Ask about this productRelated genes to: KCNH3 Blocking Peptide
- Gene:
- KCNH3 NIH gene
- Name:
- potassium voltage-gated channel subfamily H member 3
- Previous symbol:
- -
- Synonyms:
- Kv12.2, BEC1, elk2
- Chromosome:
- 12q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 1999-12-14
- Date modifiied:
- 2016-10-11
Related products to: KCNH3 Blocking Peptide
Related articles to: KCNH3 Blocking Peptide
- A de novo missense variant in has been identified in a patient with neurological symptoms including seizures. Here, we confirm the previously reported loss-of-function features for the associated Kv12.2 mutant A371V and investigate the underlying mechanism. Loss of function was not rescued by low temperature during channel biogenesis. Elevated external K reduced the rectification of Kv12.2 conductance as predicted by the GHK current equation, allowing the detection of currents mediated by homomeric A371V Kv12.2 channels and a detailed biophysical analysis of the mutant. Compared to wild-type, the voltage dependences of activation and deactivation of A371V Kv12.2 channels were shifted in the positive direction by 15 to 20 mV. Moreover, A371V Kv12.2 channels exhibited accelerated inactivation kinetics combined with a dramatic negative shift in the voltage dependence of inactivation by more than 100 mV. Even in heteromeric wild-type + A371V Kv12.2 channels, inactivation was enhanced, leading to a significant current reduction at physiological potentials. Our Kv12.2 data show similarities to Kv11 channels regarding C-type inactivation and differences regarding the sensitivity to external K and pharmacological inhibition of inactivation. The gating modification caused by the A371V amino acid substitution in Kv12.2 renders loss of function voltage-dependent, with a possible impact on neuronal excitability and firing behavior. - Source: PubMed
Publication date: 2025/05/13
Bauer Christiane KBilet ArneHarms Frederike LBähring Robert - The Sahiwal are among the most prominent international transboundary dairy cattle distributed in large numbers between India and Pakistan. With the elapse of more than seven decades after the independence and limited cross-border exchange of Sahiwal germplasm, one thought-provoking question arises as to whether natural and artificial selection could alter the genomic signature patterns in the Sahiwal, reared for different purposes in these two countries. Deciphering the genetic mechanisms that underlie economic traits is essential for advancement and long-term breeding plans that are reflected in the distinct selection signatures they carry. To identify these genomic signatures, three medium-density SNP datasets of Sahiwal from three geographical locations of India and Pakistan were analyzed, using De-Correlated Composite of Multiple Selection Signals technique to identify the major candidate genes. In the genome of Sahiwal, a total of 70 genomic regions with 261 protein-coding genes were found. Milk production (NEK11, HMGCS1, BTN1A1,KCNH3), reproduction (SH3BGR, PSMG1, BRWD1,B3GALT5) and immune response genes (BPIFB1, MCOLN2) were more closely related to the Indian Sahiwal. Pakistani Sahiwal had genes closely linked with the dual-purpose meat (RALGAPA2, RIN2, CFAP61), and milk (SLC24A3 GALNT17, BACH2) traits. Our findings revealed differential patterns of selection signatures in transboundary Sahiwal cattle. - Source: PubMed
Publication date: 2025/05/05
Muansangi LalTiwari JigyashaIlayaraja IrusappanKumar IshmeetVyas JayeshChitra AnilSingh Sanchit PalPal PritamGowane GopalMishra A KMukherjee AnupamaMukherjee Sabyasachi - The KCNH gene family encodes voltage-gated potassium (Kv) channels of the EAG subtype covering three subfamilies (Kv10-12). EAG channels are involved in the control of cardiac and neuronal excitation, and pathogenic variants in KCNH genes encoding Kv10 (eag) and Kv11 (erg) subfamily members cause a broad clinical spectrum ranging from cardiac arrhythmia to neurodevelopmental syndromes. However, no pathogenic variants have been hitherto reported for KCNH genes encoding Kv12 (elk) subfamily members. - Source: PubMed
Publication date: 2025/03/20
Bauer Christiane KKortüm FannyMöllring AnnaGrinstein LevDenecke JonasAlawi MalikBähring RobertHarms Frederike L - Transducin β-like 1 X-linked receptor 1 (mouse Tbl1xr1) or TBL1X/Y related 1 (human TBL1XR1), part of the NCoR/SMRT corepressor complex, is involved in nuclear receptor signaling. Variants in TBL1XR1 cause a variety of neurodevelopmental disorders including Pierpont syndrome caused by the p.Tyr446Cys variant. We recently reported a mouse model carrying the Tbl1xr1 variant as a model for Pierpont syndrome. To obtain insight into mechanisms involved in altered brain development we studied gene expression patterns in the cortex of mutant and wild type (WT) mice, using RNA-sequencing, differentially expressed gene (DEG) analysis, gene set enrichment analysis (GSEA), weighted gene correlation network analysis (WGCNA) and hub gene analysis. We validated results in mutated mouse cortex, as well as in BV2 and SK-N-AS cell lines, in both of which Tbl1xr1 was knocked down by siRNA. Two DEGs (adj.P. Val < 0.05) were found in the cortex, Mpeg1 (downregulated in mutant mice) and 2900052N01Rik (upregulated in mutant mice). GSEA, WGCNA and hub gene analysis demonstrated changes in genes involved in ion channel function and neuroinflammation in the cortex of the Tbl1xr1 mice. The lowered expression of ion channel genes Kcnh3 and Kcnj4 mRNA was validated in the mutant mouse cortex, and increased expression of TRIM9, associated with neuroinflammation, was confirmed in the SK-N-AS cell line. Conclusively, our results show altered expression of genes involved in ion channel function and neuroinflammation in the cortex of the Tbl1xr1 mice. These may partly explain the impaired neurodevelopment observed in individuals with Pierpont syndrome and related TBL1XR1-related disorders. - Source: PubMed
Publication date: 2024/06/15
Hu YalanLauffer PeterJongejan AldoFalize KimBruinstroop Evelinevan Trotsenburg PaulFliers EricHennekam Raoul CBoelen Anita - Treatment resistance remains a major issue in aggressive prostate cancer (PC), and novel genomic biomarkers may guide better treatment selection. Circulating tumor DNA (ctDNA) can provide minimally invasive information about tumor genomes, but the genomic landscape of aggressive PC based on whole-genome sequencing (WGS) of ctDNA remains incompletely characterized. Thus, we here performed WGS of tumor tissue (n = 31) or plasma ctDNA (n = 10) from a total of 41 aggressive PC patients, including 11 hormone-naïve, 15 hormone-sensitive, and 15 castration-resistant patients. Across all variant types, we found progressively more altered tumor genomic profiles in later stages of aggressive PC. The potential driver genes most frequently affected by single-nucleotide variants or insertions/deletions included the known PC-related genes TP53, CDK12, and PTEN and the novel genes COL13A1, KCNH3, and SENP3. Etiologically, aggressive PC was associated with age-related and DNA repair-related mutational signatures. Copy number variants most frequently affected 14q11.2 and 8p21.2, where no well-recognized PC-related genes are located, and also frequently affected regions near the known PC-related genes MYC, AR, TP53, PTEN, and BRCA1. Structural variants most frequently involved not only the known PC-related genes TMPRSS2 and ERG but also the less extensively studied gene in this context, PTPRD. Finally, clinically actionable variants were detected throughout all stages of aggressive PC and in both plasma and tissue samples, emphasizing the potential clinical applicability of WGS of minimally invasive plasma samples. Overall, our study highlights the feasibility of using liquid biopsies for comprehensive genomic characterization as an alternative to tissue biopsies in advanced/aggressive PC. - Source: PubMed
Publication date: 2024/04/11
Weiss SimoneLamy PhilippeRusan MariaNørgaard MaibrittUlhøi Benedicte ParmKnudsen MichaelKassentoft Christine GaasdalFarajzadeh LeilaJensen Jørgen BjerggaardPedersen Jakob SkouBorre MichaelSørensen Karina Dalsgaard