ArticleNature medicine2021
PPIL4 is essential for brain angiogenesis and implicated in intracranial aneurysms in humans.
Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Gene therapy for intracranial aneurysms: systemic review.Journal of neurointerventional surgery · 2025Pooled it
- A systematic review and meta-analysis of Comaneci/Cascade temporary neck bridging devices for the treatment of intracranial aneurysms.Frontiers in human neuroscience · 2023Pooled it
- Review
- The Role of Furin in Hallmarks of Aneurysms: A Focus On Its Substrates.Current atherosclerosis reports · 2026Review
- Genomic and transcriptomic analyses revealed potential candidate genes for egg production traits in domesticated ducks.Poultry science · 2026Article
- Human Cyclophilins-An Emerging Class of Drug Targets.Medicinal research reviews · 2026Review
- Small extracellular vesicles produced by homeostatic phenotype BMSC promote bone regeneration by transferring anti-senescent factor JMJD6.Journal of nanobiotechnology · 2026Article
- Rare genetic variants inInternational journal of stroke : official journal of the International Stroke Society · 2025Article
- Unveiling the hidden interactome of CRBN molecular glues.Nature communications · 2025Article
- Direct blood flow velocity measurements of zebrafish cerebral vessels with a dual-mode light-sheet microscope.Biomedical optics express · 2025Article
- Article
- Review
- Kisspeptin-10 Prevents the Development of Cerebral Aneurysms by Reducing the Expression of Egr-1.CNS neuroscience & therapeutics · 2025Article
- Modeling thoracic aortic genetic variants in the zebrafish: useful for predicting clinical pathogenicity?Frontiers in cardiovascular medicine · 2025Review
- MicroRNA-451 Regulates Angiogenesis in Intracerebral Hemorrhage by Targeting Macrophage Migration Inhibitory Factor.Molecular neurobiology · 2024Article
- Systematic identification of post-transcriptional regulatory modules.Nature communications · 2024Article
- Neural Regulation of Vascular Development: Molecular Mechanisms and Interactions.Biomolecules · 2024Review
- Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis.eLife · 2024Article
- Hemodynamics regulate spatiotemporal artery muscularization in the developing circle of Willis.bioRxiv : the preprint server for biology · 2024Article
- Serum Interleukin-1 Levels Are Associated with Intracranial Aneurysm Instability.Translational stroke research · 2024Article
Corrections and comments
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Authors and funding
40 authors at 6 institutions in 2 countries.
Funding
Abstract
Intracranial aneurysm (IA) rupture leads to subarachnoid hemorrhage, a sudden-onset disease that often causes death or severe disability. Although genome-wide association studies have identified common genetic variants that increase IA risk moderately, the contribution of variants with large effect remains poorly defined. Using whole-exome sequencing, we identified significant enrichment of rare, deleterious mutations in PPIL4, encoding peptidyl-prolyl cis-trans isomerase-like 4, in both familial and index IA cases. Ppil4 depletion in vertebrate models causes intracerebral hemorrhage, defects in cerebrovascular morphology and impaired Wnt signaling. Wild-type, but not IA-mutant, PPIL4 potentiates Wnt signaling by binding JMJD6, a known angiogenesis regulator and Wnt activator. These findings identify a novel PPIL4-dependent Wnt signaling mechanism involved in brain-specific angiogenesis and maintenance of cerebrovascular integrity and implicate PPIL4 gene mutations in the pathogenesis of IA.
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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.