TAS2R31
receptor / receptor-tas2r31
TAS2R31 is a human bitter taste receptor of the 5-member TAS2R30-46 subfamily encoded in a region of high linkage disequilibrium on chromosome 12 (formerly known as TAS2R44). Responds to saccharin, acesulfame K, and quinine.
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Reading the bitterness
TAS2R31 is a human bitter taste receptor, formerly called TAS2R44, and is one of the 5 receptors that comprise the TAS2R30-46 subfamily clustered on chromosome 12; it is described as responding to saccharin, acesulfame K, and quinine. A Val240Ile variant in this gene appears to be linked to both how bitterly one perceives quinine and the preference one holds for grapefruit juice. In a study of 246 adults, those homozygous for Val240 (individuals with identical copies of the gene inherited one from each parent) rated the bitterness of quinine as low (21.5), while those homozygous for Ile240 rated it higher (30.8). Concurrently, the preference for sugar-free grapefruit juice, judged from memory, was also higher in Val240 homozygotes (9.3 versus −16.53). The authors discuss the possibility that what was previously reported as an association with TAS2R19 may actually have reflected strong linkage disequilibrium (a state in which nearby genes tend to be inherited together) with TAS2R31. However, it is important to note that the grapefruit preference was based on memory rather than on an actual taste evaluation.
The bitter aftertaste perception of saccharin and acesulfame K has also been linked to variants in TAS2R31. In a study examining the gene sequences of the entire TAS2R30-46 cluster, 30 markers were initially associated with the response to these sweeteners, but the region showed strong linkage disequilibrium, and upon closer inspection, most of these apparent associations arose from linkage to a variant in TAS2R31. In fact, TAS2R31 has been confirmed to carry 4 missense variants (variants that alter amino acids) that each have independent effects on receptor response.
As a tool for investigating the function of this receptor, the compound GIV3727 is known to inhibit the response to acesulfame K at an IC50 of 6.4 micromolar and to saccharin at an IC50 of 7.9 micromolar in cells expressing hTAS2R31. However, among the 18 human bitter taste receptors tested, it inhibits 6 of them including TAS2R31, so it is not selective for TAS2R31 alone.
Sources for this overview
Quinine Bitterness and Grapefruit Liking Associate with Allelic Variants in TAS2R31
Checked for this overview: Verified the numerical values of quinine bitterness ratings and grapefruit preference scores stratified by Val240Ile variant.
Genomic, genetic and functional dissection of bitter taste responses to artificial sweeteners
Checked for this overview: Verified the mechanistic background for the possibility that the TAS2R19 association was a product of linkage disequilibrium. / Verified the result that the association of 30 markers was consolidated into the TAS2R31 variant through linkage disequilibrium.
Modulation of bitter taste perception by a small molecule hTAS2R antagonist
Checked for this overview: Verified the IC50 values and inhibition of 6 receptors including TAS2R31 by GIV3727.
Follow the connections
grapefruit juice →has liking associated with→ TAS2R31
TAS2R31 →mediates individual variati…→ saccharin
GIV3727 →antagonizes→ TAS2R31
Structured claims — open a section to read each claim's confidence, evidence and limits
Sensory (1)
Scope: 246 adults (mostly of European ancestry). Recalled liking of unsweetened grapefruit juice was rated on a bipolar hedonic scale
Note: A parallel association was seen with quinine bitterness (21.5 versus 30.8 gLMS). The authors discuss the possibility that the earlier TAS2R19 association reflects linkage disequilibrium with TAS2R31. The verified agonist of TAS2R31 is quinine, not naringin or limonin.
Show data
ingredient-grapefruit-juice —has_liking_associated_with→ receptor-tas2r31Mechanism and receptors (2)
Scope: Full-gene sequencing of TAS2R30-46 in 60 white subjects, taste responses to both sweeteners, and in vitro assays of receptor alleles. 30 markers were initially associated at P < 0.001
Show data
receptor-tas2r31 —mediates_variation_in_bitterness_of→ compound-saccharinScope: Calcium imaging in HEK293 cells stably or transiently expressing a single hTAS2R together with the chimeric G protein G16gust44. The panel screen tested antagonists at 25 uM
Note: Identified from a screen of 17,854 compounds, which yielded 139 candidate antagonists. The authors conclude it is most likely an orthosteric, non-surmountable antagonist: 25 uM GIV3727 shifted the agonist EC50 by 3- to 10-fold and reduced the maximal signal amplitude by 35-70%.
Show data
compound-giv3727 —antagonizes→ receptor-tas2r31