ArticleBritish journal of pharmacology2010
Functional characterization of nonsynonymous single nucleotide polymorphisms in the human organic anion transporter 4 (hOAT4).
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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18 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Genome wide association study of uric acid in Indian population and interaction of identified variants with Type 2 diabetes.Scientific reports · 2016Pooled it
- Examining the Association of Rare Allelic Variants in Urate TransportersDisease markers · 2024Article
- Function of Uric Acid Transporters and Their Inhibitors in Hyperuricaemia.Frontiers in pharmacology · 2021Article
- Structural Insights into the Atomistic Mechanisms of Uric Acid Recognition and Translocation of Human Urate Anion Transporter 1.ACS omega · 2020Article
- Multifaceted genome-wide study identifies novel regulatory loci in SLC22A11 and ZNF45 for body mass index in Indians.Molecular genetics and genomics : MGG · 2020Article
- The role of solute carrier (SLC) transporters in actinomycin D pharmacokinetics in paediatric cancer patients.European journal of clinical pharmacology · 2018Article
- Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition.Journal of personalized medicine · 2018Review
- Renal Drug Transporters and Drug Interactions.Clinical pharmacokinetics · 2017Review
- Trafficking and other regulatory mechanisms for organic anion transporting polypeptides and organic anion transporters that modulate cellular drug and xenobiotic influx and that are dysregulated in disease.British journal of pharmacology · 2017Review
- Urate Handling in the Human Body.Current rheumatology reports · 2016Review
- Human oligopeptide transporter 2 (PEPT2) mediates cellular uptake of polymyxins.The Journal of antimicrobial chemotherapy · 2016Article
- Human organic anion transporting polypeptide 1A2 (OATP1A2) mediates cellular uptake of all-trans-retinol in human retinal pigmented epithelial cells.British journal of pharmacology · 2015Article
- The altered renal and hepatic expression of solute carrier transporters (SLCs) in type 1 diabetic mice.PloS one · 2015Article
- Article
- Functional analysis of novel polymorphisms in the human SLCO1A2 gene that encodes the transporter OATP1A2.The AAPS journal · 2013Article
- Renal organic anion transporters (SLC22 family): expression, regulation, roles in toxicity, and impact on injury and disease.The AAPS journal · 2013Review
- OATPs, OATs and OCTs: the organic anion and cation transporters of the SLCO and SLC22A gene superfamilies.British journal of pharmacology · 2012Review
- Genetic variants of human organic anion transporter 4 demonstrate altered transport of endogenous substrates.American journal of physiology. Renal physiology · 2010Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeThe human organic anion transporter (hOAT) family of transmembrane carrier proteins mediate the cellular flux of anionic substances, including certain hormones and anti-cancer drugs. hOAT4 is highly expressed at the apical membrane of the renal tubular cell and facilitates drug re-absorption in the kidney. In the present study, the impact of 10 nonsynonymous single nucleotide polymorphisms (SNPs) of hOAT4 on transport function in COS-7 cells was characterized. EXPERIMENTAL APPROACH: Transport uptake assay was used to assess the function of the variant transporters. Cell surface biotinylation and western blot analysis were used to investigate the expression characteristics of the transporter proteins. Comparative modelling was used to interpret the influence of nonsynonymous changes in terms of hOAT4 structure. KEY
resultsFour naturally occurring hOAT4 variants (L29P, R48Y, V155G and T392I) exhibited a significant loss of function. Substitution of leucine-29, which is a conserved residue in OATs, with a proline residue, impaired the synthesis or the apparent stability of the transporter and membrane insertion was disrupted in the R48Y variant. In the case of the V155G and T392I variants, impaired function was due to decreased affinity of the transporter for oestrone sulphate and impaired transporter-substrate turnover respectively. The T392I variant was inhibited more extensively than the wild-type transporter by the cationic substrate tetraethyl ammonium. CONCLUSIONS AND IMPLICATIONS: Several naturally occurring SNPs encode variant hOAT4s that may impair the renal tubular re-absorption of important drug substrates.
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