Protein informatics combined with multiple data sources enriches the clinical characterization of novel TRPV4 variant causing an intermediate skeletal dysplasia

摘要

BackgroundTransient receptor potential cation channel subfamily V member 4 (TRPV4) is an ion channel permeable to Ca²⁺ that is sensitive to physical, hormonal, and chemical stimuli. This protein is expressed in many cell types, including osteoclasts, chondrocytes, and sensory neurons. As such, pathogenic variants of this gene are associated with skeletal dysplasias and neuromuscular disorders. Pathogenesis of these phenotypes is not yet completely understood, but it is known that genotype–phenotype correlations for TRPV4 pathogenic variants often are not present.