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OR2T6

Summary

Olfactory Receptor Family 2 Subfamily T Member 6 (OR2T6) is a human gene encoding a G-protein coupled receptor (GPCR) predominantly expressed in the olfactory epithelium. It is responsible for the initiation of sensory signals that trigger the perception of smell. In genetic epidemiology, a nonsynonymous variant within OR2T6 (rs6587467) is utilized as a high-confidence genetic instrument for onion preference in Chemosensory Mendelian Randomization studies.

Biological Function and Expression

OR2T6 belongs to the large family of olfactory receptors that interact with odorant molecules in the nasal cavity to activate a G-protein-mediated signaling cascade. - Tissue Specificity: Studies using transcriptomics and proteomics show that its expression is highly localized to the olfactory epithelium (as of 2026-07-19), providing high biological specificity for chemosensory traits. - Ligand Binding: It detects volatile compounds, potentially including organosulfur compounds and other key flavor volatiles present in onions and related foods.

Clinical and Epidemiological Significance

In a dietary Mendelian randomization framework developed by Evans Lab, the OR2T6 missense variant rs6587467 (G/T allele) was identified as a robust, non-pleiotropic instrument for onion liking. Each point increase on a 9-point Hedonic scale of genetically proxied onion liking (linked to OR2T6 variation) was causally associated with: - Blood Pressure: A decrease of -1.256 mmHg in systolic blood pressure and -0.716 mmHg in diastolic blood pressure. - Metabolic Risk: A reduced risk of type 2 diabetes (Odds Ratio = 0.856).

This makes OR2T6 a critical gene of interest for studying sensory-driven dietary behaviors and their cardiometabolic consequences.

Citations

  • Hwang, L. D., Lin, C., Evans, D. M., Martin, N. G., Reed, R. D., & Joseph, P. V. (2026). A biologically informed framework for instrument selection in dietary Mendelian randomization using chemosensory genetics. BMC Medicine, 24:359. DOI: 10.1186/s12916-026-04966-x. Source paper: s12916-026-04966-x.pdf
  • UniProt Consortium. OR2T6 Entry: Q8NHC8 (as of 2026-07-19)