Ask about this productRelated genes to: CLCNKA Blocking Peptide
- Gene:
- CLCNKA NIH gene
- Name:
- chloride voltage-gated channel Ka
- Previous symbol:
- -
- Synonyms:
- hClC-Ka
- Chromosome:
- 1p36.13
- Locus Type:
- gene with protein product
- Date approved:
- 1995-12-11
- Date modifiied:
- 2016-02-04
Related products to: CLCNKA Blocking Peptide
Related articles to: CLCNKA Blocking Peptide
- Cardiac dysfunction is a prevalent feature of multiple cardiovascular diseases, driven by a complex genetic architecture coordinating structural and functional traits. However, systematic dissection of multidimensional cardiac function phenotypes remains scarce, highlighting the need for integrative models to uncover shared genetic mechanisms. We combined genome-wide association study (GWAS) summary statistics for six cardiac phenotypes—left ventricular ejection fraction (LVEF), left ventricular stroke volume (LVSV), longitudinal and radial myocardial strain (LS, RS), right ventricular ejection fraction (RVEF), and N-terminal pro-B-type natriuretic peptide (NT-proBNP). Multivariate Linkage Disequilibrium Score regression estimated their genetic covariance, and a Genomic Structural Equation Model (Genomic-SEM) extracted latent genetic factors. Transcriptome-wide association studies (TWAS), fine-mapping, and functional enrichment identified key susceptibility loci and genes. We further integrated AlphaFold3-based structural prediction, molecular dynamics simulations, and AI-driven thermodynamic stability assessment to evaluate the functional consequences of pathogenic variants. Genomic-SEM identified a robust latent factor explaining genetic covariation across phenotypes. GWAS and fine-mapping pinpointed six potential causal loci, while TWAS identified 29 significant genes enriched in cardiac contraction, calcium signaling, and mitochondrial pathways. CLCNKA emerged as a critical gene; molecular dynamics revealed its mutations disrupt protein conformation, increase flexibility, and reduce thermal stability, suggesting pathogenic potential. This study provides the first comprehensive genetic architecture of latent cardiac function phenotypes. Integrating Genomic-SEM with AI-assisted structural analysis identified novel loci and elucidated mutation-driven functional disruptions, offering insights into genetic regulation of cardiac function and guiding precision medicine strategies. - Source: PubMed
Publication date: 2026/01/28
Li XiaolinQin Yalu - Bartter syndrome (BS) is an autosomal recessive disorder characterized by polyhydramnios, premature birth, polyuria, renal salt-wasting, hypokalemic metabolic alkalosis, normal blood pressure with increased levels of renin and aldosterone, and the presence of hearing loss. Mutations in BSND, CLCNKA, and CLCNKB cause the disorder. We present a 3-year-old girl with BS type 4 and sensorineural hearing loss who received cochlear implantation (CI) after failing a hearing screening. The patient had a successful left-side implantation but later developed a flap infection, initially treated with antibiotics and surgical repair using a vascularized flap, which failed. During the same repair procedure, the right ear was implanted successfully. A third surgery was required to remove the left implant and close the wound with a temporoparietal flap, performed by plastic surgery. This is the earliest report on managing device extrusion in BS. The literature review highlights that the outcomes of CI in patients with BS vary significantly within each syndrome group and that the presence of additional disabilities accentuates this diversity. Our case illustrates that CI can improve the quality of life for patients with BS, but a multidisciplinary team is crucial for managing these cases. We stress the need for further studies to evaluate realistic outcomes and complication rates, as this will guide future treatment strategies. - Source: PubMed
Publication date: 2025/07/01
Badr Khalid MRaza Syed AAlahmadi AsmaAlghamdi FaresThabet Alsaeid MAlghamdi Saeed - The ClC-K channels and are crucial for the transepithelial transport processes required for sufficient urinary concentrations and sensory mechanoelectrical transduction in the cochlea. Loss-of-function alleles in these channels are associated with various clinical phenotypes, ranging from hypokalemic alkalosis to sensorineural hearing loss (SNHL) accompanied by severe renal conditions, i.e., Bartter's syndrome. Using a stepwise genetic approach encompassing whole-genome sequencing (WGS), we identified one family with compound heterozygous variants in the ClC-K channels, specifically a truncating variant in in trans with a contiguous deletion of and . Breakpoint PCR and Sanger sequencing elucidated the breakpoint junctions derived from WGS, and allele-specific droplet digital PCR confirmed one copy loss of the _ contiguous deletion. The proband that harbors the variants is characterized by SNHL without hypokalemic alkalosis and renal anomalies, suggesting a distinct phenotype in the ClC-K channels in whom SNHL predominantly occurs. These results expanded genotypes and phenotypes associated with ClC-K channels, including the disease entities associated with non-syndromic hearing loss. Repeated identification of deletions across various extents of suggests a mutational hotspot allele, highlighting the need for an in-depth analysis of the intergenic region, especially in undiagnosed SNHL patients with a single hit in . - Source: PubMed
Publication date: 2023/12/03
Yun YejinPark Sang SooLee SoyoungSeok HeeyoungPark SeongyeolLee Sang-Yeon - Long-read sequencing is increasingly used to uncover structural variants in the human genome, both functionally neutral and deleterious. Structural variants occur more frequently in regions with a high homology or repetitive segments, and one rearrangement may predispose to additional events. Bartter syndrome type 3 (BS 3) is a monogenic tubulopathy caused by deleterious variants in the chloride channel gene CLCNKB, a high proportion of these being large gene deletions. Multiplex ligation-dependent probe amplification, the current diagnostic gold standard for this type of mutation, will indicate a simple homozygous gene deletion in biallelic deletion carriers. However, since the phenotypic spectrum of BS 3 is broad even among biallelic deletion carriers, we undertook a more detailed analysis of precise breakpoint regions and genomic structure. - Source: PubMed
Publication date: 2023/08/23
Tschernoster NikolaiErger FlorianKohl StefanReusch BjörnWenzel AndreaWalsh StephenThiele HolgerBecker ChristianFranitza MarekBartram Malte PKömhoff MartinSchumacher LenaKukat ChristianBorodina TatianaQuedenau ClaudiaNürnberg PeterRinschen Markus MDriller Jan HPedersen Bjørn PSchlingmann Karl PHüttel BrunoBockenhauer DetlefBeck BodoAltmüller Janine - Disease severity of autosomal dominant polycystic kidney disease (ADPKD) is influenced by diet. Dietary protein, a recognized cyst-accelerating factor, is catabolized into amino acids (AA) and delivered to the kidney leading to renal hypertrophy. Injury-induced hypertrophic signaling in ADPKD results in increased macrophage (MФ) activation and inflammation followed by cyst growth. We hypothesize that the cystogenesis-prompting effects of HP diet are caused by increased delivery of specific AA to the kidney, ultimately stimulating MФs to promote cyst progression. - Source: PubMed
Publication date: 2023/07/19
Sedaka RandeeHuang JifengYamaguchi ShinobuLovelady CalebHsu Jung-ShanShinde SejalKasztan MalgorzataCrossman David KSaigusa Takamitsu