ArticleCirculation2019
Defects in the Exocyst-Cilia Machinery Cause Bicuspid Aortic Valve Disease and Aortic Stenosis.
Article in Circulation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Mendelian pathway analysis of laboratory traits reveals distinct roles for ciliary subcompartments in common disease pathogenesis.American journal of human genetics · 2021Pooled it
- Deletion of exocyst component 5 suppresses repair of injured kidney by limiting cell proliferation.Cell death discovery · 2026Article
- Deficiency of exocyst complex component Exoc5 exacerbates the progression of kidney fibrosis.Experimental & molecular medicine · 2026Article
- Broadening horizons: new links between cilia and heart development and disease.Frontiers in cardiovascular medicine · 2026Review
- The exocyst in ciliogenesis.Renal failure · 2025Review
- Remodelling of supernumerary leaflet primordia leads to bicuspid aortic valve caused by loss of primary cilia.Cardiovascular research · 2025Article
- Age Differences in Aortic Stenosis.Reviews in cardiovascular medicine · 2025Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- A tale of Rabs and the exocyst complex in ciliary trafficking and biogenesis.Frontiers in cell and developmental biology · 2025Review
- Unraveling the Mechanisms of Valvular Heart Disease to Identify Medical Therapy Targets: A Scientific Statement From the American Heart Association.Circulation · 2024Review
- Oocyte-specific EXOC5 expression is required for mouse oogenesis and folliculogenesis.Molecular human reproduction · 2024Article
- Insights into the Inherited Basis of Valvular Heart Disease.Current cardiology reports · 2024Review
- 2024 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2024Review
- Matrisome and Immune Pathways Contribute to Extreme Vascular Outcomes in Williams-Beuren Syndrome.Journal of the American Heart Association · 2024Article
- Functions of cilia in cardiac development and disease.Annals of human genetics · 2024Review
- CRELD1 variants are associated with bicuspid aortic valve in Turner syndrome.Human genetics · 2023Article
- Heart Disease and Stroke Statistics-2023 Update: A Report From the American Heart Association.Circulation · 2023Review
- Congenital aortic valve stenosis: from pathophysiology to molecular genetics and the need for novel therapeutics.Frontiers in cardiovascular medicine · 2023Review
- Primary cilia-associated protein IFT172 in ciliopathies.Frontiers in cell and developmental biology · 2023Review
- Patients with Bicuspid Aortopathy and Aortic Dilatation.Journal of clinical medicine · 2022Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundBicuspid aortic valve (BAV) disease is a congenital defect that affects 0.5% to 1.2% of the population and is associated with comorbidities including ascending aortic dilation and calcific aortic valve stenosis. To date, although a few causal genes have been identified, the genetic basis for the vast majority of BAV cases remains unknown, likely pointing to complex genetic heterogeneity underlying this phenotype. Identifying genetic pathways versus individual gene variants may provide an avenue for uncovering additional BAV causes and consequent comorbidities.
methodsWe performed genome-wide association Discovery and Replication Studies using cohorts of 2131 patients with BAV and 2728 control patients, respectively, which identified primary cilia genes as associated with the BAV phenotype. Genome-wide association study hits were prioritized based on
resultsGenome-wide association study hits revealed an association between BAV and genetic variation in human primary cilia. The most associated single-nucleotide polymorphisms were identified in or near genes that are important in regulating ciliogenesis through the exocyst, a shuttling complex that chaperones cilia cargo to the membrane. Genetic dismantling of the exocyst resulted in impaired ciliogenesis, disrupted ciliogenic signaling and a spectrum of cardiac defects in zebrafish, and aortic valve defects including BAV, valvular stenosis, and valvular calcification in murine models.
conclusionsThese data support the exocyst as required for normal ciliogenesis during aortic valve morphogenesis and implicate disruption of ciliogenesis and its downstream pathways as contributory to BAV and associated comorbidities in humans.
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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.