RT Journal Article SR Electronic T1 The pathophysiological role of novel pulmonary arterial hypertension gene SOX17 JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP 2004172 DO 10.1183/13993003.04172-2020 VO 58 IS 3 A1 Yukyee Wu A1 John Wharton A1 Rachel Walters A1 Eleni Vasilaki A1 Jurjan Aman A1 Lan Zhao A1 Martin R. Wilkins A1 Christopher J. Rhodes YR 2021 UL http://erj.ersjournals.com/content/58/3/2004172.abstract AB Pulmonary arterial hypertension (PAH) is a progressive disease predominantly targeting pre-capillary blood vessels. Adverse structural remodelling and increased pulmonary vascular resistance result in cardiac hypertrophy and ultimately failure of the right ventricle. Recent whole-genome and whole-exome sequencing studies have identified SOX17 as a novel risk gene in PAH, with a dominant mode of inheritance and incomplete penetrance. Rare deleterious variants in the gene and more common variants in upstream enhancer sites have both been associated with the disease, and a deficiency of SOX17 expression may predispose to PAH. This review aims to consolidate the evidence linking genetic variants in SOX17 to PAH, and explores the numerous targets and effects of the transcription factor, focusing on the pulmonary vasculature and the pathobiology of PAH.SOX17, a risk gene in PAH, manifests in vivo phenotypes and interacts with key signalling pathways and transcriptional targets in the pathobiology of PAH. Restoration of SOX17 gene expression and signalling may represent a new therapeutic strategy in PAH. https://bit.ly/37ldkIL