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All four substitutions result in strikingly different phenotypes, ranging from somatic infantile myofibromatosis in p.Asn666Lys and ocular pterygium\u2013digital keloid dysplasia in p.Asn666Tyr to a severe form of Penttinen syndrome in p.Asn666Ser, while p.Asn666His is associated with a complex phenotype characterized by debilitating hand and foot contractures and facial coarseness. Here, we show that the p.Asn666Lys, p.Asn666Tyr, and p.Asn666His substitutions result in increased total PDGFR<jats:italic>\u03b2<\/jats:italic> phosphorylation at 32\u00b0C compared to 37\u00b0C. All four substitutions exhibit distinct activation patterns of specific PDGFR<jats:italic>\u03b2<\/jats:italic> tyrosine residues at both temperatures, indicating a unique activation of each variant. The temperature effect on downstream signaling is present across all substitutions, resulting in substitution\u2010specific downstream signaling at both 37\u00b0C and 32\u00b0C. This complex interplay of downstream signaling proteins could be important for the clinical manifestations of p.Asn666 <jats:italic>PDGFRB<\/jats:italic> variants. Furthermore, variant\u2010specific overactivation of tyrosine residues and downstream signaling at 32\u00b0C emphasize the importance of temperature as an environmental factor in the pathogenesis of this diverse group of disorders.<\/jats:p>","DOI":"10.1155\/humu\/6664372","type":"journal-article","created":{"date-parts":[[2025,4,22]],"date-time":"2025-04-22T13:35:18Z","timestamp":1745328918000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Temperature as a Key Modulator: Investigating Phosphorylation Patterns of p.Asn666 <i>PDGFRB<\/i> Variants and Their Role in Downstream 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