(4-hydroxy-3-methoxyphenyl)methanone1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic502.3000uM
(3,5-dibromo-4-hydroxyphenyl)-(2,3-dihydropyrido[4,3-b][1,4]oxazin-4-yl)methanone1649930: Inhibition of human OAT3ki2.4000uM
(6R,7R)-8-oxo-3-(pyridin-1-ium-1-ylmethyl)-7-[(2-thiophen-2-ylacetyl)amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski2.4600uM
1-ethenyl-7-hydroxy-8-methyl-9,10-dihydrophenanthrene-3-carboxylic acid1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic502.8000uM
1,3-dipropyl-8-(3-tricyclo[3.3.1.03,7]nonanyl)-7H-purine-2,6-dione678987: TP_TRANSPORTER: inhibition of E1S uptake in OAT3-expressing S2 cellski3.7000uM
Ceftriaxone681373: TP_TRANSPORTER: inhibition of Estrone sulfate uptake in OAT3-expressing S2 cellski4.3900uM
Probenecid678814: TP_TRANSPORTER: inhibition of Ochratoxin A uptake in OAT3-expressing S2 cellski4.4100uM
Piroxicam678814: TP_TRANSPORTER: inhibition of Ochratoxin A uptake in OAT3-expressing S2 cellski4.8800uM
Indomethacin681372: TP_TRANSPORTER: inhibition of MTX uptake in OAT3-expressing S2 cellski5.9500uM
4-[[5-[2-[(4-fluorophenyl)methylcarbamoyl]-6-methyl-4-pyridinyl]tetrazol-2-yl]methyl]cyclohexane-1-carboxylic acid1274680: Inhibition of human OAT3 expressed in HEK cells assessed as reduction of [3H]-estrone sulfate uptake by radioactivity counting analysisic506.0000uM
5-ethenyl-1,6-dimethyl-9,10-dihydrophenanthrene-2,7-diol1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic506.5000uM
2-(7-imidazol-1-yl-6-nitro-2,3-dioxo-4H-quinoxalin-1-yl)acetic acid496845: Inhibition of human OAT3ic506.6000uM
5-(1-methoxyethyl)-1-methyl-9,10-dihydrophenanthrene-2,7-diol1639438: Inhibition of OAT3 (unknown origin) expressed in HEK293 cells assessed as reduction in 6-CF uptake measured after 5 mins by fluorescence assayic508.3000uM
caprylic acid678814: TP_TRANSPORTER: inhibition of Ochratoxin A uptake in OAT3-expressing S2 cellski8.6000uM
Cefadroxil1209738: Inhibition of human OAT3 using estrone-3-sulfate as substrateki8.6200uM
3-benzamidopropanoic acid678815: TP_TRANSPORTER: inhibition of ES uptake (ES: 50nM) in hOAT3-expressing S2 cellsic509.9200uM

CTD chemical–gene interactions

118 total (human), top 30 by PubMed support.

ChemicalActions (top 5)PubMed papers
Probenecidincreases uptake, increases chemical synthesis, decreases activity, decreases expression, affects transport (+2 more)15
estrone sulfateincreases reaction, increases import, decreases reaction, increases uptake, affects transport (+1 more)13
p-Aminohippuric Acidaffects transport, increases uptake, increases activity, increases export, increases reaction5
Cimetidineaffects transport, decreases reaction, increases uptake4
Methotrexatedecreases reaction, increases uptake, affects transport, increases response to substance4
6-carboxyfluoresceinincreases uptake, decreases reaction, increases import, increases reaction3
Dehydroepiandrosterone Sulfateaffects transport, increases uptake3
aristolochic acid Idecreases reaction, increases uptake, increases export, increases reaction, decreases activity (+2 more)2
ochratoxin Aaffects transport, increases uptake2
4-carboxyfluoresceindecreases reaction, increases uptake, increases transport2
adefovirincreases response to substance2
5,7-dihydroxy-6-methoxy-2-phenylchromen-4-onedecreases reaction, increases uptake, decreases activity2
Tenofovirincreases import, increases response to substance2
Benzo(a)pyreneaffects methylation, decreases activity, decreases methylation, increases methylation2
Mercuryaffects abundance, affects response to substance2
Penicillin Gdecreases reaction, increases uptake2
Quercetindecreases reaction, increases uptake, decreases activity2
Famotidineaffects transport, decreases reaction, increases uptake2
5-(N-(4-((4-ethylbenzyl)thio)phenyl)sulfamoyl)-2-methylbenzoic aciddecreases activity1
aurantio-obtusindecreases activity1
bisphenol Fdecreases reaction, increases uptake, decreases activity1
methyl 2-(1-(5-fluoropentyl)-1H-indazole-3-carboxamide)-3,3-dimethylbutanoatedecreases reaction, increases uptake1
daidzeinincreases uptake1
bisphenol Adecreases reaction, increases uptake, decreases activity1
sodium arsenateincreases import, increases reaction, increases activity1
2-amino-9H-pyrido(2,3-b)indoledecreases reaction, increases import, increases reaction, decreases activity1
3-amino-1-methyl-5H-pyrido(4,3-b)indoledecreases reaction, increases import, decreases activity1
rheindecreases reaction, increases uptake1
tetrabromobisphenol Adecreases reaction, increases uptake, decreases activity1
perfluorooctanoic acidincreases uptake1

ChEMBL screening assays

110 unique, capped per target: 55 functional, 31 binding, 24 admet

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1217026BindingInhibition of human OAT3alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) antagonists: from bench to bedside. — J Med Chem
CHEMBL1743148ADMETSubstrates of transporters of clinical importance in the absorption and disposition of drugs, OAT3Membrane transporters in drug development. — Nat Rev Drug Discov
CHEMBL2075337FunctionalTP_TRANSPORTER: uptake in OAT3-expressing S2 cellsHuman organic anion transporters and human organic cation transporters mediate renal antiviral transport. — J Pharmacol Exp Ther

Cellosaurus cell lines

2 cell lines: 1 conditionally immortalized cell line, 1 telomerase immortalized cell line

First 10 cell lines (id-ordered, not curated):

CellosaurusNameCategorySex
CVCL_LI02ciPTEC-OAT3Conditionally immortalized cell lineFemale
CVCL_VR68RPTEC/TERT1 OAT3Telomerase immortalized cell lineMale

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 80

This page pulls from 80 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot