ArticleThe Journal of biological chemistry2010
Human sodium phosphate transporter 4 (hNPT4/SLC17A3) as a common renal secretory pathway for drugs and urate.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 2 of them syntheses that pooled it.
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Who cites it
65 citing papers in PubMed, 2 syntheses or guidelines pooled it, 156 citations in OpenAlex.
- Trans-ancestry GWAS identifies 59 loci and improves risk prediction and fine-mapping for kidney stone disease.Nature communications · 2025Pooled it
- Genome-wide meta-analysis of iron status biomarkers and the effect of iron on all-cause mortality in HUNT.Communications biology · 2022Pooled it
- Genetic factors associated with elevation of uric acid after treatment with thiazide-like diuretic in patients with essential hypertension.Hypertension research : official journal of the Japanese Society of Hypertension · 2020Trial
- Evolutionary history of disease-susceptibility loci identified in longitudinal exome-wide association studies.Molecular genetics & genomic medicine · 2019Trial
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- ABCG2 transporter: Structural and functional associations with gout (Review).International journal of molecular medicine · 2026Review
- Role of urate transporters in the kidneys and intestine in uric acid homeostasis.Kidney research and clinical practice · 2026Article
- Rare variant optimized GWAS with functional validation identifies causal architecture of kidney function in East Asian population.Scientific reports · 2026Article
- Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse Model.Diseases (Basel, Switzerland) · 2025Article
- Genome-wide association studies and traditional Chinese medicine in hyperuricemia: current evidence and mechanistic insights.Frontiers in pharmacology · 2025Review
- Loop diuretics inhibit kynurenic acid production and kynurenine aminotransferases activity in rat kidneys.Pharmacological reports : PR · 2024Article
- SLC17A1/3 transporters mediate renal excretion of Lac-Phe in mice and humans.Nature communications · 2024Article
- Identification of three distinct cell populations for urate excretion in human kidneys.The journal of physiological sciences : JPS · 2024Article
- The impact of solute carrier proteins on disrupting substance regulation in metabolic disorders: insights and clinical applications.Frontiers in pharmacology · 2024Review
- Population pharmacokinetics, pharmacodynamics and pharmacogenetics modelling of oxypurinol in Hmong adults with gout and/or hyperuricemia.British journal of clinical pharmacology · 2023Article
- Linkage analysis using whole exome sequencing data implicates SLC17A1, SLC17A3, TATDN2 and TMEM131L in type 1 diabetes in Kuwaiti families.Scientific reports · 2023Article
- Dysuricemia-A New Concept Encompassing Hyperuricemia and Hypouricemia.Biomedicines · 2023Review
- Purine Metabolism Dysfunctions: Experimental Methods of Detection and Diagnostic Potential.International journal of molecular sciences · 2023Review
- Implications of tRNA abundance on translation elongation across bovine tissues.Frontiers in genetics · 2023Article
- Differences of Uric Acid Transporters Carrying Extracellular Vesicles in the Urine from Uric Acid and Calcium Stone Formers and Non-Stone Formers.International journal of molecular sciences · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The evolutionary loss of hepatic urate oxidase (uricase) has resulted in humans with elevated serum uric acid (urate). Uricase loss may have been beneficial to early primate survival. However, an elevated serum urate has predisposed man to hyperuricemia, a metabolic disturbance leading to gout, hypertension, and various cardiovascular diseases. Human serum urate levels are largely determined by urate reabsorption and secretion in the kidney. Renal urate reabsorption is controlled via two proximal tubular urate transporters: apical URAT1 (SLC22A12) and basolateral URATv1/GLUT9 (SLC2A9). In contrast, the molecular mechanism(s) for renal urate secretion remain unknown. In this report, we demonstrate that an orphan transporter hNPT4 (human sodium phosphate transporter 4; SLC17A3) was a multispecific organic anion efflux transporter expressed in the kidneys and liver. hNPT4 was localized at the apical side of renal tubules and functioned as a voltage-driven urate transporter. Furthermore, loop diuretics, such as furosemide and bumetanide, substantially interacted with hNPT4. Thus, this protein is likely to act as a common secretion route for both drugs and may play an important role in diuretics-induced hyperuricemia. The in vivo role of hNPT4 was suggested by two hyperuricemia patients with missense mutations in SLC17A3. These mutated versions of hNPT4 exhibited reduced urate efflux when they were expressed in Xenopus oocytes. Our findings will complete a model of urate secretion in the renal tubular cell, where intracellular urate taken up via OAT1 and/or OAT3 from the blood exits from the cell into the lumen via hNPT4.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.