Ask about this productRelated genes to: SLC22A12 antibody
- Gene:
- SLC22A12 NIH gene
- Name:
- solute carrier family 22 member 12
- Previous symbol:
- -
- Synonyms:
- OAT4L, RST, URAT1
- Chromosome:
- 11q13.1
- Locus Type:
- gene with protein product
- Date approved:
- 2002-07-31
- Date modifiied:
- 2016-02-18
Related products to: SLC22A12 antibody
Related articles to: SLC22A12 antibody
- Uric acid transporters mediate renal and extrarenal urate handling and may contribute to blood pressure (BP) regulation. This study examined the associations of common single-nucleotide polymorphisms (SNPs) in key urate transporter genes (SLC2A9, ABCG2, SLC17A3, SLC22A7, SLC22A6, SLC22A11, SLC22A12, and ABCC4) with salt sensitivity, longitudinal BP changes, and incident hypertension. Data were derived from the Baoji Salt-Sensitivity Study, a family-based cohort in which 514 Chinese adults completed a controlled dietary sodium intervention and were followed prospectively for 14 years. After multivariable adjustment and multiple-testing correction, ABCG2 rs2054576 and rs4491984 were associated with DBP response to low-salt diet; SLC22A6 rs4149170 with SBP and DBP responses; ABCG2 rs12505410 and SLC22A12 rs7932775 with DBP and MAP responses; and ABCC4 rs1189466 and rs17189390 with SBP, DBP, and MAP responses. During high-salt intake, SLC2A9 rs3733591 was associated with SBP and MAP responses; and SLC22A11 rs3759053, ABCC4 rs17189390 and rs9590211 were associated with SBP, DBP, and MAP responses. Over 14 years of follow-up, SLC2A9 rs3733591 and SLC17A3 rs1165165 were associated with longitudinal systolic BP (SBP) change; ABCG2 rs2054576, SLC22A7 rs2270860, SLC22A12 rs79226484, and ABCC4 rs1189466 were associated with diastolic BP (DBP) and MAP change; and SLC22A6 rs4149170 and ABCC4 rs9590220 and rs7322318 were associated with change in SBP, DBP and MAP. Additionally, ABCC4 rs7982809 and rs869951 were associated with incident hypertension over the 14-year follow-up. These findings suggest that genetic variation in urate transporters may contribute to salt sensitivity, long-term BP progression, and hypertension risk, supporting a possible role for urate-transport pathways in BP regulation. - Source: PubMed
Chang Ming-KeKong Ling-YunZhang Zhuo-RanYao ShiWang XinLi HaoWang YangGao Wei-Hua - Renal hypouricemia is caused by pathogenic variants in and . Current diagnostic thresholds based on serum uric acid (UA) (SUA < 2 mg/dl) and fractional excretion of UA (FEUA > 10%) may overlook individuals with monoallelic variants and mild hypouricemia, whose clinical implications remain incompletely defined. This study evaluated genotype-phenotype correlations across individuals with 0, 1, or 2 pathogenic alleles in a referral-based genetic testing cohort from Galicia (Western Europe). - Source: PubMed
Publication date: 2026/07/22
Carrera NoaUrisarri AdelaFortes-González PedroSánchez-Cazorla EloísaPiñeiro Yolanda GonzálezBarcia de la Iglesia AnaAmigo JorgeDíaz CándidoPedrosa PabloGarcía-Murias MaríaGonzález Miguel García - Hyperuricemia-induced gout is largely driven by impaired renal urate excretion, while current URAT1 inhibitors suffer from OAT1-mediated off-target toxicity. Our lead compound E1 potently inhibited URAT1 (IC50 = 3.02 μM) and reduced serum uric acid but exhibited OAT1 inhibition (IC50 = 4.78 μM) and HK-2 cytotoxicity (CC50 = 46.22 μM). To improve selectivity while retaining the core pharmacophore, a nitrogen-walk strategy was applied to design 48 azaindole derivatives. Pyrrolo[3,2-d]pyrimidine-based compound 17 was identified as the optimized candidate, exhibiting URAT1 inhibition (IC50 = 5.32 μM) with reduced OAT1 inhibition (IC50 = 30.11 μM), achieving a 6.7-fold selectivity improvement over E1. Compound 17 reduced serum uric acid by 77.7% at 2 mg/kg in an acute hyperuricemia mouse model and alleviated hepatic and renal injury in a chronic hyperuricemia model. It exhibited favorable druggability, including 87.9% oral bioavailability, a minimum effective dose below 0.5 mg/kg, and no observable toxicity up to 1000 mg/kg. - Source: PubMed
Jiang YuxinShi XiaoyuWu ZhenkunYang QianXu ShujingYu ZeqiYang MingyuWang MeiLiu ZhiyongMeng WeitingWu TingLiu XinyongPang JianxinYi FanZhan Peng - HP501, a novel highly selective renal urate transporter 1 (URAT1) inhibitor, represents a promising therapeutic option for hyperuricemia. This Phase I study evaluated the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of HP501 in Chinese gout patients. 37 patients with gout and hyperuricemia were enrolled in this single-center, open-label, dose-escalation study. Participants were sequentially assigned to receive HP501 at 60, 80, and 100 mg twice daily (BID) following single- and multiple-dose regimens. Safety assessments, PK parameters, and PD reductions were systematically evaluated. HP501 demonstrated an acceptable safety and tolerability profile across all dose cohorts. The most common adverse events (≥10% of patients) included gout flare (36.1%), prostatic hypertrophy (36.1%), elevated ALT (16.7%), and kidney stones (11.1%), all of which were mild to moderate in severity. PK analysis revealed dose-proportional increases in Cmax and AUC (60 to 100 mg BID), with corresponding dose-dependent reductions in serum UA levels. All patients achieved therapeutic UA targets (<360 µmol/L). These findings support the clinical advancement of HP501, with 60 to 100 mg BID identified as the recommended dose range for further investigation in subsequent trials. However, these findings are preliminary and limited by the single-center design, small sample size, and exclusion of female patients, warranting confirmation in larger, more diverse populations. - Source: PubMed
Chen LongxiaDing RuilinChen YuanweiLi XinghaiXiong TengqiongChen HongHu XiaojingZhou YiJiang FengPeng Qing - Impaired renal urate excretion is a major mechanism underlying hyperuricemia and gout, with urate transporter 1 (URAT1), encoded by SLC22A12, playing a central role in proximal tubular urate reabsorption. This review summarizes the biological relevance of URAT1, the pharmacological evolution of URAT1 inhibitors, and their clinical implications in urate-lowering therapy. Evidence from transporter biology, structural pharmacology, pharmacokinetic and pharmacodynamic studies, and clinical trials was narratively synthesized. URAT1 inhibitors lower serum urate by blocking renal tubular urate reabsorption and increasing urinary urate excretion, providing a mechanism complementary to xanthine oxidase inhibition. Early uricosuric agents established the clinical value of this approach but are limited by non-selective transporter inhibition, tolerability concerns, drug-drug interactions, and organ-specific safety issues. Newer selective URAT1 inhibitors have been developed to improve transporter selectivity, pharmacodynamic precision, and clinical usability. Current evidence supports selective URAT1 inhibition as an effective strategy for achieving serum urate targets, particularly in underexcretion-type hyperuricemia, while renal monitoring and prevention of uric acid stone formation remain important. Emerging agents may further expand treatment options, but long-term renal, hepatic, and cardiovascular safety require further validation. Overall, URAT1 inhibition represents a rational and increasingly precise therapeutic strategy for hyperuricemia and gout, with future research needed to define its long-term outcomes, comparative effectiveness, pharmacogenomic predictors, and broader cardio-renal-metabolic implications. - Source: PubMed
Publication date: 2026/08/17
Li GuangtaoWang YuZhang Zhuoli