Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus

Sergey V. Kozyrev, Anna Karin Abelson, Jerome Wojcik, Ammar Zaghlool, M. V.Prasad Linga Reddy, Elena Sanchez, Iva Gunnarsson, Elisabet Svenungsson, Gunnar Sturfelt, Andreas Jönsen, Lennart Truedsson, Bernardo A. Pons-Estel, Torsten Witte, Sandra D'Alfonso, Nadia Barrizzone, Maria Giovanna Danieli, Carmen Gutierrez, Ana Suarez, Peter Junker, Helle LaustrupMaria Francisca González-Escribano, Javier Martin, Hadi Abderrahim, Marta E. Alarcón-Riquelme

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    342 Citations (Scopus)


    Systemic lupus erythematosus (SLE) is a prototypical autoimmune disease characterized by production of autoantibodies and complex genetic inheritance. In a genome-wide scan using 85,042 SNPs, we identified an association between SLE and a nonsynonymous substitution (rs10516487, R61H) in the B-cell scaffold protein with ankyrin repeats gene, BANK1. We replicated the association in four independent case-control sets (combined P = 3.7 × 10-10; OR = 1.38). We analyzed BANK1 cDNA and found two isoforms, one full-length and the other alternatively spliced and lacking exon 2 (Δ2), encoding a protein without a putative IP3R-binding domain. The transcripts were differentially expressed depending on a branch point-site SNP, rs17266594, in strong linkage disequilibrium (LD) with rs10516487. A third associated variant was found in the ankyrin domain (rs3733197, A383T). Our findings implicate BANK1 as a susceptibility gene for SLE, with variants affecting regulatory sites and key functional domains. The disease-associated variants could contribute to sustained B cell-receptor signaling and B-cell hyperactivity characteristic of this disease.

    Original languageEnglish
    Pages (from-to)211-216
    Number of pages6
    JournalNature Genetics
    Issue number2
    Publication statusPublished - 1 Feb 2008


    ASJC Scopus subject areas

    • Genetics

    Cite this

    Kozyrev, S. V., Abelson, A. K., Wojcik, J., Zaghlool, A., Linga Reddy, M. V. P., Sanchez, E., Gunnarsson, I., Svenungsson, E., Sturfelt, G., Jönsen, A., Truedsson, L., Pons-Estel, B. A., Witte, T., D'Alfonso, S., Barrizzone, N., Danieli, M. G., Gutierrez, C., Suarez, A., Junker, P., ... Alarcón-Riquelme, M. E. (2008). Functional variants in the B-cell gene BANK1 are associated with systemic lupus erythematosus. Nature Genetics, 40(2), 211-216.