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

Richard Muyan Chen1, Jackie L Ludgate1, Robert J Weeks1

  • 1Department of Pathology and Molecular Medicine, University of Otago, Dunedin, New Zealand.

European Journal of Haematology
|August 4, 2026
PubMed

Insights

A genetic variant in TNFRSF13B, encoding TACI (transmembrane activator and CAML interactor), is linked to myeloma risk. The TACI P205L variant shows reduced NF-κB activity, suggesting an indirect role in disease development.

Area of Science:

  • Immunology
  • Genetics

Background:

  • A single nucleotide variant (rs34562254) in TNFRSF13B, encoding TACI, is associated with increased risk of myeloma and MGUS.
  • This variant results in a proline to leucine substitution at residue 251 (long isoform) or 205 (short isoform) of TACI.

Purpose of the Study:

  • To investigate the functional impact of the TACI P205L variant on NF-κB signaling.
  • To explore the potential indirect mechanism linking TACI P205L to myeloma risk.

Main Methods:

  • Utilized HEK293 cells for experiments.
  • Assessed NF-κB signaling using an NF-κB-luciferase reporter assay.
  • Quantified NF-κB p65 subcellular localization.

Main Results:

  • The TACI P205L variant exhibited significantly reduced NF-κB activity compared to the wild-type short isoform.
  • NF-κB p65 subcellular localization patterns may differ between variant and wild-type TACI.

Conclusions:

  • The reduced NF-κB activity associated with the TACI P205L variant suggests an indirect contribution to the increased risk of myeloma.
  • Further research is warranted to fully elucidate the role of TACI signaling in myeloma pathogenesis.
Keywords:
TNFRSF13BHEK293 cellsNF‐κBTACImyeloma

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