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Gain-of-function variants in SYK cause immune...
Journal article

Gain-of-function variants in SYK cause immune dysregulation and systemic inflammation in humans and mice

Abstract

Spleen tyrosine kinase (SYK) is a critical immune signaling molecule and therapeutic target. We identified damaging monoallelic SYK variants in six patients with immune deficiency, multi-organ inflammatory disease such as colitis, arthritis and dermatitis, and diffuse large B cell lymphomas. The SYK variants increased phosphorylation and enhanced downstream signaling, indicating gain of function. A knock-in (SYK-Ser544Tyr) mouse model of a …

Authors

Wang L; Aschenbrenner D; Zeng Z; Cao X; Mayr D; Mehta M; Capitani M; Warner N; Pan J; Wang L

Journal

Nature Genetics, Vol. 53, No. 4, pp. 500–510

Publisher

Springer Nature

Publication Date

4 2021

DOI

10.1038/s41588-021-00803-4

ISSN

1061-4036