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The classic human FOP variant, ACVR1<jats:sup>R206H<\/jats:sup>, shows increased bone morphogenetic protein (BMP) signaling and activation by activins.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Here, we performed in vivo functional characterization of human ACVR1<jats:sup>R206H<\/jats:sup> and orthologous zebrafish Acvr1l<jats:sup>R203H<\/jats:sup> using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity. Our results showed that human ACVR1<jats:sup>R206H<\/jats:sup> and zebrafish Acvr1l<jats:sup>R203H<\/jats:sup> exhibit functional differences in early embryonic zebrafish, and that human ACVR1<jats:sup>R206H<\/jats:sup> retained its signaling activity in the absence of a ligand\u2010binding domain (LBD). We also showed, for the first time, that zebrafish Acvr2ba\/Acvr2bb receptors are required for human ACVR1<jats:sup>R206H<\/jats:sup> signaling in early embryonic zebrafish.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together, these data provide new insight into ACVR1<jats:sup>R206H<\/jats:sup> signaling pathways that may facilitate the design of new and effective therapies for FOP patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/dvdy.566","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T04:25:43Z","timestamp":1672979143000},"page":"605-628","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Functional comparison of human <scp>ACVR1<\/scp> and zebrafish Acvr1l <scp>FOP<\/scp>\u2010associated variants in embryonic 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