ArticleAmerican journal of human genetics2020
Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 64 citations in OpenAlex.
- Pathogenesis and precision management of osteogenesis imperfecta: from genetic mechanisms to novel therapies.World journal of pediatrics : WJP · 2026Review
- A regulatory circuit operated by KDELR1 and KDELR3 fine-tunes the composition of the early secretory pathway.Cellular and molecular life sciences : CMLS · 2026Article
- Molecular drivers of osteogenesis imperfecta: a cellular and extracellular collagen disease.Clinical science (London, England : 1979) · 2025Review
- Pediatric Scoliosis in Osteogenesis Imperfecta: From Genetic Mechanisms to Therapeutic Strategies.Orthopaedic surgery · 2025Review
- Splice‑site variant c.3531+1G>T inMolecular medicine reports · 2025Article
- Osteogenesis imperfecta: pathogenesis, classification, and treatment.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2025Review
- Example of Intrafamilial Clinical Polymorphism in a Family with Osteogenesis Imperfecta.Genes · 2025Article
- Genetic landscape and phenotypic spectrum of osteogenesis imperfecta in the Kazakhstani pediatric population.Scientific reports · 2025Article
- The role of heat shock proteins in fracture healing-a narrative review.European journal of trauma and emergency surgery : official publication of the European Trauma Society · 2025Review
- Comprehensive Review of Osteogenesis Imperfecta: Current Treatments and Future Innovations.Human gene therapy · 2025Review
- Bone Quality and Mineralization and Effects of Treatment in Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Update on the Genetics of Osteogenesis Imperfecta.Calcified tissue international · 2024Review
- Non-genetic diagnostic investigations in monogenic Ehlers-Danlos syndromes.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2024Article
- Genetic basis of osteogenesis imperfecta from a single tertiary centre in South Africa.European journal of human genetics : EJHG · 2024Article
- HSP47 in human diseases: Navigating pathophysiology, diagnosis and therapy.Clinical and translational medicine · 2024Review
- Osteogenesis imperfecta type 10 and the cellular scaffolds underlying common immunological diseases.Genes and immunity · 2024Review
- KDELR2 promotes bone marrow mesenchymal stem cell osteogenic differentiation via GSK3β/β-catenin signaling pathway.Cell and tissue research · 2024Article
- Article
- Emerging Landscape of Osteogenesis Imperfecta Pathogenesis and Therapeutic Approaches.ACS pharmacology & translational science · 2024Review
- Genomic prediction and genome-wide association studies of morphological traits and distraction index in Korean Sapsaree dogs.PloS one · 2024Article
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Authors and funding
38 authors at 14 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteogenesis imperfecta (OI) is characterized primarily by susceptibility to fractures with or without bone deformation. OI is genetically heterogeneous: over 20 genetic causes are recognized. We identified bi-allelic pathogenic KDELR2 variants as a cause of OI in four families. KDELR2 encodes KDEL endoplasmic reticulum protein retention receptor 2, which recycles ER-resident proteins with a KDEL-like peptide from the cis-Golgi to the ER through COPI retrograde transport. Analysis of patient primary fibroblasts showed intracellular decrease of HSP47 and FKBP65 along with reduced procollagen type I in culture media. Electron microscopy identified an abnormal quality of secreted collagen fibrils with increased amount of HSP47 bound to monomeric and multimeric collagen molecules. Mapping the identified KDELR2 variants onto the crystal structure of G. gallus KDELR2 indicated that these lead to an inactive receptor resulting in impaired KDELR2-mediated Golgi-ER transport. Therefore, in KDELR2-deficient individuals, OI most likely occurs because of the inability of HSP47 to bind KDELR2 and dissociate from collagen type I. Instead, HSP47 remains bound to collagen molecules extracellularly, disrupting fiber formation. This highlights the importance of intracellular recycling of ER-resident molecular chaperones for collagen type I and bone metabolism and a crucial role of HSP47 in the KDELR2-associated pathogenic mechanism leading to OI.
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