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Human Disease Phenotypes Associated with Loss and Gain of Function Mutations in STAT2: Viral Susceptibility and Type I Interferonopathy

Lookup NU author(s): Dr Christopher DuncanORCiD, Professor Sophie HambletonORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


STAT2 is distinguished from other STAT family members by its exclusive involvement in type I and III interferon (IFN-I/III) signaling pathways, and its unique behavior as both positive and negative regulator of IFN-I signaling. The clinical relevance of these opposing STAT2 functions is exemplified by monogenic diseases of STAT2. Autosomal recessive STAT2 deficiency results in heightened susceptibility to severe and/or recurrent viral disease, whereas homozygous missense substitution of the STAT2-R148 residue is associated with severe type I interferonopathy due to loss of STAT2 negative regulation. Here we review the clinical presentation, pathogenesis, and management of these disorders of STAT2.

Publication metadata

Author(s): Duncan CJA, Hambleton S

Publication type: Review

Publication status: Published

Journal: Journal of Clinical Immunology

Year: 2021

Volume: 41

Issue: 7

Pages: 1446-1456

Print publication date: 06/10/2021

Online publication date: 26/08/2021

Acceptance date: 03/08/2021

ISSN (print): 0271-9142

ISSN (electronic): 1573-2592


DOI: 10.1007/s10875-021-01118-z

PubMed id: 34448086