Ask about this productRelated genes to: SLC12A5 Blocking Peptide
- 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 Blocking Peptide
Related articles to: SLC12A5 Blocking Peptide
- 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 regulation of chloride levels is a crucial part of controlling inhibitory signals, but does not occur uniformly throughout the body. Recent data suggest that chloride is regulated within localized "microdomains" which are defined by the interaction of KCC2 and NKCC1, structural restraints on cells due to their internal structure, the metabolic condition of the cell, and the external environment modified by astrocytes. The gradients of chloride concentrations within these compartment-specific microdomains define the local chloride reversal potential, and thereby determine the directionality (i.e., whether excitatory or inhibitory), magnitude, and timing of GABAergic inhibition. The disruption of this organized chloride gradient within microdomains impairs the stability of inhibitory activity at multiple levels of integration, including dendritic input, spike timing, interneuron synchronization, and network oscillation. Disturbances in inhibitory stability have been found in a variety of diseases, including epilepsy, neonatal seizure, neuropathic pain, and schizophrenia-spectrum disorders. This supports the hypothesis that disturbances in chloride homeostasis lead to a loss of stability in cortical circuits. This review will provide a synthesis of the molecular, spatial, and circuit level principles involved in the regulation of chloride and discuss how failures of these mechanisms produce clinically relevant disturbances in inhibitory signal processing. In addition, we will be discussing new therapeutic strategies for the restoration of chloride homeostasis, including KCC2 repair, selective modulation of NKCC1, targeting astrocytes, and microenvironmental engineering. Overall, the studies reviewed here provide a unified model for understanding the pathophysiology of inhibitory dysfunction, and demonstrate that the regulation of chloride microdomains provides a novel and promising area of research for translational intervention. - Source: PubMed
Publication date: 2026/03/31
Dumitrescu DanOprea StefanTulin RalucaDumitru Adrian VasileMunteanu OctavianPariza George