Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus. Academic Article uri icon

Overview

abstract

  • Systemic lupus erythematosus (SLE) is the prototypic systemic autoimmune disease. It is thought that many common variant gene loci of weak effect act additively to predispose to common autoimmune diseases, while the contribution of rare variants remains unclear. Here we describe that rare coding variants in lupus-risk genes are present in most SLE patients and healthy controls. We demonstrate the functional consequences of rare and low frequency missense variants in the interacting proteins BLK and BANK1, which are present alone, or in combination, in a substantial proportion of lupus patients. The rare variants found in patients, but not those found exclusively in controls, impair suppression of IRF5 and type-I IFN in human B cell lines and increase pathogenic lymphocytes in lupus-prone mice. Thus, rare gene variants are common in SLE and likely contribute to genetic risk.

authors

publication date

  • May 17, 2019

Research

keywords

  • Adaptor Proteins, Signal Transducing
  • Genetic Predisposition to Disease
  • Lupus Erythematosus, Systemic
  • Membrane Proteins
  • src-Family Kinases

Identity

PubMed Central ID

  • PMC6525203

Scopus Document Identifier

  • 85065811288

Digital Object Identifier (DOI)

  • 10.1038/nmeth.2089

PubMed ID

  • 31101814

Additional Document Info

volume

  • 10

issue

  • 1