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

The Italian Collaborative Group

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)569-579
Number of pages11
JournalHuman molecular genetics
Volume18
Issue number3
DOIs
StatePublished - Nov 3 2008

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ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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