TAS2R60

TAS2R60 is a member of the TAS2R family of bitter taste G protein-coupled receptors that remains pharmacologically orphaned, as no agonist was identified among 106 tested bitter compounds even when expressed as major haplotype variants in heterologous cell-based assays, indicating high ligand selectivity (PMID:23632330). Genetic variation in TAS2R60 is associated with individual differences in bitter taste perception of basil and the HIV drug lopinavir/ritonavir, supporting its functional relevance as a gustatory receptor (PMID:22977065, PMID:28923290). TAS2R60 mRNA is also expressed in human skin with variation by body site, sex, and age, though the functional significance of this extraoral expression is uncharacterized (PMID:30332676).

1. 2012 Low

   Whether TAS2R60 contributes to individual variation in bitter taste perception was unknown; genotype-phenotype analysis linked TAS2R60 SNPs to differences in bitterness ratings, establishing it as a functionally relevant bitter taste receptor locus in humans.

   Evidence Genotype-phenotype association in adult twins with SNP genotyping of TAS2R60 and sensory ratings of basil

   PMID:22977065

   Open questions at the time

   • Association study without direct receptor activation assay; causality not established
   • No ligand identified for TAS2R60
   • Mechanism by which TAS2R60 variants alter perception is unknown
2. 2013 Medium

   Whether TAS2R60 could be deorphanized by screening known bitter compounds was tested; the receptor failed to respond to any of 106 agonists in functional assays, establishing that it is highly selective for as-yet-unidentified bitter ligands.

   Evidence Heterologous expression of major haplotype variants in calcium-mobilization cell-based assay with 106 bitter compounds

   PMID:23632330

   Open questions at the time

   • The cognate agonist(s) remain unidentified
   • Downstream signaling pathway not directly characterized for TAS2R60
   • Only one assay format used; alternative readouts could reveal low-efficacy agonists
3. 2017 Low

   Whether TAS2R60 variation influences perception of pharmaceutical compounds was unknown; genotype-phenotype analysis associated TAS2R60 variants with bitterness and irritation ratings of lopinavir/ritonavir, extending the receptor's relevance to drug taste.

   Evidence Genotype-phenotype analysis in genotyped sensory panel using generalized labeled magnitude scales for Kaletra

   PMID:28923290

   Open questions at the time

   • Association-based; no direct demonstration that lopinavir activates TAS2R60
   • Irritation component may involve non-gustatory pathways
   • Not independently replicated
4. 2018 Low

   Whether TAS2R60 is expressed outside taste tissue was unknown; mRNA detection in human skin demonstrated extraoral expression that varies by anatomical site, sex, and age.

   Evidence Gene-specific mRNA quantification in freshly biopsied and GTEx autopsy skin samples

   PMID:30332676

   Open questions at the time

   • Protein-level expression in skin not confirmed
   • Functional role of TAS2R60 in skin is entirely unknown
   • Signaling partners in non-gustatory tissues not identified

• TAS2R60 remains an orphan receptor: its cognate bitter ligand(s), activation mechanism, downstream signaling effectors, and physiological role in extraoral tissues are all uncharacterized.
• No agonist identified despite screening of 106 compounds
• No structural or mutagenesis data to define the ligand-binding pocket
• Functional consequence of extraoral expression is unknown