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However, the downstream signaling pathways by which G\u03b1q-R183Q impairs vascular function remain poorly defined. To address this, we generated human dermal endothelial cells lacking endogenous G\u03b1q and expressing the G\u03b1q-R183Q mutant. Next, using SILAC-based quantitative proteomics, we mapped the G\u03b1q-R183Q-induced endothelial phosphoproteome. These analyses identified aberrant activation of the Calcineurin\u2013NFAT\u2013DSCR1.4 signaling cascade as a key pathogenic feature. NFAT dysregulation and DSCR1 expression in endothelial cells were confirmed in patient-derived biopsies. Pharmacological inhibition of Calcineurin with tacrolimus partially normalized NFAT signaling in G\u03b1q-R183Q endothelial cells. Strikingly, genetic depletion of DSCR1 in G\u03b1q-R183Q cells fully restored Calcineurin\/NFAT signaling and enabled proper endothelial migration and angiogenic sprouting, highlighting DSCR1 as a critical effector of G\u03b1q-R183Q signaling in CMs. These findings reveal a druggable signaling circuit downstream of G\u03b1q-R183Q that may serve as a foundation for future therapies targeting\n                    <jats:italic>GNAQ<\/jats:italic>\n                    -driven vascular malformations, including Sturge-Weber syndrome.\n                  <\/jats:p>","DOI":"10.1007\/s10456-026-10029-9","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T09:52:24Z","timestamp":1770198744000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Calcineurin-NFAT-DSCR1.4 signaling as druggable axis in G\u03b1q-R183Q\u2013driven capillary malformations"],"prefix":"10.1007","volume":"29","author":[{"given":"Tong","family":"Xu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera","family":"Janssen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nathalie R.","family":"Reinhard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Sobrevals-Alcaraz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert M.","family":"van Es","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annett","family":"de Haan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julian","family":"de Swart","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"Wehrens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannah","family":"de Kraker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Wolkerstorfer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chantal M. 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