Ask about this productRelated genes to: KCNN2 Blocking Peptide
- Gene:
- KCNN2 NIH gene
- Name:
- potassium calcium-activated channel subfamily N member 2
- Previous symbol:
- -
- Synonyms:
- KCa2.2, hSK2
- Chromosome:
- 5q22.3
- Locus Type:
- gene with protein product
- Date approved:
- 1998-04-07
- Date modifiied:
- 2016-02-04
Related products to: KCNN2 Blocking Peptide
Related articles to: KCNN2 Blocking Peptide
- Myoclonus-dystonia syndrome (MDS) is a clinically and genetically heterogeneous movement disorder characterized by myoclonus and dystonia as its core features. While mutations in the sarcoglycan gene (SGCE) account for most familial cases, heterozygous pathogenic variants in and have recently been described as novel genetic causes of MDS. e describe three patients from two Polish families presenting with progressive movement disorder combined with other features. Exome sequencing (ES) identified a novel heterozygous variant c.461 T > A, p.(Met154Lys) in a five-year-old girl with abnormal gait, postural instability, myoclonus, and tongue dyskinesia. In a 38-year-old woman and her 17-year-old daughter, both showing tremor, myoclonus, dystonia, and psychiatric symptoms, ES detected a heterozygous canonical splice-site c.1780-2A > G variant in . Neuropsychological evaluation suggested a gene-specific effect of on psychiatric and cognitive functioning, including significant episodic memory impairment. This study broadens the clinical and molecular spectrum of - and -related MDS and highlights distinctive features compared with -MDS, focusing on disease progression, treatment response, and neuropsychiatric involvement. Recognition of these patterns may guide molecular diagnosis and the management of specific MDS types. - Source: PubMed
Publication date: 2026/03/30
Krygier MagdalenaSitek Emilia JChylińska MagdalenaZiętkiewicz SzymonZawadzka MartaDulski JarosławSchinwelski MichałKostrzewa GrażynaWierzba JolantaPłoski RafałZech MichaelMazurkiewicz-Bełdzińska Maria - Preterm infants frequently sustain brief hypoxic insults of unclear clinical significance. Since preterm survivors commonly sustain lifelong memory impairment without apparent gray matter injury, we tested whether mild hypoxia alone without ischemia could persistently disrupt adult hippocampal learning and memory mechanisms without causing brain injury. We developed a neonatal mouse model of mild hypoxia that generated clinically relevant oxygen desaturation, but without responses typically associated with hypoxia-ischemia including bradycardia, seizures, neuroinflammation, and neuronal or glial degeneration. RNA transcriptomic studies identified that expression of immature hippocampal synaptic components was broadly targeted by mild hypoxia. Neonatal hypoxia resulted in hippocampal learning and memory deficits and abnormal maturation of CA1 (cornu ammonis 1) neurons that persisted into adulthood. Memory deficits were accompanied by reduced adult hippocampal CA3→CA1 synaptic strength and LTP and abolished synaptic activity of calcium-sensitive SK2 (small conductance Ca -activated potassium) channels, a regulator of spike timing-dependent neuroplasticity, including LTP and memory encoding. Structural illumination microscopy revealed reduced synaptic density without altered synaptic SK2 distribution. Persistent loss of SK2 activity was mediated by increased CK2 phosphorylation of synaptic calmodulin and restored by CK2 blockade. Clinically relevant mild hypoxia in neonatal mice is thus sufficient to disrupt hippocampal maturation into adulthood independently of cerebral gray or white matter injury and trigger persistent loss of synaptic SK2 channel activity that disrupts excitatory synaptic function. Our findings suggest that neonatal hypoxia contributes to the broad spectrum of neurobehavioral, cognitive, and learning disabilities that paradoxically persist into adulthood without overt gray matter injury in preterm survivors. - Source: PubMed
Publication date: 2026/04/22
Riddle ArtSrivastava TaasinWang KangTellez EduardoO'Neill HannaGong XiO'Niel AbigailBell Jaden ARaber JacobLattal MatthewMaylie JamesBack Stephen A - Liver fibrosis (LF) is a progressive pathological process that may lead to cirrhosis and liver failure. Human ion channel genes (HICGs) participate in hepatic mechanotransduction and immune regulation, but their contributions to LF remain insufficiently characterized. This study aimed to profile the expression of HICGs in LF and to identify key genes with diagnostic and therapeutic relevance. - Source: PubMed
Publication date: 2026/02/16
Li YunShen DuoerQin FushengChen DongkuiLi Jianguo - The small-conductance calcium-activated potassium (SK1-3 or K2) channels regulate the intrinsic excitability and firing frequency of excitable cells. SK channels are modulated by a variety of distinct modulators; however, the underlying mechanisms remain elusive. Here, we present four cryoelectron microscopy structures of the human SK2-calmodulin complex bound with apamin, UCL1684, AP30663, and CAD-1883, elucidating their distinct binding sites and regulatory mechanisms. Apamin and UCL1684 compete for a similar binding site above the selectivity filter, which is formed by the distinct S3-S4 linker of SK2. CAD-1883 glues the N-lobe of calmodulin and the S4-S5 linker of SK2, reinforcing the open state. In contrast, AP30663 resides in the central cavity of SK2, blocking ion conductance. This study reveals multiple modulation sites in SK2 and the molecular mechanisms for the inhibition and potentiation of SK channels, which could advance rational drug design targeting SK2 channel for the treatment of cardiovascular and neurological disorders. - Source: PubMed
Publication date: 2026/01/15
Ma BaoWu DiCao EnChi ChengWang ZhihaoXia ZhanyiSun Long-HuaPan BingxingJiang DaohuaZhang Wenhua - Small-conductance (K2.2) and intermediate-conductance (K3.1) Ca-activated K channels are gated by a Ca-calmodulin dependent mechanism. NS309 potentiates the activity of both K2.2 and K3.1, while rimtuzalcap selectively activates K2.2. Rimtuzalcap has been used in clinical trials for the treatment of spinocerebellar ataxia and essential tremor. We report cryo-electron microscopy structures of NS309-bound K2.2 and K3.1, in addition to structures of rimtuzalcap-bound K2.2 and mutant K3.1_R355K. The different conformations of calmodulin and the cytoplasmic HC helices in the two channels underlie the subtype-selectivity of rimtuzalcap for K2.2. NS309 binds to pre-existing pockets in both channels, while the bulkier rimtuzalcap binds in an induced-fit pocket in K2.2 requiring conformational changes. In K2.2, calmodulin's N-lobes are sufficiently far apart to enable conformational changes to accommodate either NS309 or rimtuzalcap. In K3.1, calmodulin's N-lobes are closer to each other and constrained by K3.1's HC helices, which allows binding of NS309 but not rimtuzalcap. Replacement of arginine-355 in K3.1's HB helix with lysine (K3.1_R355K) allows the binding of rimtuzalcap and renders the mutant channel sensitive to rimtuzalcap. These structures provide a framework for structure-based drug design targeting K2.2 channels. - Source: PubMed
Publication date: 2026/01/08
Nam Young-WooRamanishka AlenaXu YangYasuda Rose Marie HaynesNasburg Joshua AIm DohyunCui MengChandy K GeorgeWulff HeikeZhang Miao