Ask about this productRelated genes to: KCNJ5 antibody
- Gene:
- KCNJ5 NIH gene
- Name:
- potassium voltage-gated channel subfamily J member 5
- Previous symbol:
- -
- Synonyms:
- Kir3.4, CIR, KATP1, GIRK4, LQT13
- Chromosome:
- 11q24.3
- Locus Type:
- gene with protein product
- Date approved:
- 1995-04-13
- Date modifiied:
- 2019-04-23
Related products to: KCNJ5 antibody
Related articles to: KCNJ5 antibody
- Antibiotics are widely used in clinical practice, yet their potential effects on endocrine homeostasis remain insufficiently recognized. This review summarizes endocrine adverse effects associated with selected antibacterial agents, their proposed mechanisms, and clinical relevance. - Source: PubMed
Publication date: 2026/09/02
Grabarczyk ŁukaszOszytko JuliaDerkaczew MariaSobolewski KamilRadkowski Paweł - Primary aldosteronism (PA) is one of the most common causes of secondary hypertension, with aldosterone-producing adenomas (APAs) accounting for approximately half of cases. In most APAs, somatic mutations in ion channel or pump genes constitutively activate Ca signaling through membrane depolarization, driving overexpression of the aldosterone synthase CYP11B2 and excess aldosterone production. Although KCNJ5 mutations represent the most prevalent somatic driver of APA pathogenesis, existing pharmacotherapies-including mineralocorticoid receptor antagonists (MRAs) and CYP11B2 enzyme inhibitors-have limitations in efficacy and selectivity, and are associated with notable adverse effects, indicating an urgent need for novel strategies that suppress CYP11B2 expression at the transcriptional level through a distinct mechanism of action. To address this need, we performed high-throughput screening of a compound library using a KCl stimulation-dependent CYP11B2 reporter system, with multi-step filtering incorporating cytotoxicity evaluation and validation in doxycycline-inducible KCNJ5-L168R mutant-expressing cells. This approach identified compound 35 (2-benzylidene-5-allyladamantan-1-ol) as a lead candidate. Compound 35 suppressed CYP11B2 mRNA expression and aldosterone secretion in KCNJ5-L168R mutant cells without inhibiting KCl-induced Ca influx, demonstrating that its mechanism of action lies downstream of Ca entry. Compound 35 also reduced NURR1 and NGFIB expression, pointing to a mechanism upstream of NR4A-dependent CYP11B2 induction. Notably, compound 35 showed no significant effect on CYP11B1 mRNA expression, suggesting selectivity at the transcriptional level that is mechanistically distinct from the structural similarity-based selectivity challenges faced by CYP11B2 enzyme inhibitors. These results identify compound 35 as a chemically tractable lead with a mechanism of action distinct from MRAs, Ca channel blockers, and CYP11B2 enzyme inhibitors, providing a starting point for the development of transcriptional suppressors of CYP11B2 as a novel therapeutic strategy for KCNJ5 mutation-associated PA. - Source: PubMed
Publication date: 2026/09/12
Otsubo YuriShimada HirokiHoshi KeitaIto RyoNguyen Thanh PhuongYamakoshi HiroyukiOhsawa KosukeUeda HirofumiTokuyama HidetoshiSaito YoshiroIwabuchi YoshiharuDoi TakayukiNakamura YasuhiroSugawara AkiraYokoyama Atsushi - Circulating tumor DNA (ctDNA) can be detected in adrenocortical carcinoma; however, its detectability in benign adrenal tumors, such as aldosterone-producing adenoma (APA), remains unclear. We investigated whether tumor-specific mutations could be detected in plasma cell-free DNA (cfDNA) obtained from peripheral and adrenal venous blood in a 34-year-old man with APA. The patient was evaluated for secondary hypertension, and screening and confirmatory tests established the diagnosis of primary aldosteronism. Computed tomography revealed an 11-mm left adrenal mass, and adrenal venous sampling demonstrated left-sided aldosterone hypersecretion. The patient subsequently underwent left adrenalectomy, and pathological examination confirmed an APA. Targeted next-generation sequencing of 18 adrenal disease-related genes identified a somatic mutation in the tumor tissue. However, the corresponding mutation was not detectable in cfDNA from either peripheral or adrenal venous plasma, despite sampling under clinically favorable conditions. Postoperatively, blood pressure and serum potassium levels normalized. This case illustrates the challenges of detecting tumor-derived mutations in plasma from small benign adrenal tumors using standard sequencing approaches and highlights how tumor burden, sampling conditions, and assay sensitivity influence ctDNA detectability. Further studies employing highly sensitive, mutation-targeted methods are warranted to elucidate the biological and technical factors affecting ctDNA detection in APA. - Source: PubMed
Publication date: 2026/08/28
Aono DaisukeKato ToshiakiKometani MitsuhiroYoneda TakashiHosomichi KazuyoshiKarashima Shigehiro - Primary aldosteronism (PA), the most common curable form of hypertension, is frequently caused by aldosterone-producing adenomas (APAs) harbouring KCNJ5 mutations that render aldosterone synthesis sensitive to macrolides in vitro. This study aimed to evaluate whether a single dose of roxithromycin reduces plasma aldosterone concentration (PAC) and blood pressure (BP) in patients with KCNJ5-mutated APA, and to characterize the haemodynamic effects of macrolides in mice. - Source: PubMed
Rossi Gian PaoloCaroccia BrasilinaBressan AlessandroByiringiro ClementGarcía-Redondo Ana BelénCeolotto GiulioZanotti GiuseppePadrini RobertoBriones Ana MariaSeccia Teresa Maria - Primary aldosteronism (PA) is a common, under-recognised cause of hypertension carrying cardiovascular and renal risk beyond blood pressure alone. Management requires accurate subtype diagnosis: lateralised disease may be cured by adrenalectomy, whereas bilateral disease usually requires mineralocorticoid receptor antagonist therapy. The PASO criteria standardised postsurgical outcome assessment and showed that biochemical remission is achieved in most patients with adrenal vein sampling-confirmed lateralised disease, whereas clinical remission is variable, reflecting pre-existing hypertensive burden, age and sex. The PAMO criteria extend this framework to medically treated PA and show that complete clinical response is uncommon. At the tissue level, the HISTALDO classification distinguishes classical lateralised disease, typically caused by an aldosterone-producing adenoma, from non-classical disease, dominated by multiple micronodules; the latter carries a higher risk of postsurgical persistent or recurrent aldosteronism. These observations support a broader model in which PA forms a continuous rather than binary spectrum, from subclinical renin-independent aldosteronism and age-related micronodular remodelling to overt bilateral and lateralised disease. Tissue omics studies support a model in which aldosterone-producing lesions progress from zona glomerulosa cells to micronodules and adenomas. KCNJ5-mutated adenomas may follow a direct route, arising without a detectable micronodule stage, possibly because reduced oxidative stress favours early cell survival and expansion. The adenoma is therefore not a static endpoint but a maturing tissue, in which immune remodelling and changes in cell survival mechanisms may shape progression towards a hypersecretory state. Together, these findings link clinical phenotype to adrenal tissue biology and support a dynamic, genotype-modulated model of PA pathogenesis. - Source: PubMed
Wei JiaWilliams Tracy Ann