Ask about this productRelated genes to: SLC22A3 antibody
- Gene:
- SLC22A3 NIH gene
- Name:
- solute carrier family 22 member 3
- Previous symbol:
- -
- Synonyms:
- OCT3, EMT
- Chromosome:
- 6q25.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-07-16
- Date modifiied:
- 2016-09-28
Related products to: SLC22A3 antibody
Related articles to: SLC22A3 antibody
- Human longevity arises from complex genetic and environmental interactions, yet the genetic basis of survival to extreme old age remains underexplored in Asian populations. We performed genome-wide association studies (GWAS) in a Taiwanese cohort, defining survival thresholds at ≥ 85, ≥ 90, and ≥ 95 years, and validated significant loci in an independent cohort. Multiple loci, including ZNF806, NUAK1, TANC1, SLC22A3, PTPRD, and PCSK2, were associated with longevity, of which 14 replicated with consistent effect directions (82% concordance). Allele frequencies aligned with East Asian references but diverged from prior Han Chinese studies, reflecting sub-ethnic variation. Polygenic risk scores (PRSs) alone showed limited predictive ability but provided statistically significant incremental improvement when integrated with clinical covariates. In the external validation cohort, adding PRS modestly improved model discrimination (AUC from 0.900 to 0.904 for ≥ 85 years and from 0.893 to 0.912 for ≥ 90 years) and yielded the largest improvement in the ≥ 95 group (AUC from 0.913 to 0.956; DeLong P < 10⁻⁸), with corresponding gains in reclassification metrics. These findings suggested that while clinical factors remained the primary predictors of survival, genetic risk captured by PRS contributed additional information, particularly at extreme longevity thresholds. Together, the results highlighted an age-dependent genetic architecture enriched for neural, cardio-metabolic, and stress-response pathways and supported the use of genetics-informed models as complementary tools for precision aging research in Taiwanese populations. - Source: PubMed
Publication date: 2026/04/08
Hsieh Ming-ShunYang Shu-MinLiao Shu-HuiGoswami ChayanikaWu Pei-HsuanHsiao Tzu-HungChen Yi-MingHu Sung-YuanHow Chorng-KuangLu Tzu-PinChattopadhyay Amrita - Creatine, α-N-methyl-guanidino-acetic acid, plays a fundamental role in the storage and regeneration of high-energy phosphate in the brain. Defects in the creatine transporter gene (CRT/SLC6A8) result in a significant reduction in brain creatine levels and severe neurological symptoms such as intellectual disability. Clarifying creatine dynamics in the brain is essential to increase our understanding of CRT deficiency syndrome (CRTD) pathology and the development of CRTD therapeutics. This review comprehensively summarizes the pathophysiological roles of transporters in dynamics of creatine and related guanidine compounds in the brain barriers and brain parenchyma. Brain creatine dynamics are regulated by the cooperative actions of various influx and efflux transporters of creatine, guanidinoacetate, creatinine, and creatine biosynthetic enzymes. These transporters include CRT/SLC6A8 as a creatine/guanidinoacetate/creatinine influx transporter, MCT12/SLC16A12, and SLC22A15 for creatine efflux transport, TauT/SLC6A6, GAT2/SLC6A13, and GAT3/SLC6A11 for guanidinoacetate influx transport, and OCT3/SLC22A3 for creatinine influx transport. Transporters and creatine biosynthetic enzymes, such as arginine-glycine amidinotransferase and guanidinoacetate N-methyltransferase, exhibit cell-type specific spatio-temporal expression at the brain barrier and in neurons, astrocytes, and oligodendrocytes. To date, no effective therapeutics have been developed for the treatment of CRTD. The link between low brain creatine level and the mechanism of neurological dysfunction remains unclear. Creatine prodrugs, molecular chaperones, and adeno-associated virus-based gene therapies are potential therapeutic options for CRTD. Advanced technologies, such as omics and genetic engineering, will open new avenues for CRTD therapeutics. - Source: PubMed
Tachikawa Masanori - Heart failure (HF) affects over 64 million individuals worldwide and is strongly associated with cognitive impairment (CI), yet the underlying mechanisms remain poorly understood. Here, we identify solute carrier family 22 member 3 (SLC22A3) might be a candidate gene for HF-induced CI through Mendelian randomization and bioinformatics analysis. To investigate its functional role in vivo, we established a mouse model of HF after myocardial infarction (MI). Cognitive performance was evaluated using the Morris water maze. Expression of SLC22A3, blood-brain barrier (BBB) integrity, and neuroinflammatory signalling were examined via immunofluorescence and Western blotting. The involvement of the HA/H1R/NLRP3 signalling pathway was further evaluated using cardiac-specific SLC22A3 overexpression mice, hippocampal-specific H1R knockdown mice, NLRP3 knockout mice, and BV2 cell assays. Consistent with the findings in HF patients, cardiac SLC22A3 expression was dramatically downregulated in HF mice, accompanied by an increase in peripheral histamine (HA) levels, while HA levels in the mouse brain were also significantly raised. Using cardiac-specific SLC22A3 overexpression in HF mice, we demonstrated that restoring SLC22A3 reduced HA accumulation and improved cognitive performance. Mechanistically, HA breached the compromised BBB in HF mice, activating hippocampal microglia H1 receptor (H1R) and the NLRP3 inflammasome. In BV2 cells, HA stimulation elevated NLRP3 expression in a dose-dependent manner, an effect blocked by H1R antagonist. Knockdown of H1R or NLRP3 in the hippocampus attenuated neuroinflammation and rescued HF-induced CI. Our findings unveil a novel cardio-neuroinflammatory axis driven by SLC22A3 deficiency, highlighting HA/H1R/NLRP3 pathway as a therapeutic target for HF-induced CI. - Source: PubMed
Publication date: 2026/03/12
Wang ZhitianZhou LvZhao NaLi TianxiaoGeng FanKong JingtingZhang YahaoZhang ZhijunRen Qing-Guo - Growing evidence implicates solute carrier (SLC) superfamily in atherosclerosis (AS) pathogenesis. This study identified SLC22A3 as a novel AS biomarker and therapeutic target using multi-omics analysis. Integrating WGCNA and machine learning (LASSO, SVM-RFE, XGBoost, Random Forest) on bulk RNA-seq (GSE43292) pinpointed SLC22A3. External datasets (GSE28829, GSE163154) confirmed significant SLC22A3 downregulation in AS (P < 0.001) and high diagnostic accuracy (AUC > 0.9). SMR analysis revealed a causal genetic link between SLC22A3 expression and reduced AS risk (P < 0.05, OR = 0.512 (95% CI: 0.280-0.939))). scRNA-seq showed SLC22A3 specifically expressed in smooth muscle cells (SMCs), significantly reduced in symptomatic patients. Molecular docking and molecular dynamics simulation nominated six FDA-approved drugs as potential SLC22A3-targeting therapeutics. Experimental validation further confirmed the significant downregulation of SLC22A3 at both mRNA and protein levels. SLC22A3 is a promising diagnostic biomarker and therapeutic target for AS, functionally linked to SMCs. - Source: PubMed
Publication date: 2026/03/10
Yu YongchaoWang LanWang TianhuiZhang YaSu XiaomengDai XingyangMo Xiangang - While proton pump inhibitors (PPIs) show epidemiological associations with gastrointestinal disorders, their mechanistic basis remains unclear. The pharmacological effects of a drug are determined not only by its direct protein targets but also by genes involved in its metabolism and transport. Using two-sample Mendelian randomization and multi-ancestry cohorts (UKB/FinnGen), we systematically assessed genes encoding both direct targets of PPIs and key proteins involved in PPI pharmacokinetics across 24 gastrointestinal diseases. Validation included colocalization/SMR analyses, disease stratification, anatomical stratification, and HPA-based tissue expression profiling. Single-cell sequencing further elucidated target distribution. Finally, meta-analysis validates the correlation between PPI and gastrointestinal disorders. CYP2D6 emerged as the most pleiotropic locus (nine disease endpoints), demonstrating dose-dependent carcinogenic effects in hepatocellular/pancreatic cancers (OR = 1.36-1.58, p = 8.45 × 10, OR = 1.43-1.56, p = 2.31 × 10) yet protective against acute/chronic pancreatitis (OR = 0.72-0.75, p = 1.26 × 10, OR = 0.62-0.67, p = 1.39 × 10). ABCB1/SLC22A1 exhibited pan-gastrointestinal risk modulation. Anatomical stratification revealed context-dependent gene effects: SLC22A1 (esophageal), CYP2D6 (hepatic), and CYP2C19 (colorectal) showed opposing roles in carcinogenesis versus precancerous states. HPA profiling identified SLC22A3 as a pan-cancer candidate (moderate-high expression in 4 tumor types). Single-cell tumor data indicated AHR was enriched in tumor cells and significantly higher than in normal cells in all five tumor tissues. The finding suggests that AHR may be related to the potential gastrointestinal carcinogenicity of PPIs. The meta-analysis confirms a significant link between PPI use and increased gastrointestinal cancer risk. Further research is needed on PPI and benign gastrointestinal diseases. Our multi-omics integration reveals tissue-specific PPI pharmacodynamics, identifying targets with dual therapeutic/carcinogenic potential that may explain epidemiological discordances. - Source: PubMed
Zhu WeixiongFan ChuanleiWang HongyuShi RunYang ZengxiQin JianqiZhao YongqinMu YanxiLi MingCheng YushengZhou Wence