ArticleEMBO molecular medicine2020
Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 27 citations in OpenAlex.
- Structural mechanism for noncanonical GPCR signaling in the Hedgehog pathway.Nature structural & molecular biology · 2026Article
- Ciliary-Mediated Mechanotransduction in Skeletal Development and Diseases.Results and problems in cell differentiation · 2026Review
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Genome-Based Advances in Modeling Renal Ciliopathies and Enhancing Patient Care.Kidney & blood pressure research · 2025Review
- GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.PLoS biology · 2024Article
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- Skeletal ciliopathy: pathogenesis and related signaling pathways.Molecular and cellular biochemistry · 2024Review
- Reanalysis of Whole-Exome Sequencing Data of an Infant with Suspected Diagnosis of Jeune Syndrome Revealed a Likely Pathogenic Variant inMolecular syndromology · 2024Article
- GRK2 inhibits Flt-1Acta pharmaceutica Sinica. B · 2024Article
- Recent advances in primary cilia in bone metabolism.Frontiers in endocrinology · 2023Review
- Novel large deletion involving EVC and EVC2 in Ellis-van Creveld syndrome.Human genome variation · 2022Article
- Skeletal diseases caused by mutations inFrontiers in cell and developmental biology · 2022Article
- Research progress on the hedgehog signalling pathway in regulating bone formation and homeostasis.Cell proliferation · 2022Review
- SAG therapy restores bone growth and reduces enchondroma incidence in a model of skeletal chondrodysplasias caused by Ihh deficiency.Molecular therapy. Methods & clinical development · 2021Article
- G Protein-Coupled Receptor Kinase 2 as Novel Therapeutic Target in Fibrotic Diseases.Frontiers in immunology · 2021Review
- The Primary Cilium on Cells of Developing Skeletal Rudiments; Distribution, Characteristics and Response to Mechanical Stimulation.Frontiers in cell and developmental biology · 2021Article
- Differential Regulation of GPCRs-Are GRK Expression Levels the Key?Frontiers in cell and developmental biology · 2021Review
- Mutations in GRK2 cause Jeune syndrome by impairing Hedgehog and canonical Wnt signaling.EMBO molecular medicine · 2020Article
Corrections and comments
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Authors and funding
25 authors at 8 institutions in 2 countries.
Funding
Abstract
Mutations in genes affecting primary cilia cause ciliopathies, a diverse group of disorders often affecting skeletal development. This includes Jeune syndrome or asphyxiating thoracic dystrophy (ATD), an autosomal recessive skeletal disorder. Unraveling the responsible molecular pathology helps illuminate mechanisms responsible for functional primary cilia. We identified two families with ATD caused by loss-of-function mutations in the gene encoding adrenergic receptor kinase 1 (ADRBK1 or GRK2). GRK2 cells from an affected individual homozygous for the p.R158* mutation resulted in loss of GRK2, and disrupted chondrocyte growth and differentiation in the cartilage growth plate. GRK2 null cells displayed normal cilia morphology, yet loss of GRK2 compromised cilia-based signaling of Hedgehog (Hh) pathway. Canonical Wnt signaling was also impaired, manifested as a failure to respond to Wnt ligand due to impaired phosphorylation of the Wnt co-receptor LRP6. We have identified GRK2 as an essential regulator of skeletogenesis and demonstrate how both Hh and Wnt signaling mechanistically contribute to skeletal ciliopathies.
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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.