ArticleGenome medicine2018
Rare variants in SOX17 are associated with pulmonary arterial hypertension with congenital heart disease.
Article in Genome medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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Who cites it
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 158 citations in OpenAlex.
- Differential expression of members of SOX family of transcription factors in failing human hearts.Translational research : the journal of laboratory and clinical medicine · 2022Pooled it
- Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.The Lancet. Respiratory medicine · 2019Pooled it
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Cardiovascular Genetic Epidemiology in the Genome-Wide Era: From Association Discovery to Mechanistic Dissection and Clinical Translation.Cardiovascular drugs and therapy · 2026Review
- Broiler Ascites Syndrome as a Potential Spontaneous Animal Model for Human Pulmonary Arterial Hypertension: A Narrative Review.Life (Basel, Switzerland) · 2026Review
- Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial CaArteriosclerosis, thrombosis, and vascular biology · 2026Review
- Experimental pulmonary arterial hypertension in mice with a pathogenic SOX17 variant.Scientific reports · 2026Article
- Advances in the pathogenesis and clinical management of pulmonary hypertension.Medical review (2021) · 2026Review
- The Role of Genetics in Congenital Heart Disease-Associated Pulmonary Arterial Hypertension.Pediatric cardiology · 2026Observational
- A second-hit conceptual framework for pulmonary arterial hypertension in adult congenital heart disease: genetics, hemodynamics, and treat-and-repair.Frontiers in cardiovascular medicine · 2026Review
- Cardiometabolic disease and cardio-oncology: Insights from iPSC models and tissue engineering.Cell reports. Medicine · 2025Review
- The genetic epidemiology and genotype-phenotype correlations among Chinese children with idiopathic and heritable pulmonary arterial hypertension.Respiratory research · 2025Article
- SOX17 in pulmonary arterial hypertension: from development to clinical phenotype.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Common shunt lesions with pulmonary hypertension-who will benefit from surgery?Indian journal of thoracic and cardiovascular surgery · 2025Review
- Pathogenic SMAD6 variants in patients with idiopathic and complex congenital heart disease associated pulmonary arterial hypertension.NPJ genomic medicine · 2025Article
- Review
- 2025 Heart Disease and Stroke Statistics: A Report of US and Global Data From the American Heart Association.Circulation · 2025Review
- InvestigatingFrontiers in endocrinology · 2025Article
- Genetics and precision genomics approaches to pulmonary hypertension.The European respiratory journal · 2024Review
- Expanding the phenotype of PPP1R21-related neurodevelopmental disorder.Clinical genetics · 2024Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
Abstract
backgroundPulmonary arterial hypertension (PAH) is a rare disease characterized by distinctive changes in pulmonary arterioles that lead to progressive pulmonary arterial pressures, right-sided heart failure, and a high mortality rate. Up to 30% of adult and 75% of pediatric PAH cases are associated with congenital heart disease (PAH-CHD), and the underlying etiology is largely unknown. There are no known major risk genes for PAH-CHD.
methodsTo identify novel genetic causes of PAH-CHD, we performed whole exome sequencing in 256 PAH-CHD patients. We performed a case-control gene-based association test of rare deleterious variants using 7509 gnomAD whole genome sequencing population controls. We then screened a separate cohort of 413 idiopathic and familial PAH patients without CHD for rare deleterious variants in the top association gene.
resultsWe identified SOX17 as a novel candidate risk gene (p = 5.5e-7). SOX17 is highly constrained and encodes a transcription factor involved in Wnt/β-catenin and Notch signaling during development. We estimate that rare deleterious variants contribute to approximately 3.2% of PAH-CHD cases. The coding variants identified include likely gene-disrupting (LGD) and deleterious missense, with most of the missense variants occurring in a highly conserved HMG-box protein domain. We further observed an enrichment of rare deleterious variants in putative targets of SOX17, many of which are highly expressed in developing heart and pulmonary vasculature. In the cohort of PAH without CHD, rare deleterious variants of SOX17 were observed in 0.7% of cases.
conclusionsThese data strongly implicate SOX17 as a new risk gene contributing to PAH-CHD as well as idiopathic/familial PAH. Replication in other PAH cohorts and further characterization of the clinical phenotype will be important to confirm the precise role of SOX17 and better estimate the contribution of genes regulated by SOX17.
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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.