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 Barizzone, Nadia Barrizzone, Maria Giovanna Danieli, Carmen Gutierrez, Ana Suarez, Peter JunkerHelle Laustrup, Maria Francisca González-Escribano, Javier Martin, Hadi Abderrahim, Marta E Alarcón-Riquelme

Research output: Contribution to journalJournal articleResearchpeer-review


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 x 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 (Delta2), 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
JournalNature Genetics
Issue number2
Pages (from-to)211-216
Number of pages5
Publication statusPublished - 1. Feb 2008


  • Adaptor Proteins, Signal Transducing
  • Alleles
  • Alternative Splicing
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Amino Acid Substitution
  • Ankyrin Repeat
  • B-Lymphocytes
  • Case-Control Studies
  • Chromosomes, Human
  • Cohort Studies
  • DNA, Complementary
  • Exons
  • Gene Deletion
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genome, Human
  • Haplotypes
  • Histidine
  • Humans
  • Introns
  • Linkage Disequilibrium
  • Logistic Models
  • Lupus Erythematosus, Systemic
  • Membrane Proteins
  • Molecular Sequence Data
  • Physical Chromosome Mapping
  • Polymorphism, Single Nucleotide
  • Protein Isoforms
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA
  • Sweden
  • Variation (Genetics)


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