Ask about this productRelated genes to: Clcn5 antibody
- Gene:
- CLCN5 NIH gene
- Name:
- chloride voltage-gated channel 5
- Previous symbol:
- NPHL2, NPHL1
- Synonyms:
- DENTS, XLRH, hClC-K2, hCIC-K2, CLC5, XRN, ClC-5
- Chromosome:
- Xp11.23
- Locus Type:
- gene with protein product
- Date approved:
- 1994-01-28
- Date modifiied:
- 2016-02-04
Related products to: Clcn5 antibody
Related articles to: Clcn5 antibody
- Dent disease type 1 is an X-linked proximal tubulopathy caused by pathogenic variants in , which encodes the chloride/proton exchanger, ClC-5. Loss of ClC-5 function disrupts receptor-mediated endocytosis, resulting in low-molecular-weight proteinuria, hypercalciuria, nephrocalcinosis, nephrolithiasis, and progressive kidney failure. Although many variants have been reported, existing resources remain incomplete, inconsistent, or based on different reference sequences (RefSeqs), thereby hindering variant comparison and clinical interpretation. A comprehensive and uniformly annotated catalog is needed to improve diagnostic accuracy and estimates of Dent disease type 1 prevalence. - Source: PubMed
Publication date: 2026/03/10
Lyu PinYoo Kyung WhanChen ZhuoLu FangyuCogal AndreaHarris Peter CLieske John CLu Baisong - Dent disease is a hereditary kidney tubular disorder caused by pathogenic variants in either the CLCN5 (Dent disease 1) or OCRL1 (Dent disease 2) genes. As a rare genetic disorder, Dent disease often presents with variable clinical manifestations, leading to frequent misdiagnosis or underdiagnosis, especially in milder cases. Consequently, limited research has addressed the long-term clinical outcomes of Dent disease. - Source: PubMed
Publication date: 2026/04/18
Yang Eun MiAhn Yo HanKim Ji HyunSong Ji YeonCho Min HyunHan Kyoung HeePark Se JinKang Hee GyungCho HeeyeonCheong Hae Il - Dent disease 1, an X-linked recessive proximal tubulopathy most commonly caused by variants, often presents with heterogeneous and nonspecific phenotypes that hinder clinical diagnosis in the absence of molecular data. We investigated a Chinese kindred with suspected hereditary renal disease using whole-exome sequencing and comprehensive analyses and identified a novel frameshift variant in (NM_001127899: c.2359dupG/p.R788Afs*24). Segregation analysis showed the proband to be hemizygous, with his mother and daughter as heterozygous carriers. Pathogenicity prediction, domain mapping against published variants, and literature review indicate that this variant lies within a functionally critical, variant-hotspot region of the protein where truncating variants correlate with classic Dent disease 1 phenotypes. Molecular docking and structural modeling further predict destabilization of the H/Cl exchange transporter 5 (CLC-5) dimer and reduced adenosine triphosphate (ATP)/adenosine diphosphate (ADP) binding affinity attributable to the frameshift, providing mechanistic plausibility for impaired channel function. Collectively, genetic, bioinformatic, and structural evidence support the p.R788Afs24 mutant as a likely pathogenic allele underlying the proband's renal phenotype, expanding the variant spectrum of and underscoring the necessity of genetic testing for accurate diagnosis and management of Dent disease 1. - Source: PubMed
Publication date: 2026/04/06
Zhang Si-YuanHuang HaoYu Zi-JieFan Liang-LiangJin Jie-YuanWang QinXu HuiZhu LeiLiu Yu-Xing - Dent's disease, an X-linked recessive disorder predominantly affecting males, is characterized by nephrocalcinosis, nephrolithiasis, and a high risk of progression to end-stage renal disease. Dent's disease type 1, accounting for 60% of cases, caused by mutations in the CLCN5 gene encoding the chloride ion channel protein ClC-5, exhibits significant clinical heterogeneity and variability in disease progression. The lack of hotspot mutations poses challenges for genetic diagnosis and counselling, complicating the prediction of disease outcomes. This study systematically evaluated the functional and structural impacts of 181 CLCN5 missense mutations using computational tools, including PredictSNP, MAGPIE, and molecular dynamics simulations, to propose a robust method for improving genetic counselling and prognosis prediction. Our analysis identified mutations at the dimer interface and chloride selectivity filter as critical disruptors of ClC-5 function and stability. Notably, molecular dynamics simulations of L200R, P213L, and G512R mutations revealed that L200R significantly destabilized the protein structure. Clinical data from a multicentre cohort of Chinese patients with CLCN5 mutations corroborated our computational predictions, highlighting the essential role of helix O in ClC-5 function. By integrating bioinformatics analyses with clinical validation, this study provides molecular insights into Dent's disease heterogeneity and proposes a framework for enhancing genetic counselling and prognostic assessment for affected patients. - Source: PubMed
Wu ChengpengZhang YingChen ZipeiFu HaidongDu ZhiChen LiqunWang GuozhenMao JianhuaHu Lidan - Pathogenic variants in the CLCN5 gene encoding the chloride-hydrogen exchanger ClC-5 cause Dent's disease type 1, a genetic disorder of the endolysosomal pathway in the proximal tubules of the kidneys. A hallmark of this disease is the downregulation of the protein uptake receptor consisting of megalin, cubilin and amnionless, causing low-molecular-weight proteinuria. Why these receptors are downregulated is not fully understood. - Source: PubMed
Publication date: 2026/02/12
Christer SalómonMarelja ZvonimirDibra IndiraHauschild HannahBerquez MarineGandhi HetviShih Yung-HsinKeller SvenjaHelmstädter MartinSchell ChristophDevuyst OlivierSimons Matias