ArticleNature genetics2008
Gain-of-function mutations in TRPV4 cause autosomal dominant brachyolmia.
Article in Nature genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 231 citations in OpenAlex.
- 25+ Years of TRPV4: From Discovery to Translational Horizons.Research square · 2026Article
- Clinical, electrophysiological, and neuroimaging characterization of childhood-onset non-5q spinal muscular atrophies: a retrospective pediatric case series.Neurogenetics · 2026Article
- Expanding the Genotype and Phenotype Diversity in a Chinese Cohort With TRPV4-Related Dysplasia.Clinical genetics · 2026Article
- Small molecule inhibition rescues the skeletal dysplasia phenotype of Trpv4 mutant mice.JCI insight · 2026Article
- The Clinical Utility of Whole-Exome Sequencing in the Prenatal Diagnosis of Fetal Skeletal Dysplasia.International journal of women's health · 2026Article
- Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026Review
- A novel TRPV4 variant in spondylometaphyseal dysplasia, kozlowski type reveals a previously unreported loss-of-function mechanism.Orphanet journal of rare diseases · 2025Article
- Physiological functions and pharmacological targeting of transient receptor potential channels.Pharmacological reviews · 2025Review
- Moderately severe osteogenesis imperfecta-like osteochondrodysplasia associated with heterozygous variants in bothJBMR plus · 2025Article
- Skeletal dysplasia-causing mutations in TRPV4 alter the chondrocyte transcriptomic response to mechanical loading.American journal of physiology. Cell physiology · 2025Article
- TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential.Molecular neurobiology · 2025Review
- Comparison of the natural course of clinical and radiologic features in 13 patients with TRPV4-related skeletal dysplasias.Pediatric radiology · 2025Article
- Combined clinical, structural and cellular studies discriminate pathogenic and benign TRPV4 variants.Brain : a journal of neurology · 2025Article
- Tuning the Response of Synthetic Mechanogenetic Gene Circuits Using Mutations in TRPV4.Tissue engineering. Part A · 2025Article
- TRPV4 neuromuscular disease registry highlights bulbar, skeletal and proximal limb manifestations.Brain : a journal of neurology · 2025Article
- A QUARTER CENTURY OF CALCIUM-PERMEABLE ION CHANNEL, TRPV4: PERSPECTIVES ON EXPRESSION AND FUNCTION IN ENDOTHELIAL CELLS-TIME TO TRANSLATE.Transactions of the American Clinical and Climatological Association · 2025Review
- Recent advances on the structure and the function relationships of the TRPV4 ion channel.Channels (Austin, Tex.) · 2024Review
- Identification and Properties of TRPV4 Mutant Channels Present in Polycystic Kidney Disease Patients.Function (Oxford, England) · 2024Article
- Compressive Myelopathy Secondary toJournal of pediatric genetics · 2024Article
- NovelGenes & diseases · 2024Article
68 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
The brachyolmias constitute a clinically and genetically heterogeneous group of skeletal dysplasias characterized by a short trunk, scoliosis and mild short stature. Here, we identify a locus for an autosomal dominant form of brachyolmia on chromosome 12q24.1-12q24.2. Among the genes in the genetic interval, we selected TRPV4, which encodes a calcium permeable cation channel of the transient receptor potential (TRP) vanilloid family, as a candidate gene because of its cartilage-selective gene expression pattern. In two families with the phenotype, we identified point mutations in TRPV4 that encoded R616Q and V620I substitutions, respectively. Patch clamp studies of transfected HEK cells showed that both mutations resulted in a dramatic gain of function characterized by increased constitutive activity and elevated channel activation by either mechano-stimulation or agonist stimulation by arachidonic acid or the TRPV4-specific agonist 4alpha-phorbol 12,13-didecanoate (4alphaPDD). This study thus defines a previously unknown mechanism, activation of a calcium-permeable TRP ion channel, in skeletal dysplasia pathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.