The Myeloma Risk Variant of TNFRSF13B Shows Reduced NF-κB Signalling Activity in HEK293 Cells.

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.