IL12RB1 Gene: Function, Mutations, and Associated Diseases

The IL12RB1 gene encodes the beta 1 subunit of the interleukin-12 receptor, a type I transmembrane protein essential for IL-12 signaling. This receptor subunit forms a heterodimer with IL12RB2 to mediate cellular responses to IL-12, including induction of interferon-gamma (IFN-γ) production and promotion of Th1 immune responses. Loss-of-function mutations in IL12RB1 cause Mendelian susceptibility to mycobacterial disease (MSMD), characterized by severe infections with weakly virulent mycobacteria and Salmonella.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• IL-12 signaling pathway

• JAK-STAT signaling pathway

• Th1 and Th2 cell differentiation

• Cytokine-cytokine receptor interaction

IL12RB1 is a 662-amino acid transmembrane glycoprotein that forms the beta 1 subunit of the IL-12 receptor. It binds IL-12 with low affinity and associates with IL12RB2 to create a high-affinity receptor complex. The intracellular domain contains conserved box 1 and box 2 motifs required for JAK2 association and STAT4 activation. Defects in this protein result in complete or partial loss of IL-12 responsiveness, leading to impaired IFN-γ production and increased susceptibility to intracellular pathogens.