biostudies-literatureUnknown25(2)Meesilpavikkai KThe STAT3 is an important regulator in a wide range of different cell types. Human <i>STAT3</i> variants are associated with several immune dysregulation diseases. The current study investigated the clinical, genetic, and immunobiological data obtained from a family with novel heterozygous <i>STAT3</i> variants located at p.Y360C of the DNA binding domain. The clinical manifestations of these patients include autoimmunity, immunodeficiency, and postnatal growth defects. Broad STAT3 regulated cells including patient primary immune cells and HEK293 cells harboring the variant were assessed. Remarkably high levels of STAT3-regulated cytokines were detected in the sera of the patients. STAT3 nuclear binding and STAT3 activity were higher in STAT3-transduced HEK293 cells containing the p.Y360C Immune networke18https://www.ebi.ac.uk/biostudies/studies/S-EPMC12056293biostudies-literatureNovel <i>STAT3</i> Y360C Gain-of-function Variant Underlies Immune Dysregulation and Aberrancy in Mitochondrial Dynamics.PMC12056293Martin van Hagen PMilanese CMastroberardino PGDik WADalm VASHBakker Mvan der Spek PJKaikaew KZhou ZIJspeert HVasic PHirankarn NSchrijver BMeesilpavikkai Kde Bie MSuratannon NSwagemakers SMASchliehe CKaiser FMPfalseNovel <i>STAT3</i> Y360C Gain-of-function Variant Underlies Immune Dysregulation and Aberrancy in Mitochondrial Dynamics.The STAT3 is an important regulator in a wide range of different cell types. Human <i>STAT3</i> variants are associated with several immune dysregulation diseases. The current study investigated the clinical, genetic, and immunobiological data obtained from a family with novel heterozygous <i>STAT3</i> variants located at p.Y360C of the DNA binding domain. The clinical manifestations of these patients include autoimmunity, immunodeficiency, and postnatal growth defects. Broad STAT3 regulated cells including patient primary immune cells and HEK293 cells harboring the variant were assessed. Remarkably high levels of STAT3-regulated cytokines were detected in the sera of the patients. STAT3 nuclear binding and STAT3 activity were higher in STAT3-transduced HEK293 cells containing the p.Y360C 2025-01-01T00:00:00Z2025 Apr2026-04-18T03:22:17.351Z2026-04-18T03:11:58.947ZS-EPMC120562934034284410.4110/in.2025.25.e18