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While mutations in the bone morphogenetic protein receptor type II (BMPR2) gene are the single most common causal factor for hereditary cases, pathogenic mutations have been observed in approximately 25% of idiopathic PAH patients without a prior family history of disease. Additional defects of the transforming growth factor beta pathway have been implicated in disease pathogenesis. Specifically, studies have confirmed activin A receptor type II-like 1 (ACVRL1), endoglin (ENG), and members of the SMAD family as contributing to PAH both with and without associated clinical phenotypes. Most recently, next-generation sequencing has identified novel, rare genetic variation implicated in the PAH disease spectrum. Of importance, several identified genetic factors converge on related pathways and provide significant insight into the development, maintenance, and pathogenetic transformation of the pulmonary vascular bed. Together, these analyses represent the largest comprehensive compilation of BMPR2 and associated genetic risk factors for PAH, comprising known and novel variation. Additionally, with the inclusion of an allelic series of locus-specific variation in BMPR2, these data provide a key resource in data interpretation and development of contemporary therapeutic and diagnostic tools.","is_dataset_classified":null,"base_score":5.44673737166631,"endowment":5.44673737166631,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"26387786","pmcid":"PMC4822159","openalex_id":"https://openalex.org/W1824340961","authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"G0800784","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"P30 DK026687","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL060056","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/K020919/1","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"R01 HL098199","title":null},{"funder_name":"British Heart Foundation","grant_id":"RG/13/4/30107","title":null},{"funder_name":"National Institute for Health Research (NIHR)","grant_id":"NF-SI-0514-10086","title":null},{"funder_name":"Medical Research Council","grant_id":"G1000847","title":null},{"funder_name":"NHLBI NIH HHS","grant_id":"P01 HL108800","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R01HL060056-07","title":"Genetic Aspects of Pulmonary Hypertension"},{"funder_name":"National Institutes of Health","grant_id":"7R01HL098199-07","title":"Germline and Somatic Genetic Changes in Pulmonary Arterial Hypertension"}],"total_grants":11,"fwci":19.0357,"citation_percentile":0.99557354,"influential_citations":0,"citation_trend":[{"year":2015,"count":2},{"year":2016,"count":30},{"year":2017,"count":26},{"year":2018,"count":29},{"year":2019,"count":18},{"year":2020,"count":30},{"year":2021,"count":22},{"year":2022,"count":26},{"year":2023,"count":18},{"year":2024,"count":19},{"year":2025,"count":8},{"year":2026,"count":3}],"oa_status":"green","license":"cc-by","oa_locations":[{"url":"https://figshare.com/articles/journal_contribution/Pulmonary_arterial_hypertension_a_current_perspective_on_established_and_emerging_molecular_genetic_defects/24344614","host_type":"repository"},{"url":"https://figshare.com/articles/journal_contribution/Pulmonary_arterial_hypertension_a_current_perspective_on_established_and_emerging_molecular_genetic_defects/24344614","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fhumu.22904","host_type":"publisher"},{"url":"http://onlinelibrary.wiley.com/wol1/doi/10.1002/humu.22904/fullpdf","host_type":"publisher"},{"url":"https://doi.org/10.1002/humu.22904","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/26387786","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4822159","host_type":"repository"},{"url":"http://qmro.qmul.ac.uk/xmlui/handle/123456789/12476","host_type":"repository"},{"url":"http://eprints.lincoln.ac.uk/id/eprint/19642/1/humu22904.pdf","host_type":""},{"url":"https://openaccess.sgul.ac.uk/id/eprint/110211/1/nihms760153.pdf","host_type":""},{"url":"https://dx.doi.org/10.1002/humu.22904","host_type":""},{"url":"https://hdl.handle.net/10779/lincoln.24344614.v4","host_type":""},{"url":"https://figshare.com/articles/Pulmonary_arterial_hypertension_a_current_perspective_on_established_and_emerging_molecular_genetic_defects/24344614/4","host_type":""},{"url":"https://doi.org/https://doi.org/10.1002/humu.22904","host_type":""}],"fields_of_study":["Pulmonary Hypertension Research and Treatments","Bone health and treatments","Medical Imaging and Pathology Studies","0301 basic medicine","03 medical and health sciences","0303 health sciences","Animals","Bone Morphogenetic Protein Receptors, Type II","Disease Models, Animal","Genetic Association Studies","Genetic Counseling","Genetic Predisposition to Disease","Genetic Variation","High-Throughput Nucleotide Sequencing","Humans","Hypertension, Pulmonary","Multigene Family","Mutation","Signal Transduction","Transforming Growth Factor beta"],"mesh_terms":["Animals","Disease Models, Animal","Multigene Family","Genetic Counseling","Humans","Hypertension, Pulmonary","Mutation","Genetic Variation","Signal Transduction","Transforming Growth Factor beta","Genetic Predisposition to Disease","Bone Morphogenetic Protein Receptors, Type II","Genetic Association Studies","High-Throughput Nucleotide Sequencing"],"keywords":["BMPR2","ACVRL1","Biology","Endoglin","Genetics","Bioinformatics","Disease","Pulmonary hypertension","Allele","Locus (genetics)","Phenotype","Genetic variation","Pathogenesis","SMAD","Bone morphogenetic protein","Gene","Immunology","Pathology","Internal medicine","Medicine","Smad4","Smad1","Haploinsufficiency","Eng","Cav1","Kcna5","Locus Heterogeneity","Smad9","Eif2ak4","Kcnk3","Hypertension, Pulmonary","610","Genetic Counseling","Pulmonary arterial hypertension","C431 - 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