Ask about this productRelated genes to: KCNQ4 antibody
- Gene:
- KCNQ4 NIH gene
- Name:
- potassium voltage-gated channel subfamily Q member 4
- Previous symbol:
- DFNA2
- Synonyms:
- Kv7.4
- Chromosome:
- 1p34.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-02-05
- Date modifiied:
- 2019-04-23
Related products to: KCNQ4 antibody
Related articles to: KCNQ4 antibody
- The medial olivocochlear (MOC) efferent system modulates outer hair cell (OHC) excitability and protects cochlea from overstimulation. Cholinergic activation of α9α10 nicotinic acetylcholine receptors (nAChRs) triggers Ca⁺ influx, activating BK and SK2 Ca⁺-dependent K⁺ channels, and K⁺ extrusion through KCNQ4 to restore membrane potential. KCNQ4-loss causes chronic depolarization, OHC dysfunction, and hearing loss. Here, we investigated how KCNQ4 deficiency affects cochlear efferent synapse development and organization. Using confocal immunofluorescence, we analyzed efferent innervation in the organ of Corti of Kcnq4 (KO) and Kcnq4 (WT) mice at 2, 3, 4, and 10 postnatal weeks (W). At 2 W, efferent terminals were similarly distributed between basal and lateral OHC membrane domains in both genotypes. During maturation, WT mice exhibited complete relocation of MOC terminals to the basal domain, whereas KO mice showed delayed maturation, with some terminals laterally displaced up to 10 W. KCNQ4 absence was associated with reduced number and volume of synaptic vesicles per efferent boutons on OHCs. Milder morphometric alterations were observed in efferent boutons within the inner hair cell region. At the molecular level, qPCR revealed downregulation of α10 nAChR subunit, BK, and SK2 transcripts in KO at 4 W, with recovery to 10 W. Despite this recovery, BK protein showed reduced expression, mislocalization, and disorganized synaptic plaques in OHCs. KO also displayed age-dependent upregulation of the calcium-binding proteins calbindin and calretinin, suggesting compensatory responses to altered Ca homeostasis. Together, these findings demonstrate that KCNQ4 is essential for OHC repolarization, maturation and maintenance of cochlear efferent synapses. - Source: PubMed
Publication date: 2026/05/01
Rías EzequielOuwerkerk IngridSpitzmaul GuillermoDionisio Leonardo - Approximately 200 genes have been identified as causative in hereditary hearing loss. Genetic testing is increasingly important, not only for accurate diagnosis but also for predicting audiometric profiles, prognoses, and potential syndromic features. Hereditary hearing loss can be syndromic or nonsyndromic, with nonsyndromic forms further classified by inheritance: autosomal-dominant or autosomal-recessive. In autosomal-dominant cases, three pathological mechanisms-haploinsufficiency, dominant-negative effects, and gain of function-are often implicated. Moreover, specific genes correlate with distinct audiometric patterns: WFS1 variants typically cause low-frequency hearing loss, whereas KCNQ4 and POU4F3 variants are linked to high-frequency loss. To investigate the underlying mechanisms of these frequency-dependent patterns, gene expression across cochlear turns was compared in mice, but interpretations of the results were limited because of inherent structural differences between rodent and primate cochleae. Therefore, the common marmoset (Callithrix jacchus), which offers closer anatomical and functional similarity to human cochleae, was utilized herein as an improved model. Using RNA sequencing (RNA-seq) across cochlear turns of common marmosets, the present study aimed to uncover gene expression and alternative splicing patterns that may explain tonotopic manifestations in hereditary hearing loss, including those caused by WFS1 variants, the present study being one such using common marmoset cochlear RNA-seq data, and these findings are highly valuable for genetic diagnosis and the development of gene therapies. - Source: PubMed
Publication date: 2026/02/07
Yokota ShuYoshimura HidekaneNishio Shin-YaSasaki ErikaMukasa KeisukeUsami Shin-IchiTakumi Yutaka - KCNQ4-encoded K7.4 voltage-gated potassium channels are expressed in hair-cells of the inner ear. Loss-of-function variants in KCNQ4 cause non-syndromic progressive hearing loss (DFNA2). K7.4 pore opening requires voltage-dependent conformational changes (activation) of the voltage-sensor domains (VSDs); however, how fast charge displacement during VSD activation is coupled to slow channel opening is currently unclear. Here, we optically tracked K7.4 VSD activation with voltage-clamp fluorometry, leveraging two fluorophores and pulsed excitation, and found that VSD activation comprises several voltage-dependent transitions, some with kinetics and voltage-dependence matching those of channel opening and closing. The DFNA2-causing R216H mutation impairs VSD movement and channel opening by destabilizing the active VSD configuration, a result confirmed by molecular dynamics simulations. We propose that the K7.4 VSD activates in two steps: a fast movement representing a first transition to an intermediate activation state, followed by slower component(s) that fully activate the VSD and drive channel opening. - Source: PubMed
Publication date: 2026/02/05
Nappi MarioFrampton Damon J AKusay Ali SWang KaiqianYasarbas S SuhedaPozzi SerenaMiceli FrancescoLiin Sara ITaglialatela MaurizioPantazis Antonios - The voltage-gated channel subfamily Q member 4 (KCNQ4), a K+ channel, is one of the most frequently mutated genes in autosomal dominant nonsyndromic hearing loss. KCNQ4, which contains 6 transmembrane domains and a long cytoplasmic C-terminal tail, plays a crucial role in K+ recycling in the inner ear. Although KCNQ4 binds to various interactors, specific binding sites of the interactors remain elusive, and the biological significance of these interactions remains unknown. Therefore, this study aimed to discover a novel interactor of KCNQ4 and delineate its functional role in KCNQ4 regulation. We discovered a novel interactor of KCNQ4, huntingtin-associated protein 1 (HAP1), in addition to calmodulin, which interacts with the C-terminus of KCNQ4 using a yeast 2-hybrid assay. This interaction requires the B-segment of KCNQ4 as demonstrated by protein domain analysis. A thorough investigation of the biochemical and physiological consequences of this association revealed that HAP1 overexpression reduced surface expression and attenuated the potassium current mediated by KCNQ4. This suggests that HAP1 acts as a negative regulator of KCNQ4, potentially through the disruption of normal endocytic trafficking. These findings enhance the understanding of KCNQ4 regulation at the molecular level and highlight the potential of the HAP1-KCNQ4 axis as a target for interventions aimed at maintaining channel surface stability. - Source: PubMed
Publication date: 2026/01/29
Kim Jung AhOh Kyung SeokRoh Jae WonKoh Young IkLin HaiyueJung JinseiGee Heon Yung - The KCNQ4 gene is closely associated with autosomal dominant nonsyndromic hearing loss (DFNA2) and encodes a potassium channel crucial for potassium ion circulation in the inner ear. This study identified a novel KCNQ4 variant, c.825G>T (p.Trp275Cys), associated with progressive hereditary hearing loss in a family. In vitro experiments and structural predictions revealed that this mutation did not affect KCNQ4 channel localization, subunit assembly, or pore size. However, the mutation induced longitudinal extension of the channel, reduced protein stability, and impaired potassium ion selectivity, thereby disrupting potassium ion homeostasis in the inner ear and ultimately leading to hearing loss. Zebrafish models further validated the critical role of the kcnq4 gene in inner ear development. We used morpholino to knock down kcnq4 in zebrafish and rescued the phenotype by reintroducing wild-type kcnq4 mRNA. This approach revealed significant changes in otolith morphology, a marked reduction in hair cell numbers, and abnormal motor responses. Additionally, we cloned and completed the coding sequence (CDS) of kcnq4 mRNA from the AB strain of zebrafish, enriching the available database information. Our findings provide new insights into the molecular mechanisms underlying KCNQ4-related hereditary hearing loss and lay the groundwork for developing precision treatments and early intervention strategies. - Source: PubMed
Jia HuiLiu XiaowenChen HuiWang YanliGuan Min-XinGuo Yufen