Journal article

Functional rare and low frequency variants in BLK and BANK1 contribute to human lupus

Simon H Jiang, Vicki Athanasopoulos, Julia Ellyard, Aaron Chuah, Jean Cappello, Amelia Cook, Savit B Prabhu, Jacob Cardenas, Jinghua Gu, Maurice Stanley, Jonathan A Roco, Ilenia Papa, Mehmet Yabas, Giles D Walters, Gaetan Burgio, Kathryn McKeon, James M Byers, Charlotte Burrin, Anselm Enders, Lisa A Miosge Show all



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 suppressi..

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University of Melbourne Researchers


Funding Acknowledgements

Personnel of the Australian Cancer Research Foundation Biomolecular Resource Facility (JCSMR). Harpreet Vohra and Mick Devoy from the MCRF facility (JCSMR). Stuart Read and Nikki Ross from the Australian Phenomics Facility. FLAG-TRAF6 was a gift from Robert Brink and plasmids for BANK1 were a kind gift from Casamiro Castillejo-Lopez. RACP Jacquot NHMRC Award for Excellence, Jacquot Research Entry Scholarship, and NHMRC project grants to SHJ. NHMRC Program and project grants, and Elizabeth Blackburn Fellowship to CGV. This research/project was undertaken with the assistance of resources and services from the National Computational Infrastructure (NCI), which is supported by the Australian Government. This research and generation of CRISPR mice were also supported by funding of the Australian Government's National Collaborative Research Infrastructure Strategy to the Australian Phenomics Facility and Bioplatforms Australia. We acknowledge the MGRB Collaborative ( for granting us controlled access to the 45 and Up [1,2] and ASPREE [3] datasets as reference healthy controls.