TNFRSF13C Gene: BAFF-R Function, Mutations, and Disease Associations | Biomedical Resource

TNFRSF13C encodes the B-cell activating factor receptor (BAFF-R), a type III transmembrane protein of the tumor necrosis factor receptor superfamily. BAFF-R is predominantly expressed on mature B cells and binds the cytokine BAFF (B-cell activating factor, TNFSF13B). This interaction is essential for B-cell survival, maturation, and immunoglobulin production. The receptor signals through the NF-κB pathway via TRAF3 and TRAF6, promoting survival and preventing apoptosis. Mutations in TNFRSF13C can lead to common variable immunodeficiency (CVID) and other B-cell-related disorders. The gene is also implicated in autoimmune diseases and certain lymphomas.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• BAFF signaling in B-cell survival (NF-κB pathway)

• TNF receptor superfamily signaling

• B-cell receptor signaling

• Apoptosis regulation

• Primary immunodeficiency pathways

The BAFF-R protein (UniProt Q96RJ3) is a 184-amino acid type III transmembrane receptor with a single extracellular cysteine-rich domain (CRD) that binds BAFF. It lacks a signal peptide and has a short cytoplasmic tail containing TRAF-binding motifs. Upon BAFF binding, BAFF-R recruits TRAF3 and TRAF6, leading to activation of the non-canonical NF-κB pathway (processing of p100 to p52) and canonical NF-κB pathway, promoting B-cell survival and maturation. The protein is expressed as a homotrimer on the cell surface. Mutations affecting the CRD or cytoplasmic domain disrupt ligand binding or signaling, causing immunodeficiency.