IL12RB2 Gene

The IL12RB2 gene is a protein-coding gene located at chromosome 1p31.3. The protein encoded by the IL12RB2 gene is a type I transmembrane protein, a subunit of the interleukin-12 receptor complex. Coexpression of this protein and the IL12RB1 protein encoded by the IL12RB1 gene results in heterodimeric formation of the high-affinity IL12 binding site. Activation of this receptor by its ligand IL12, results in IL12-dependent signaling coupled to the JAK2/STAT4 pathway. Promotes proliferation of T cells as well as NK cells. Promotes the development of T cells to the Th1 phenotype by strongly increasing IFN-gamma production.

Several transcript variants have been found for this gene, encoding different isoforms and non-protein coding transcripts.

Expression of this gene is upregulated by interferon gamma in Th1 cells and plays a role in Th1 cell differentiation. Activation occurs in a number of infectious diseases such as Crohn's disease and leprosy. In oral lichen planus, L12RB2 is increased in expression (Jeon SH et al. 2015).

SSC: A single nucleotide polymorphism (SNP) at the IL12RB2 locus revealed a genetic association of IL12RB2 with systemic scleroderma (SSC) in a genome-wide association study (GWAS). These results suggest a relevant role of the interleukin-12 pathway in the pathogenesis of SSC (Bossini-Castillo L et al).

Primary biliary cholangitis (PBC): In primary biliary cholangitis, strong associations with SNPs located in the IL12RB2 gene can be detected. PBC carriers with IL12RB2 polymorphisms have an increased rate of cirrhosis with significantly higher AMA titers (Wasik U et al. 2017).

Adenocarcinoma of the lung: Polymorphisms (LOF mutation) in the L12RB2 gene correlate with an increased risk of adenocarcinoma of the lung (Prigione I et al. 2016).

1. Bossini-Castillo L et al. (2012) GWAS follow-up study reveals the association of the IL12RB2 gene with systemic sclerosis in Caucasian populations. Hum Mol Genet 21:926-933.
2. Jeon SH et al. (2015) The potential of interleukin 12 receptor beta 2 (IL12RB2) and tumor necrosis factor receptor superfamily member 8 (TNFRSF8) gene as diagnostic biomarkers of oral lichen planus (OLP). Acta Odontol Scand 73:588-594..
3. Prigione I et al. (2016) IL12RB2 polymorphisms correlate with risk of lung adenocarcinoma. Immunobiology 221:291-299.
4. Wasik U et al (2017) Polymorphisms of IL12RB2 May Affect the Natural History of Primary Biliary Cholangitis: A Single Centre Study. J Immunol Res 2017:2185083.