BTNL2 gene

The BTNL2 gene (BTNL2 stands for butyrophilin like 2) is a protein-coding gene located on chromosome 6p21.32. The BTNL2 gene encodes a major histocompatibility complex class II associated type I transmembrane protein that belongs to the butyrophilin-like B7 family of immunoregulators . This protein is thought to be involved in immunosurveillance. It functions as a "negative T cell regulator" by decreasing T cell proliferation and cytokine release.

The encoded protein contains an N-terminal signal peptide, two pairs of immunoglobulin-like domains separated by a heptad peptide sequence, and a C-terminal transmembrane domain.

Naturally occurring mutations in this gene are associated with sarcoidosis, rheumatoid arthritis, myositis, type 1 diabetes, systemic lupus erythematosus, roazea (Awosika O et al. (2018), acute coronary syndrome and prostate cancer (Lin Y et al. 2015; Du Y et al. 2022).

Ulcerative colitis, inflammatory bowel disease: A rare coding variant p.G454C in the BTNL2 gene within the major histocompatibility complex was significantly associated with an increased risk of IBD (p = 9.65x10-10, OR = 2.3[95% CI = 1.75-3.04]). This finding is independent of the known common associated CD and UC variants at this locus (Prescott NJ et al. 2015).

1. Awosika O et al. (2018) Genetic Predisposition to Rosacea. Dermatol Clin 36):87-92
2. Du Y et al. (2022) Cancer cell-expressed BTNL2 facilitates tumor immune escape via engagement with IL-17A-producing γδ T cells. Nat Commun 13:231.
3. Lin Y et al. (2015) BTNL2 gene polymorphism and sarcoidosis susceptibility: a meta-analysis. PLoS One 10:e0122639.
4. Milman N et al. (2011) The BTNL2 A allele variant is frequent in Danish patients with sarcoidosis. Clin Respir J 5:105-111.
5. Ozdemir M et al. (2014) Is there a genetic predisposition for Turkish patients with sarcoidosis in the 329-bp region containing the BTNL2 rs2076530 polymorphism? Turk J Med Sci 44:590-594.
6. Prescott NJ et al. (2015) Pooled sequencing of 531 genes in inflammatory bowel disease identifies an associated rare variant in BTNL2 and implicates other immune related genes. PLoS Genet 11:e1004955.