Slc12a5 siRNA_Lentivectors
- Known as:
- Slc12a5 siRNA_Lentivectors
- Catalog number:
- i064664c
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- Slc12a5 siRNA_Lentivectors
Related genes to: Slc12a5 siRNA_Lentivectors
- Gene:
- SLC12A5 NIH gene
- Name:
- solute carrier family 12 member 5
- Previous symbol:
- -
- Synonyms:
- KIAA1176, KCC2
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2000-11-09
- Date modifiied:
- 2016-02-17
Related products to: Slc12a5 siRNA_Lentivectors
Related articles to: Slc12a5 siRNA_Lentivectors
- The potassium-chloride cotransporter 2 (KCC2) is a neuron-specific transporter essential for maintaining low intracellular chloride levels. By extruding chloride ions, KCC2 ensures that activation of GABA receptors produces hyperpolarizing inhibitory responses rather than depolarizing responses. Disruption of KCC2 function can therefore impair GABAergic signaling and neuronal maturation, contributing to a range of neurodevelopmental and neurological disorders. Pathogenic biallelic variants in SLC12A5, the gene encoding KCC2, are a rare cause of severe early-onset developmental and epileptic encephalopathies, including epilepsy of infancy with migrating focal seizures (EIMFS). Here, we describe a novel homozygous SLC12A5 variant identified in a patient with severe, drug-resistant epilepsy, neonatal encephalopathy, and rapid neurological deterioration. Combined Western blot, thallium (Tl) flux, and gramicidin-perforated patch-clamp assays revealed significantly reduced ion-transport function of the KCC2 construct encoding the variant, with no change in protein expression abundance or profile. Live-cell surface immunolabeling demonstrated markedly reduced plasma membrane expression and decreased internalization of the variant, suggesting that the functional deficit primarily results from defective trafficking or reduced membrane stability. These findings expand the spectrum of KCC2-related disorders and highlight the critical role of KCC2 in early brain development. By linking a specific SLC12A5 variant to impaired chloride homeostasis and neuronal hyperexcitability, this study provides mechanistic insight into disease pathogenesis and lays the groundwork for therapeutic strategies aimed at restoring or stabilizing KCC2 function. - Source: PubMed
Publication date: 2026/06/17
Ghalamkari SafouraJӓrvelӓ ViiviHartmann Anna-MariaMerő GabriellaHudák RenátaMótyán János AndrásSzakszon KatalinHuttula MarkoUusimaa JohannaImmonen Esa-VilleMedina IgorBalogh Istvan - Allele-specific expression (ASE), preferential expression of one allele at a heterozygous locus, is implicated in various brain diseases but remains largely uncharacterized in Alzheimer's disease (AD). - Source: PubMed
Wang ZishanHossain DelowarWang Judy JiaruSubramaniam Varun RZhang BinWang MinghuiHuang Kuan-Lin - Clear cell renal cell carcinoma (ccRCC) is an angiogenic tumor originating from proximal tubule epithelial cells. Ammonia induced cell death is closely associated with carcinogenesis, but its potential mechanism in ccRCC remains unclear and requires further investigation. - Source: PubMed
Publication date: 2026/04/23
Jiang YaoZhang TianFan JieSu YanshengQiao ShaoyiJi JintaoHu XiangnanZhou ShuchangWei YingjuanDu LinaYang BoZhang Wuhe - This study was undertaken to characterize the functional impact of novel SLC12A5 variants in two unrelated patients with early onset developmental and epileptic encephalopathy (DEE) and to investigate the mechanisms underlying KCC2 dysfunction. - Source: PubMed
Publication date: 2026/04/25
Hamze MiraWhitney RobynVille DorothéeVilleneuve NathalieHartmann Anna-MariaBecker LisaHausmann JensZhang JinweiBrier CathyPisella Lucie IFriedel PerrineLabalme AudreyAlix EudelineChatron NicolasSanlaville DamienGory-Fauré SylvieDenarier EricPorcher ChristopheLesca GaetanMedina Igor - The neuronal K/Cl cotransporter KCC2 regulates the transmembrane chloride gradient, which controls the efficacy of GABAergic signaling. In mesial temporal lobe epilepsy (mTLE) and other neurological disorders, reduced KCC2 expression or function can result in depolarizing GABA signaling, which is thought to contribute to pathological activity and seizures. Therefore, restoring chloride homeostasis represents a promising therapeutic strategy. We investigated the mechanisms and antiseizure effects of two small molecules, prochlorperazine (PCPZ) and CLP-257, that have been identified as potential KCC2 enhancers. We found that both compounds enhance KCC2 function and clustering in cortical neurons while reducing its membrane diffusion, without altering canonical regulatory phosphorylation. CLP-257 also selectively increased extrasynaptic, but not synaptic, GABA receptor-mediated currents. Using in vitro recordings from resected brain tissue of patients with drug-resistant mTLE and in vivo recordings from a mouse model, we show that PCPZ and CLP-257 (or its prodrug CLP-290) effectively suppressed spontaneous epileptiform activity in both models. These findings reveal that PCPZ and CLP-257 act as genuine KCC2 enhancers and provide experimental evidence of the therapeutic potential of such compounds for treating drug-resistant mTLE. - Source: PubMed
Publication date: 2026/03/03
Donneger FlorianZanin AdrienBesson JeremyRoussel DelphineKadiri YonessPagan CarlaSinha ManishaDavid NicolasRusseau MarionBielle FranckDevaux BertrandMathon BertrandNavarro VincentChassoux FrancinePoncer Jean Christophe