Activating germline mutations in STAT3 cause early-onset multi-organ autoimmune disease

Nat Genet. 2014 Aug;46(8):812-814. doi: 10.1038/ng.3040. Epub 2014 Jul 20.


Monogenic causes of autoimmunity provide key insights into the complex regulation of the immune system. We report a new monogenic cause of autoimmunity resulting from de novo germline activating STAT3 mutations in five individuals with a spectrum of early-onset autoimmune disease, including type 1 diabetes. These findings emphasize the critical role of STAT3 in autoimmune disease and contrast with the germline inactivating STAT3 mutations that result in hyper IgE syndrome.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autoimmune Diseases / genetics*
  • Cell Line
  • Genetic Predisposition to Disease
  • Germ-Line Mutation*
  • HEK293 Cells
  • Humans
  • Job Syndrome / genetics
  • Molecular Sequence Data
  • STAT3 Transcription Factor / genetics*
  • Sequence Homology, Amino Acid


  • STAT3 Transcription Factor
  • STAT3 protein, human