ArticlePloS one2015
Structural modeling of a novel CAPN5 mutation that causes uveitis and neovascular retinal detachment.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- Idiopathic unilateral ocular vasculitis in a young adult: a case report on clinical course and steroid response.Annals of medicine and surgery (2012) · 2026Article
- Article
- The Identification of Proteolytic Substrates of Calpain-5 with N-Terminomics.International journal of molecular sciences · 2025Article
- Treatment and Visual Outcomes in Pediatric Patients with Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy: A Cohort Study.Ocular immunology and inflammation · 2024Article
- Bilateral macular hole in a patient with CAPN5-related neovascular inflammatory vitreoretinopathy.Documenta ophthalmologica. Advances in ophthalmology · 2023Article
- Impaired activity and membrane association of most calpain-5 mutants causal for neovascular inflammatory vitreoretinopathy.Biochimica et biophysica acta. Molecular basis of disease · 2023Article
- Calpains as mechanistic drivers and therapeutic targets for ocular disease.Trends in molecular medicine · 2022Review
- Long-Term Outcomes and Risk Factors for Severe Vision Loss in Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy (ADNIV).American journal of ophthalmology · 2022Observational
- The C2 domain of calpain 5 contributes to enzyme activation and membrane localization.Biochimica et biophysica acta. Molecular cell research · 2021Article
- Whole-Exome Sequencing of Patients With Posterior Segment Uveitis.American journal of ophthalmology · 2021Article
- Molecular Surgery: Proteomics of a Rare Genetic Disease Gives Insight into Common Causes of Blindness.iScience · 2020Review
- Structural Insights into the Unique Activation Mechanisms of a Non-classical Calpain and Its Disease-Causing Variants.Cell reports · 2020Article
- CAPN5 genetic inactivation phenotype supports therapeutic inhibition trials.Human mutation · 2019Article
- Proteomic insight into the pathogenesis of CAPN5-vitreoretinopathy.Scientific reports · 2019Article
- VCAN Canonical Splice Site Mutation is Associated With Vitreoretinal Degeneration and Disrupts an MMP Proteolytic Site.Investigative ophthalmology & visual science · 2019Article
- Two Novel CAPN5 Variants Associated with Mild and Severe Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy Phenotypes.Ocular immunology and inflammation · 2019Article
- In Vivo Expression of Mutant Calpains in the Eye Using Lentivirus.Methods in molecular biology (Clifton, N.J.) · 2019Article
- Capn5 Expression in the Healthy and Regenerating Zebrafish Retina.Investigative ophthalmology & visual science · 2018Article
- A novel de novoCold Spring Harbor molecular case studies · 2018Article
- Gene Therapy Restores Mfrp and Corrects Axial Eye Length.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
CAPN5 mutations have been linked to autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV), a blinding autoimmune eye disease. Here, we link a new CAPN5 mutation to ADNIV and model the three-dimensional structure of the resulting mutant protein. In our study, a kindred with inflammatory vitreoretinopathy was evaluated by clinical eye examinations, DNA sequencing, and protein structural modeling to investigate the disease-causing mutation. Two daughters of an affected mother demonstrated symptoms of stage III ADNIV, with posterior uveitis, cystoid macular edema, intraocular fibrosis, retinal neovascularization, retinal degeneration, and cataract. The women also harbored a novel guanine to thymine (c.750G>T, p.Lys250Asn) missense mutation in exon 6 of CAPN5, a gene that encodes a calcium-activated cysteine protease, calpain-5. Modeling based on the structures of all known calpains revealed the mutation falls within a calcium-sensitive flexible gating loop that controls access to the catalytic groove. Three-dimensional modeling placed the new mutation in a region adjacent to two previously identified disease-causing mutations, all three of which likely disrupt hydrogen bonding within the gating loop, yielding a CAPN5 with altered enzymatic activity. This is the third case of a CAPN5 mutation leading to inherited uveitis and neovascular vitreoretinopathy, suggesting patients with ADNIV features should be tested for CAPN5 mutations. Structural modeling of novel variants can be used to support mechanistic consequences of the disease-causing variants.
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