LTBR Gene - Lymphotoxin Beta Receptor: Function, Expression, and Disease Associations

The LTBR gene encodes the lymphotoxin beta receptor (LTβR), a member of the tumor necrosis factor receptor (TNFR) superfamily. LTβR is expressed on the surface of stromal cells, epithelial cells, and myeloid cells, and binds the heterotrimeric ligand lymphotoxin α1β2 (LTα1β2) as well as LIGHT (TNFSF14). Activation of LTβR triggers canonical and non-canonical NF-κB signaling pathways, playing a critical role in the development and organization of secondary lymphoid organs, maintenance of lymph node architecture, and regulation of immune responses. LTBR is also involved in inflammatory signaling, apoptosis, and cancer progression.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Non-canonical NF-κB signaling (Reactome: R-HSA-5676590)

• Lymphotoxin beta receptor signaling (Reactome: R-HSA-5668541)

• TNFR2 non-canonical NF-κB pathway (KEGG: hsa04064)

• Cytokine-cytokine receptor interaction (KEGG: hsa04060)

The lymphotoxin beta receptor (LTβR) is a 435-amino acid type I transmembrane protein with an extracellular domain containing four cysteine-rich repeats characteristic of the TNFR superfamily. The intracellular domain contains TRAF-binding motifs that recruit TRAF2, TRAF3, and TRAF5, leading to activation of both canonical and non-canonical NF-κB pathways. LTβR is essential for the formation of lymph nodes, Peyer's patches, and splenic organization. It also regulates chemokine expression, dendritic cell homeostasis, and antiviral immunity. Aberrant LTβR signaling is implicated in autoimmune diseases and cancer.