Affinage

Showing SLC22A12 — URAT1 is a alias.

SLC22A12

Solute carrier family 22 member 12 · UniProt Q96S37

Length
553 aa
Mass
59.6 kDa
Annotated
2026-06-10
100 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

SLC22A12 (URAT1) is the principal apical urate-anion exchanger of the renal proximal tubule and the central determinant of renal urate reabsorption (PMID:14694169, PMID:21272127). It mediates electrogenic, chloride-sensitive urate transport that is bidirectional, supporting both reabsorptive uptake and efflux, and is trans-stimulated by intracellular monocarboxylates such as lactate and pyrazinecarboxylate (PMID:21074513, PMID:21148271). Cryo-EM structures captured in inward-open, outward-open, and occluded states define the transport cycle and the binding modes of urate and uricosuric inhibitors (PMID:40169562). Beyond urate, URAT1 transports salicylate and xanthine, the latter cooperatively with GLUT9 in transcellular assays; salicylate behaves as both an exchange substrate (trans-stimulating reabsorption at low dose) and a competitive inhibitor at high dose (PMID:20560471, PMID:33132325). Transport activity is tuned post-translationally: PDZK1 binds the C-terminal PDZ motif of URAT1 to raise apical surface expression and Vmax (PMID:15304510), while AKT and high-salt-induced SGK1 phosphorylate URAT1 at Thr408 (dependent on Arg405) to increase surface abundance and activity (PMID:40100301). Loss-of-function mutations in SLC22A12 cause renal hypouricemia type 1, frequently through impaired transport or ER retention of misfolded protein (PMID:14694169, PMID:23386035). Although best characterized in kidney, URAT1 is also expressed in ependymal cilia, cardiomyocytes, liver, and brown adipose tissue, where its activity has been linked to local metabolic and inflammatory responses (PMID:24156345, PMID:34863940, PMID:37694143).

Mechanistic history

Synthesis pass · year-by-year structured walk · 10 steps
  1. 2004 High

    Establishing that URAT1 is the primary renal reabsorptive urate transporter and the in vivo target of uricosuric and anti-uricosuric drugs converted a candidate transporter into the genetic and pharmacological linchpin of urate handling.

    Evidence SLC22A12 sequencing in renal hypouricemia patients with pharmacological loading tests (probenecid, benzbromarone, pyrazinamide)

    PMID:14694169

    Open questions at the time
    • Did not resolve the exchange mechanism or counter-ion at molecular level
    • Residual reabsorption pathway not identified
  2. 2004 High

    Identifying PDZK1 as a scaffold partner answered how URAT1 is held at and enriched on the apical membrane, linking trafficking to transport capacity.

    Evidence Yeast two-hybrid, SPR, reciprocal Co-IP, colocalization, and urate transport assays in HEK293 cells

    PMID:15304510

    Open questions at the time
    • Vmax increase modest (1.4-fold); physiological magnitude in vivo unclear
    • Whether PDZK1 regulation is dynamically modulated not addressed
  3. 2004 Medium

    Mapping the promoter and showing testosterone-stimulated activity provided a transcriptional basis for sex differences in serum urate.

    Evidence Primer extension, 5'-RACE, and promoter-luciferase reporters with testosterone stimulation in OK cells

    PMID:15566944

    Open questions at the time
    • Direct transcription factor mediating testosterone response not identified
    • In vivo relevance to human sex differences not established
  4. 2010 High

    Oocyte and BBMV reconstitution defined URAT1 as a chloride-sensitive, monocarboxylate trans-stimulated urate transporter, and knockout mice confirmed its role while revealing a second reabsorptive pathway.

    Evidence Xenopus oocyte and brush-border vesicle transport assays, immunohistochemistry, and Urat1 knockout mouse urinary phenotyping

    PMID:20544513 PMID:21074513 PMID:21148271

    Open questions at the time
    • Identity of the residual urate reabsorptive transporter unknown
    • Endogenous counter-substrate driving exchange in vivo not defined
  5. 2010 High

    Demonstrating salicylate as both a transported substrate and a dose-dependent modulator explained the long-standing paradox of biphasic salicylate effects on urate excretion.

    Evidence Radiolabeled transport and trans-stimulation assays in HEK293-URAT1 and Xenopus oocytes

    PMID:20560471

    Open questions at the time
    • Structural basis of dual substrate/inhibitor behavior not resolved at this stage
  6. 2013 Medium

    Showing that disease mutants are retained in the ER established protein misfolding/mistrafficking as a mechanism of loss-of-function, beyond simple loss of intrinsic transport.

    Evidence Urate uptake assays plus immunofluorescence colocalization with ER markers for p.G366R, p.L415_G417del, p.T467M

    PMID:23386035

    Open questions at the time
    • Whether folding can be pharmacologically rescued untested
    • Generality across all hypouricemia variants unknown
  7. 2013 Medium

    Detecting URAT1 on ependymal cilia broadened its role beyond kidney to potential CSF urate regulation.

    Evidence KO-validated immunohistochemistry of mouse brain ventricular surfaces

    PMID:24156345

    Open questions at the time
    • Functional transport at ependyma not directly measured
    • Physiological consequence for CSF urate unestablished
  8. 2016 Medium

    Ancestral resurrection showed URAT1 urate affinity rose during primate evolution, framing high urate reabsorption as a derived primate trait.

    Evidence Ancestral sequence reconstruction and transport assays comparing resurrected and extant orthologs

    PMID:27352852

    Open questions at the time
    • Selective advantage driving affinity increase inferred, not demonstrated
    • Specific residues only partially mapped
  9. 2020 Medium

    Extending the substrate repertoire to xanthine and showing GLUT9 cooperativity, plus population-scale rare-variant analysis, connected URAT1 transport directly to heritable serum urate variation.

    Evidence Oocyte/MDCKII transcellular xanthine assays and functional assays on rare variants from whole-genome sequencing with variance component analysis

    PMID:32005656 PMID:33132325

    Open questions at the time
    • Physiological importance of xanthine transport relative to urate unclear
    • Functional effect of many rare variants still uncharacterized
  10. 2025 High

    Cryo-EM in multiple conformational states and identification of AKT/SGK1 phosphorylation at Thr408 together provided the structural transport cycle and a signaling mechanism linking hyperinsulinemia and salt to elevated urate.

    Evidence Cryo-EM with mutagenesis and transport assays; kinase screening, phospho-site mutagenesis (Arg405, Thr408), and human cohort validation

    PMID:40100301 PMID:40169562

    Open questions at the time
    • Phosphatase counter-regulating Thr408 not identified
    • Structures of phosphorylated state not resolved
    • Integration of PDZK1 scaffolding into structural model incomplete

Open questions

Synthesis pass · forward-looking unresolved questions
  • How URAT1 contributes mechanistically to extrarenal tissues (cardiomyocyte injury, hepatic steatosis, BAT thermogenesis, redox homeostasis) and how its surface abundance is dynamically controlled remain incompletely defined.
  • Direct transport function in liver/BAT not measured in situ
  • Causal chain from URAT1 activity to MAPK/NLRP3/UCP1 outcomes unresolved
  • Mechanisms of post-translational protein-level regulation in obesity not defined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 6 GO:0140104 molecular carrier activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1 GO:0005929 cilium 1
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-1430728 Metabolism 2
Partners
GLUT9PDZK1

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2025 Cryo-EM structures of native hURAT1 bound with anti-gout drugs (dotinurad, benzbromarone, lesinurad, verinurad) in the inward-open state, and with urate in inward-open, outward-open, and occluded states were solved. Complemented by mutagenesis and cell-based assays, these structures reveal the mechanisms of urate reabsorption and hURAT1 inhibition, providing a structural framework for understanding the transport cycle and drug binding. Cryo-electron microscopy, site-directed mutagenesis, cell-based transport assays Cell discovery High 40169562
2004 PDZK1 interacts with URAT1 via the PDZ motif at the extreme C-terminal intracellular region of URAT1 and the first, second, and fourth PDZ domains of PDZK1. This interaction enhances urate transport activity (1.4-fold increase in Vmax) and increases surface expression of URAT1 at the apical membrane of renal proximal tubular cells. Yeast two-hybrid screen, in vitro binding assay, surface plasmon resonance, co-immunoprecipitation, colocalization by microscopy, urate transport assays in HEK293 cells The Journal of biological chemistry High 15304510
2004 Loss-of-function mutations in SLC22A12 encoding URAT1 cause renal hypouricemia. URAT1 is the primary reabsorptive urate transporter at the apical membrane of renal proximal tubules and is the target of uricosuric drugs (benzbromarone, probenecid) and the anti-uricosuric drug pyrazinamide in vivo, as demonstrated by pyrazinamide failing to affect urate clearance in homozygous/compound heterozygous SLC22A12 mutant patients. SLC22A12 gene sequencing in 32 patients, pharmacological loading tests (probenecid, benzbromarone, pyrazinamide), urate clearance measurements Journal of the American Society of Nephrology : JASN High 14694169
2011 URAT1 expressed in MDCK cells localizes mainly to the apical membrane (as shown by GFP fusion imaging) and mediates time- and dose-dependent urate uptake with a Km of 570.7 µmol/L. Multiple uricosuric drugs (benzbromarone and metabolites, probenecid, indomethacin, salicylate, E3040) inhibit URAT1-mediated urate uptake dose-dependently with IC50 values ranging from 0.05–716 µmol/L. Stable expression in MDCK cells, urate uptake assays, GFP fusion protein localization by microscopy, pharmacological inhibition studies Nephrology (Carlton, Vic.) High 21272127
2010 URAT1 (rUrat1) in rats is localized at the apical membrane of proximal tubular epithelial cells and mediates chloride-susceptible urate transport (Km 1773 µM), inhibited by benzbromarone and trans-stimulated by lactate and pyrazinecarboxylic acid (PZA), consistent with a role in renal urate reabsorption. Gene expression in Xenopus oocytes, brush-border membrane vesicle (BBMV) transport assays, immunohistochemistry in rat kidney Biochimica et biophysica acta High 21074513
2010 SLC22A12 (Urat1) knockout mice show significantly higher urinary urate/creatinine ratios than wild-type mice, confirming attenuated renal urate reabsorption via Urat1. However, residual urate reabsorption remains, indicating at least one other urate reabsorptive transporter exists in the mouse kidney. Gene targeting (exons 1–4 replaced by pMC1neo-polyA), urinary urate/creatinine measurement, plasma urate measurement Nucleosides, nucleotides & nucleic acids High 20544513
2010 URAT1 missense mutations R406C and G444R found in Iraqi Jewish patients dramatically impair urate uptake into Xenopus oocytes. Additionally, URAT1 facilitates urate efflux (secretion), which was also abolished in the mutants, indicating URAT1 mediates bidirectional urate transport. Xenopus laevis oocyte transport assays (uptake and efflux) with wild-type and mutant URAT1 Nephrology, dialysis, transplantation High 21148271
2010 Salicylate is a transport substrate of URAT1 (Km 25.3 µM in oocytes) and also a cis-inhibitor of urate uptake (IC50 23.9 µM in HEK293-URAT1 cells). Salicylate injected into URAT1-expressing oocytes stimulates urate uptake (trans-stimulation), explaining the paradoxical dose-dependent effect of salicylate on renal urate excretion: at low doses, salicylate acts as an exchange substrate facilitating urate reabsorption; at high doses, it competitively inhibits URAT1. Radiolabeled transport assays in HEK293-URAT1 cells and Xenopus oocytes, trans-stimulation experiments Nihon Jinzo Gakkai shi High 20560471
2007 Morin competitively inhibits hURAT1-mediated urate uptake in HEK293 cells with IC50 of 2.0 µM and Ki of 5.74 µM. hURAT1 protein is sorted to the apical membrane of transfected cells as confirmed by confocal microscopy. Transfection of HEK293 cells with hURAT1, radiolabeled urate uptake assays, confocal microscopy of GFP-tagged transporter, kinetic analysis Drug metabolism and disposition Medium 17325024
2016 Ancestral URAT1 proteins were computationally inferred, resurrected, and functionally assayed, revealing that URAT1 affinity for uric acid increased during primate evolution, driven by a few amino acid replacements. Human and baboon URAT1 proteins have higher affinity for uric acid than rat and mouse orthologs. Ancestral sequence reconstruction, resurrection of ancient URAT1 proteins, in vitro transport assays comparing orthologs Molecular biology and evolution Medium 27352852
2004 Functional analysis in Xenopus oocytes showed that the SLC22A12 deletion mutation 313A (deletion of residues 313D-333P) has no urate transport activity, identifying it as a loss-of-function mutation causing renal hypouricemia. Xenopus oocyte expression system with urate transport assay Kidney international Medium 15327384
2013 URAT1 variants p.G366R, p.L415_G417del, and p.T467M show significantly decreased urate uptake in functional studies and are mislocalized (accumulate in the endoplasmic reticulum rather than the plasma membrane), suggesting loss-of-function via protein misfolding. Urate uptake assays, immunofluorescence colocalization with ER markers in transfected cells European journal of human genetics : EJHG Medium 23386035
2013 URAT1 is expressed on the cilia and apical surface of ventricular ependymal cells lining the lateral ventricle, dorsal/ventral third ventricle, aqueduct, and fourth ventricle in the mouse brain, suggesting a role in regulating urate levels in cerebrospinal fluid. Immunohistochemistry of wild-type and URAT1 knockout mouse brain; specificity confirmed by absence of staining in knockout Fluids and barriers of the CNS Medium 24156345
2004 The hURAT1 gene promoter was cloned and the transcription initiation site mapped 337 bp upstream of the ATG start codon. The minimal functional promoter is within 253 bp. Testosterone significantly increases promoter activity, suggesting hormonal regulation underlies sex-related differences in urate levels. Primer extension, 5'-RACE, promoter-luciferase reporter constructs transfected in OK cells, testosterone stimulation Biochimica et biophysica acta Medium 15566944
2018 Genetic and pharmacological inhibition of SGLT2 enhanced fractional renal urate excretion in mice. URAT1 knockout mice demonstrated that URAT1 is required for the acute uricosuric effect of the SGLT2 inhibitor canagliflozin, placing URAT1 downstream in the luminal glucose-mediated uricosuric mechanism. Gene-targeted mouse models (Urat1-KO, Sglt2-KO, Sglt1-KO, Glut9 tubular KO), SGLT2 inhibitor treatment, renal clearance studies American journal of physiology. Renal physiology Medium 30427222
2021 URAT1 is expressed in the liver and brown adipose tissue (BAT) in addition to the kidney. In high-fat diet mice, URAT1 expression increased in BAT. Pharmacological inhibition with dotinurad (a URAT1-selective inhibitor) attenuated hepatic steatosis and BAT whitening via UCP1 activation, ameliorating insulin resistance. Western blot for URAT1 expression in liver and BAT, dotinurad treatment of HFD mice, metabolic phenotyping Molecular metabolism Medium 34863940
2023 URAT1 is expressed in cardiomyocytes and functions as a uric acid transporter in this cell type. Palmitic acid increases URAT1 expression in neonatal rat cardiomyocytes and induces apoptosis, oxidative stress, and inflammatory responses via the MAPK pathway; URAT1-selective inhibition with dotinurad attenuates these effects. Western blot and functional transport assay in cardiomyocytes, palmitic acid stimulation, dotinurad treatment, HFD mouse model iScience Medium 37694143
2025 URAT1 cell-surface abundance and urate transport activity are regulated by phosphorylation of URAT1 at Thr408, stimulated by hyperinsulinemia via AKT kinase. SGK1, induced by high salt, also phosphorylates URAT1-Thr408 via the same pathway, increasing URAT1 activity. Arg405 is essential for these kinases to phosphorylate URAT1-Thr408. Kinase screening, single-cell data analysis, cell culture experiments with AKT/SGK1 inhibition and activation, URAT1 mutagenesis (Arg405, Thr408), urate transport assays in transfected cells The Journal of clinical investigation High 40100301
2020 Xanthine (but not hypoxanthine) is a substrate of URAT1, as demonstrated by uptake assays in URAT1-expressing Xenopus oocytes. Transcellular transport of xanthine in MDCKII cells co-expressing URAT1 and GLUT9 was significantly higher than in cells expressing either transporter alone or mock cells, indicating cooperative reabsorption. Radiolabeled xanthine/hypoxanthine uptake assays in Xenopus oocytes expressing URAT1 or GLUT9; transcellular transport in MDCKII cells; in vivo renal clearance in rats with dotinurad Biological & pharmaceutical bulletin Medium 33132325
2021 Loss of Urat1/Rst in knockout mice leads to disrupted redox homeostasis, with accumulation of metabolites related to pyrimidine, fatty acid, and amino acid metabolism distinct from Oat1 and Oat3 knockouts. Systems metabolic analysis revealed compensatory processes related to reactive oxygen species handling via Vitamin C metabolism and cofactor charging reactions. Metabolomics of Urat1 knockout mice, transcriptomics, genome-scale metabolic modeling (GEM), chemoinformatics Antioxidants (Basel, Switzerland) Medium 36979028
2021 In Urat1-Uox double knockout mice, exercise-induced AKI is associated with increased NLRP3 inflammasome activity (elevated IL-1β) and downregulation of Na+-K+-ATPase in the kidney. Xanthine oxidoreductase inhibitors (topiroxostat and allopurinol) improved renal injury and prevented EIAKI in these mice. Double KO mice (Urat1-Uox), forced swimming exercise test, Western blot for NLRP3, Na+-K+-ATPase, IL-1β; XOI treatment Journal of the American Society of Nephrology : JASN Medium 34799437
2017 ALPK1 overexpression in transgenic mice decreased renal URAT1 protein levels, and MSU crystals inhibited URAT1 expression through upregulation of ALPK1 in human kidney-2 cells, establishing ALPK1 as a negative regulator of URAT1 protein expression. ALPK1 transgenic mice (URAT1 protein by Western blot), ALPK1 siRNA knockdown in HK-2 cells with MSU crystal stimulation Rheumatology (Oxford, England) Low 28039413
2011 In leptin-deficient (ob/ob) and high-fat diet mice, URAT1 (Slc22a12) protein levels are increased in the kidney without significant changes in mRNA, suggesting post-translational regulation of URAT1 protein abundance in obesity. Western blot and RT-PCR of kidney tissue from ob/ob and high-fat diet mouse models Nucleosides, nucleotides & nucleic acids Low 22132989
2020 Long-chain unsaturated omega-3 fatty acids (eicosapentaenoic acid IC50 6.0 µM, α-linolenic acid IC50 14.2 µM, docosahexaenoic acid IC50 15.2 µM) inhibit URAT1-mediated urate transport more potently than saturated fatty acids, as determined in cells transiently expressing URAT1. In vitro transport assay using cells transiently expressing URAT1, IC50 determination for 25 fatty acids Nutrients Medium 32486008
2020 Rare SLC22A12 variants that reduce URAT1 urate transport activity account for >10% of heritability in serum urate levels (missing heritability), as demonstrated by functional transport assays on identified rare variants combined with population genetic analysis. Whole genome sequencing (ToMMo cohort), functional urate uptake assays on identified rare variants, variance component analysis Genetics Medium 32005656

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Clinical and molecular analysis of patients with renal hypouricemia in Japan-influence of URAT1 gene on urinary urate excretion. Journal of the American Society of Nephrology : JASN 297 14694169
2001 rst and its paralogue kirre act redundantly during embryonic muscle development in Drosophila. Development (Cambridge, England) 176 11684659
2004 The multivalent PDZ domain-containing protein PDZK1 regulates transport activity of renal urate-anion exchanger URAT1 via its C terminus. The Journal of biological chemistry 152 15304510
2018 SGLT2 inhibition and renal urate excretion: role of luminal glucose, GLUT9, and URAT1. American journal of physiology. Renal physiology 140 30427222
1995 Restricted expression of the irreC-rst protein is required for normal axonal projections of columnar visual neurons. Neuron 110 7646884
2015 Depletion of Uric Acid Due to SLC22A12 (URAT1) Loss-of-Function Mutation Causes Endothelial Dysfunction in Hypouricemia. Circulation journal : official journal of the Japanese Circulation Society 101 25739858
2004 A high prevalence of renal hypouricemia caused by inactive SLC22A12 in Japanese. Kidney international 95 15327384
2010 The RST and PARP-like domain containing SRO protein family: analysis of protein structure, function and conservation in land plants. BMC genomics 85 20226034
2011 Interactions of urate transporter URAT1 in human kidney with uricosuric drugs. Nephrology (Carlton, Vic.) 84 21272127
2008 Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese. Clinical genetics 79 18492088
1996 Reorganization of membrane contacts prior to apoptosis in the Drosophila retina: the role of the IrreC-rst protein. Development (Cambridge, England) 78 8674431
2002 Differential expression and induction of two Drosophila cytochrome P450 genes near the Rst(2)DDT locus. Insect molecular biology 77 12144699
2021 Apigenin ameliorates hyperuricemic nephropathy by inhibiting URAT1 and GLUT9 and relieving renal fibrosis via the Wnt/β-catenin pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 72 34044255
2004 The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia. Pediatric nephrology (Berlin, Germany) 68 15054642
2016 Coevolution of URAT1 and Uricase during Primate Evolution: Implications for Serum Urate Homeostasis and Gout. Molecular biology and evolution 67 27352852
2006 Molecular analysis of the SLC22A12 (URAT1) gene in patients with primary gout. Rheumatology (Oxford, England) 63 16837472
2005 Analyses of coding region polymorphisms in apical and basolateral human organic anion transporter (OAT) genes [OAT1 (NKT), OAT2, OAT3, OAT4, URAT (RST)]. Kidney international 61 16164626
2000 [D-Leu1]Microcystin-LR, from the cyanobacterium Microcystis RST 9501 and from a Microcystis bloom in the Patos Lagoon estuary, Brazil. Phytochemistry 59 11140597
2006 Association between intronic SNP in urate-anion exchanger gene, SLC22A12, and serum uric acid levels in Japanese. Life sciences 57 16920156
2021 URAT1-selective inhibition ameliorates insulin resistance by attenuating diet-induced hepatic steatosis and brown adipose tissue whitening in mice. Molecular metabolism 52 34863940
2019 Novel urate transporter 1 (URAT1) inhibitors: a review of recent patent literature (2016-2019). Expert opinion on therapeutic patents 52 31593642
2011 Clinical and functional characterization of URAT1 variants. PloS one 51 22194875
2010 URAT1 mutations cause renal hypouricemia type 1 in Iraqi Jews. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 50 21148271
2005 IrreC/rst-mediated cell sorting during Drosophila pupal eye development depends on proper localisation of DE-cadherin. Development (Cambridge, England) 49 15788453
2013 Novel allelic variants and evidence for a prevalent mutation in URAT1 causing renal hypouricemia: biochemical, genetics and functional analysis. European journal of human genetics : EJHG 47 23386035
2002 Galectin 9 is the sugar-regulated urate transporter/channel UAT. Glycoconjugate journal 47 14758072
2021 A brief review of urate transporter 1 (URAT1) inhibitors for the treatment of hyperuricemia and gout: Current therapeutic options and potential applications. European journal of pharmacology 46 34216576
2018 Research on the pharmacodynamics and mechanism of Fraxini Cortex on hyperuricemia based on the regulation of URAT1 and GLUT9. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 44 29990831
2015 Functional analysis of novel allelic variants in URAT1 and GLUT9 causing renal hypouricemia type 1 and 2. Clinical and experimental nephrology 44 26500098
2014 Effects of Xie-Zhuo-Chu-Bi-Fang on miR-34a and URAT1 and their relationship in hyperuricemic mice. Journal of ethnopharmacology 44 25535087
2021 Fucoidan from Laminaria japonica Inhibits Expression of GLUT9 and URAT1 via PI3K/Akt, JNK and NF-κB Pathways in Uric Acid-Exposed HK-2 Cells. Marine drugs 42 33922488
2018 URAT1 and GLUT9 mutations in Spanish patients with renal hypouricemia. Clinica chimica acta; international journal of clinical chemistry 42 29486147
2016 The effects of URAT1/SLC22A12 nonfunctional variants, R90H and W258X, on serum uric acid levels and gout/hyperuricemia progression. Scientific reports 42 26821810
2016 Prevalence of URAT1 allelic variants in the Roma population. Nucleosides, nucleotides & nucleic acids 39 27906637
2014 Pallidifloside D, a saponin glycoside constituent from Smilax riparia, resist to hyperuricemia based on URAT1 and GLUT9 in hyperuricemic mice. Journal of ethnopharmacology 38 25267580
2020 Uric Acid Has Direct Proinflammatory Effects on Human Macrophages by Increasing Proinflammatory Mediators and Bacterial Phagocytosis Probably via URAT1. Biomolecules 36 32283759
2014 Complex analysis of urate transporters SLC2A9, SLC22A12 and functional characterization of non-synonymous allelic variants of GLUT9 in the Czech population: no evidence of effect on hyperuricemia and gout. PloS one 36 25268603
2015 High frequency of SLC22A12 variants causing renal hypouricemia 1 in the Czech and Slovak Roma population; simple and rapid detection method by allele-specific polymerase chain reaction. Urolithiasis 32 26033041
2015 Discovery of URAT1 SNPs and association between serum uric acid levels and URAT1. BMJ open 32 26603249
2010 Identification and functional characterization of uric acid transporter Urat1 (Slc22a12) in rats. Biochimica et biophysica acta 30 21074513
2020 Omega-3 Polyunsaturated Fatty Acids Inhibit the Function of Human URAT1, a Renal Urate Re-Absorber. Nutrients 29 32486008
2020 Hypouricemic Effects of Extracts from Urtica hyperborea Jacq. ex Wedd. in Hyperuricemia Mice through XOD, URAT1, and OAT1. BioMed research international 28 32083126
2009 Multiple single nucleotide polymorphisms in the human urate transporter 1 (hURAT1) gene are associated with hyperuricaemia in Han Chinese. Journal of medical genetics 28 19833602
2006 Structural and functional characterization of a recombinant sticholysin I (rSt I) from the sea anemone Stichodactyla helianthus. Toxicon : official journal of the International Society on Toxinology 28 17067649
2005 Recurrent URAT1 gene mutations and prevalence of renal hypouricemia in Japanese. Pediatric nephrology (Berlin, Germany) 28 15772829
2004 Molecular cloning and characterization of a human urate transporter (hURAT1) gene promoter. Biochimica et biophysica acta 28 15566944
2012 Urate transporter gene SLC22A12 polymorphisms associated with obesity and metabolic syndrome in Caucasians with hypertension. Kidney & blood pressure research 27 22688828
2010 Establishment and analysis of SLC22A12 (URAT1) knockout mouse. Nucleosides, nucleotides & nucleic acids 27 20544513
2007 Morin (3,5,7,2',4'-pentahydroxyflavone) exhibits potent inhibitory actions on urate transport by the human urate anion transporter (hURAT1) expressed in human embryonic kidney cells. Drug metabolism and disposition: the biological fate of chemicals 27 17325024
2011 The increased protein level of URAT1 was observed in obesity/metabolic syndrome model mice. Nucleosides, nucleotides & nucleic acids 26 22132989
2018 Validation of Version 3.0 of the Breast Cancer Genetics Referral Screening Tool (B-RST™). Genetics in medicine : official journal of the American College of Medical Genetics 25 29740170
2008 Prevalence of hypouricaemia and SLC22A12 mutations in healthy Korean subjects. Nephrology (Carlton, Vic.) 25 19019168
2024 Piperine Improves Hyperuricemic Nephropathy by Inhibiting URAT1/GLUT9 and the AKT-mTOR Pathway. Journal of agricultural and food chemistry 23 38498316
2000 A screen for dominant modifiers of the irreC-rst cell death phenotype in the developing Drosophila retina. Genetics 23 10978286
2023 Pharmacological evaluation of a novel skeleton compound isobavachin (4',7-dihydroxy-8-prenylflavanone) as a hypouricemic agent: Dual actions of URAT1/GLUT9 and xanthine oxidase inhibitory activity. Bioorganic chemistry 22 36753966
2020 Contribution of Rare Variants of the SLC22A12 Gene to the Missing Heritability of Serum Urate Levels. Genetics 22 32005656
2012 Novel URAT1 mutations caused acute renal failure after exercise in two Chinese families with renal hypouricemia. Gene 22 23043931
2008 T6092C polymorphism of SLC22A12 gene is associated with serum uric acid concentrations in Korean male subjects. Clinica chimica acta; international journal of clinical chemistry 22 18824160
2006 Analysis of mutations in the urate transporter 1 (URAT1) gene of Japanese patients with hypouricemia in northern Japan and review of the literature. Renal failure 22 16703794
2021 Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1-Uox Double Knockout Mice. Journal of the American Society of Nephrology : JASN 21 34799437
2016 Urat1-Uox double knockout mice are experimental animal models of renal hypouricemia and exercise-induced acute kidney injury. Nucleosides, nucleotides & nucleic acids 21 27906636
2013 Ependymal cells of the mouse brain express urate transporter 1 (URAT1). Fluids and barriers of the CNS 21 24156345
2023 Hyperuricemia exacerbates abdominal aortic aneurysm formation through the URAT1/ERK/MMP-9 signaling pathway. BMC cardiovascular disorders 20 36710339
2017 Negative correlation between serum uric acid and kidney URAT1 mRNA expression caused by resveratrol in rats. Molecular nutrition & food research 20 28499081
2005 The adaptor protein X11Lalpha/Dmint1 interacts with the PDZ-binding domain of the cell recognition protein Rst in Drosophila. Developmental biology 20 16380111
2016 (E)-2-(4-bromophenyl)-1-(2, 4-dihydroxyphenyl)ethanone oxime is a potential therapeutic agent for treatment of hyperuricemia through its dual inhibitory effects on XOD and URAT1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 27951420
2020 Renal Reabsorptive Transport of Uric Acid Precursor Xanthine by URAT1 and GLUT9. Biological & pharmaceutical bulletin 17 33132325
2019 Urate Transporter URAT1 in Hyperuricemia: New Insights from Hyperuricemic Models. Annals of clinical and laboratory science 17 31882426
2012 Two surfaces of a conserved interdomain linker differentially affect output from the RST sensing module of the Bacillus subtilis stressosome. Journal of bacteriology 17 22609918
2024 Protecting against ferroptosis in hyperuricemic nephropathy: The potential of ferrostatin-1 and its inhibitory effect on URAT1. European journal of pharmacology 16 38556118
2022 Identification of Inhibitory Activities of Dietary Flavonoids against URAT1, a Renal Urate Re-Absorber: In Vitro Screening and Fractional Approach Focused on Rooibos Leaves. Nutrients 16 35276934
2018 Renal hypouricemia caused by novel compound heterozygous mutations in the SLC22A12 gene: a case report with literature review. BMC medical genetics 16 30097038
2017 URAT1 inhibition by ALPK1 is associated with uric acid homeostasis. Rheumatology (Oxford, England) 16 28039413
2022 The Active Components of Sunflower (Helianthus annuus L.) Calathide and the Effects on Urate Nephropathy Based on COX-2/PGE2 Signaling Pathway and the Urate Transporter URAT1, ABCG2, and GLUT9. Frontiers in nutrition 15 35083262
2016 Additive composite ABCG2, SLC2A9 and SLC22A12 scores of high-risk alleles with alcohol use modulate gout risk. Journal of human genetics 15 27225847
2016 Immunohistochemical and in situ hybridization study of urate transporters GLUT9/URATv1, ABCG2, and URAT1 in the murine brain. Fluids and barriers of the CNS 15 27955673
2009 High-resolution melting analysis for the rapid detection of an intronic single nucleotide polymorphism in SLC22A12 in male patients with primary gout in China. Scandinavian journal of rheumatology 15 19306160
2007 Absence of SLC22A12 gene mutations in Greek Caucasian patients with primary renal hypouricaemia. Scandinavian journal of clinical and laboratory investigation 15 17891652
2003 A study of Y-chromosome microsatellite variation in sub-Saharan Africa: a comparison between F(ST) and R(ST) genetic distances. Human biology 15 14527196
2021 Substantial anti-gout effect conferred by common and rare dysfunctional variants of URAT1/SLC22A12. Rheumatology (Oxford, England) 14 33821957
2021 Novel natural scaffold as hURAT1 inhibitor identified by 3D-shape-based, docking-based virtual screening approach and biological evaluation. Bioorganic chemistry 14 34775203
2010 [Human renal urate transpoter URAT1 mediates the transport of salicylate]. Nihon Jinzo Gakkai shi 14 20560471
2023 Ethanolic Extract from Limonia acidissima L. Fruit Attenuates Serum Uric Acid Level via URAT1 in Potassium Oxonate-Induced Hyperuricemic Rats. Pharmaceuticals (Basel, Switzerland) 13 36986518
2015 Characteristics of Recombinant Phytase (rSt-Phy) of the Thermophilic mold Sporotrichum thermophile and its applicability in dephytinizing foods. Applied biochemistry and biotechnology 13 26433599
2010 The effects of acute dynamic exercise on haemostasis in fi rst class Scottish football referees. British journal of sports medicine 13 19019900
2024 Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia. Bioorganic chemistry 12 38669781
2018 Zurampic Protects Pancreatic β-Cells from High Uric Acid Induced-Damage by Inhibiting URAT1 and Inactivating the ROS/AMPK/ERK Pathways. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 12 29843128
2011 rst transcriptional activity influences kirre mRNA concentration in the Drosophila pupal retina during the final steps of ommatidial patterning. PloS one 12 21857931
2025 Molecular mechanisms of urate transport by the native human URAT1 and its inhibition by anti-gout drugs. Cell discovery 11 40169562
2023 URAT1 is expressed in cardiomyocytes and dotinurad attenuates the development of diet-induced metabolic heart disease. iScience 11 37694143
2022 Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene. Rheumatology (Oxford, England) 11 34255816
2019 Polymorphisms of ABCG2 and SLC22A12 Genes Associated with Gout Risk in Vietnamese Population. Medicina (Kaunas, Lithuania) 11 30621105
2024 Salinomycin, a potent inhibitor of XOD and URAT1, ameliorates hyperuricemic nephropathy by activating NRF2, modulating the gut microbiota, and promoting SCFA production. Chemico-biological interactions 10 39222901
2023 Loss of the Kidney Urate Transporter, Urat1, Leads to Disrupted Redox Homeostasis in Mice. Antioxidants (Basel, Switzerland) 10 36979028
2013 [Effect of total saponin of Dioscorea on chronic hyperuricemia and expression of URAT1 in rats]. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica 10 24199570
2003 Interspecies comparison of a gene pair with partially redundant function: the rst and kirre genes in D. virilis and D. melanogaster. Journal of molecular evolution 10 12574866
2025 Gene-environment interaction modifies the association between hyperinsulinemia and serum urate levels through SLC22A12. The Journal of clinical investigation 9 40100301
2022 Genetic Association Between SLC22A12 Variants and Susceptibility to Hyperuricemia: A Meta-Analysis. Genetic testing and molecular biomarkers 9 35225677
2022 Design, synthesis, and biological studies of dual URAT1 inhibitor and FXR agonist based on benzbromarone. Bioorganic & medicinal chemistry 9 36347120
2019 Amplicon targeted resequencing for SLC2A9 and SLC22A12 identified novel mutations in hypouricemia subjects. Molecular genetics & genomic medicine 9 31131560

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