A loss-of-function variant of PTPN22 is associated with reduced risk of systemic lupus erythematosus

作者：Orru Valeria; Tsai Sophia J; Rueda Blanca; Fiorillo Edoardo; Stanford Stephanie M; Dasgupta Jhimli; Hartiala Jaana; Zhao Lei; Ortego Centeno Norberto; D'Alfonso Sandra; Arnett Frank C; Wu Hui; Gonzalez Gay Miguel A; Tsao Betty P; Pons Estel Bernardo; Alarcon Riquelme Marta E; He Yantao; Zhang Zhong Yin; Allayee Hooman; Chen Xiaojiang S; Martin Javier; Bottini Nunzio^*

来源：Human Molecular Genetics, 2009, 18(3): 569-579.

DOI：10.1093/hmg/ddn363

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, reinforcing the proposal that inhibition of LYP activity could be beneficial in human autoimmunity.

• 出版日期2009-2-1
• 单位河北医科大学