The Myeloma Risk Variant of TNFRSF13B Shows Reduced NF ‐ κB

ABSTRACT

A single nucleotide variant rs34562254 in TNFRSF13B , which encodes TACI (transmembrane activator and CAML interactor), is associated with an increased risk of myeloma and MGUS. This variant encodes a proline to leucine substitution at residue 251 in the long isoform (P251L) and residue 205 in the short isoform (P205L) of TACI. Using HEK293 cells, NF‐κB signalling of the variant and wild type forms of TACI was measured by using an NF‐κB‐luciferase reporter assay and by quantifying NF‐κB p65 subcellular localisation. The TACI P205L variant showed substantially reduced NF‐κB activity compared to the wild type version of the short isoform. This result suggests an indirect effect of TACI P205L on the increased risk of myeloma.