A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus.
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ABSTRACT:
SUBMITTER: Orru V
PROVIDER: S-EPMC2722189 | biostudies-literature | 2009 Feb
REPOSITORIES: biostudies-literature
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A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus.
Orrú Valeria V Tsai Sophia J SJ Rueda Blanca B Fiorillo Edoardo E Stanford Stephanie M SM Dasgupta Jhimli J Hartiala Jaana J Zhao Lei L Ortego-Centeno Norberto N D'Alfonso Sandra S Arnett Frank C FC Wu Hui H Gonzalez-Gay Miguel A MA Tsao Betty P BP Pons-Estel Bernardo B Alarcon-Riquelme Marta E ME He Yantao Y Zhang Zhong-Yin ZY Allayee Hooman H Chen Xiaojiang S XS Martin Javier J Bottini Nunzio N
Human molecular genetics 20081103 3
A gain-of-function R620W polymorphism in the PTPN22 gene, encoding the lymphoid tyrosine phosphatase LYP, has recently emerged as an important risk factor for human autoimmunity. Here we report that another missense substitution (R263Q) within the catalytic domain of LYP leads to reduced phosphatase activity. High-resolution structural analysis revealed the molecular basis for this loss of function. Furthermore, the Q263 variant conferred protection against human systemic lupus erythematosus, re ...[more]
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