TAS2R38

receptor / receptor-tas2r38

TAS2R38 is a human bitter taste receptor with the common haplotypes PAV and AVI. It responds to phenylthiocarbamide and propylthiouracil, as well as to goitrin and sinigrin.

On this page (8 sections)

Overview
Sources for this overview (6)
Topic hubs
Follow the connections
Related entries (10)
Composition and content (1)
Sensory (6)
Mechanism and receptors (8)

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Reading the bitterness

TAS2R38 is the most repeatedly confirmed genotype-taste correspondence for sensitivity to two bitter compounds: phenylthiocarbamide (PTC) and propylthiouracil (PROP). This receptor has two main haplotypes, PAV and AVI. When expressed in heterologous cells, the PAV type responds to PTC and PROP at micromolar concentrations, whereas the AVI type did not respond even at 1 mM. In a study examining 330 chromosomes worldwide, PAV (hsA) was found at a frequency of 0.55 and AVI (hsG) at 0.38, with the two together accounting for more than 90% of the chromosomes in the sample.

This haplotype also appears in bitterness perception of Brassica vegetables. In a trial of 69 UK consumers rating 7 arugula accessions, the main effect of genotype on bitterness ratings was significant, but the difference between genotypes for each accession could not be separated. In a trial of 74 consumers rating turnips cooked in 4 different ways, PAV/PAV subjects tended to rate bitterness higher than PAV/AVI or AVI/AVI subjects, but the difference was statistically significant only for stir-frying. In both studies, the effect of genotype on the perception of bitterness and its effect on preference for the vegetable were separate phenomena. Genotype influenced bitterness ratings, but was not a strong predictor of actual eating preferences.

Beyond taste, TAS2R38 is also involved in defense of the nose and throat. In experiments with human nasal and paranasal sinus epithelium cultured from surgical specimens, TAS2R38 responded to quorum-sensing molecules (acylhomoserine lactone) produced by gram-negative bacteria such as Pseudomonas aeruginosa, caused the production of nitric oxide to speed up ciliary beating, and showed a bacterial-killing function. The fraction of live Pseudomonas aeruginosa was 14% in cultures of PAV/PAV type, but remained at 80% in PAV/AVI type and 70% in AVI/AVI type. The same research group also reported that no PAV/PAV homozygotes were found among patients with gram-negative bacteria in the paranasal sinuses, but this is a retrospective correlation, and details such as patient numbers have not been confirmed.

On the other hand, the notion that 「苦味に敏感な人ほどアブラナ科野菜を苦く感じて避ける」 (in translation: "people who are more sensitive to bitterness perceive Brassica vegetables as more bitter and avoid them") is not that simple in the data. In both the arugula and turnip studies, genotype influenced bitterness ratings but did not significantly affect the clustering of preferences or the degree of liking for the vegetable itself. A meta-analysis of 36 studies in adults also reported that the association between bitterness sensitivity and vegetable and legume consumption was small and not significant. Regarding why TAS2R38 variation is maintained at an intermediate frequency worldwide, there is a hypothesis of balancing selection, but the authors themselves state that they cannot reject neutrality under standard population-history assumptions and can only reject it when assuming a specific population expansion; the mechanism remains uncertain.

Sources for this overview

The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception
Bufe B; Breslin PA; Kuhn C; Reed DR; Tharp CD; Slack JP; Kim UK; Drayna D; Meyerhof W / 2005 / journal article / full text checked
Checked for this overview: Confirmed the in vitro experimental result that PAV and AVI types show different responses to 1 mM PTC.
Natural selection and molecular evolution in PTC, a bitter-taste receptor gene
Wooding S; Kim UK; Bamshad MJ; Larsen J; Jorde LB; Drayna D / 2004 / journal article / full text checked
Checked for this overview: Confirmed the frequency of PAV 0.55 and AVI 0.38 in 330 worldwide chromosomes. / Confirmed the limitation that the balancing-selection hypothesis depends on population-history assumptions.
The influence of phytochemical composition and resulting sensory attributes on preference for salad rocket (Eruca sativa) accessions by consumers of varying TAS2R38 diplotype
Bell L; Methven L; Wagstaff C / 2017 / journal article / full text checked
Checked for this overview: Confirmed the significant effect of genotype on bitterness rating in the trial of 69 arugula consumers. / Confirmed that genotype is not a strong predictor of preference.
Consumer Liking of Turnip Cooked by Different Methods: The Influence of Sensory Profile and Consumer Bitter Taste Genotype
Nor NDM; Mullick H; Zhou X; Oloyede O; Houston-Price C; Harvey K; Methven L / 2023 / journal article / full text checked
Checked for this overview: Confirmed that a significant difference was observed in the turnip trial of 74 consumers only for stir-frying. / Confirmed the lack of a significant effect of genotype on liking for turnips.
T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection
Lee RJ; Xiong G; Kofonow JM; Chen B; Lysenko A; Jiang P; Abraham V; Doghramji L; Adappa ND; Palmer JN; Kennedy DW; Beauchamp GK; Doulias PT; Ischiropoulos H; Kreindler JL; Reed DR; Cohen NA / 2012 / journal article / full text checked
Checked for this overview: Confirmed the response to AHL and the genotype-specific survival rates of bacteria at 14%, 80%, and 70%. / Confirmed the retrospective correlation that no PAV/PAV homozygotes were found among infected patients.
Bitter taste sensitivity is minimally associated with adult food preferences and intake, with a negative association to carbohydrate consumption: A systematic review and meta-analysis
Shareef A; Irwin C; Vincze L; Rigby R; Jani R / 2026 / review / abstract checked
Checked for this overview: Confirmed the result from a meta-analysis of 36 studies that the association with consumption is small.

Follow the connections

TAS2R38 →is activated in vitro by→ goitrin

TAS2R38 →modulates the perceived int…→ bitterness →can be measured separately …→ astringency

TAS2R38 →determines the acceptance of→ Brassica vegetables

TAS2R38 →’s genotype is associated w…→ lingonberry →— sensory attribute→ bitterness

Structured claims — open a section to read each claim's confidence, evidence and limits

Composition and content (1)

TAS2R38In 330 chromosomes worldwide, the taster haplotype hsA (PAV) is at 0.55 and the non-taster haplotype hsG (AVI) is at 0.38. Together they account for more than 90% of the sample chromosomes, and the allele frequencies are similar across populations (FST 0.056).’s major haplotypes occur at intermediate frequencies: supported

Scope: 165 individuals and 330 chromosomes collected from populations in Africa, Asia, Europe, and North America.

Note: Population differences exist (FST is significantly different from 0 at P<.025), but lower than typical for nuclear genes, as stated in the original. Regional allele-frequency values by location are in a table in the manuscript and have not been entered here.

Both the hsA and hsG haplotypes were found at intermediate frequencies of 0.55 and 0.38, respectively, accounting for more than 90% of the sample chromosomes. hsA is associated with the taster phenotype and hsG with the non-taster phenotype. Both haplotypes were observed at similar frequencies in most populations, and FST (0.056) was significantly different from zero (P <.025) but lower than values typically observed for nuclear genes.

Limitations: Allele frequencies by population are shown in a table in the paper and have not been transcribed here. Sample size per population is small (7–45 individuals).

Source: Natural selection and molecular evolution in PTC, a bitter-taste receptor gene (Wooding S; Kim UK; Bamshad MJ; Larsen J; Jorde LB; Drayna D, 2004) · full text checked

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receptor-tas2r38 —has_major_haplotypes_at_intermediate_frequencies→ "In 330 chromosomes worldwide, the taster haplotype hsA (PAV) is at 0.55 and the non-taster haplotype hsG (AVI) is at 0.38. Together they account for more than 90% of the sample chromosomes, and the allele frequencies are similar across populations (FST 0.056)."

claim: clm-tas2r38-haplotype-frequencies-worldwide / type: taxonomy / updated: 2026-08-30

Sensory (6)

TAS2R38 modulates the perceived intensity of bitternesssupported

Scope: UK adult consumers who rated rocket (arugula) lines (genotyped n=69) and cooked turnip (n=74). TAS2R38 PAV/PAV, PAV/AVI, and AVI/AVI diplotypes

Note: The main effect of genotype on bitterness was significant in both studies, but in neither study did pairwise comparisons within individual samples separate the genotypes.

Sum-of-squares ANOVA showed that TAS2R38 genotype had a significant effect on bitterness perception (P < 0.02). While the authors note that this suggests a significant effect on bitterness perception, they also state that the ANOVA showed no significant difference between genotypes within any particular rocket line, that the diplotype effect was less pronounced than originally hypothesized, and that there was a general tendency for non-tasters to score rocket bitterness lower than medium tasters or supertasters.

Limitations: The main effect does not survive as a pairwise difference within lines. Recruitment was around a single university, with 76.7% of participants female, limiting generalizability. Other TAS2R genotypes and fungiform papillae density were not measured, and the authors list these as factors that could contribute.

Source: The influence of phytochemical composition and resulting sensory attributes on preference for salad rocket (Eruca sativa) accessions by consumers of varying TAS2R38 diplotype (Bell L; Methven L; Wagstaff C, 2017) · full text checked

TAS2R38 genotype had a significant effect on bitterness perception (F(2,256) = 4.14, p = 0.02); across all samples, PAV/PAV consumers tended to rate bitterness intensity higher than PAV/AVI (p = 0.07) and AVI/AVI consumers (p = 0.05) (27.6 versus 16.9 and 16.4). There was no significant difference in bitterness intensity scores between PAV/AVI and AVI/AVI consumers (p = 0.99). It was only for stir-fried turnip that PAV/PAV consumers rated bitterness intensity significantly higher than PAV/AVI (p = 0.02) and AVI/AVI (p = 0.001) consumers.

Limitations: Pairwise contrasts between PAV/PAV and the other diplotypes remained at only p = 0.05 and p = 0.07 across all samples, and significant separation held for only 1 cooking method. 7 consumers with rare genotypes were excluded from the analysis. The authors themselves state that the sample is small and UK-only.

Source: Consumer Liking of Turnip Cooked by Different Methods: The Influence of Sensory Profile and Consumer Bitter Taste Genotype (Nor NDM; Mullick H; Zhou X; Oloyede O; Houston-Price C; Harvey K; Methven L, 2023) · full text checked

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receptor-tas2r38 —modulates_perceived_intensity_of→ sensation-bitter

claim: clm-tas2r38-brassica-bitterness-perception / type: sensory / updated: 2026-08-30

TAS2R38 determines the acceptance of Brassica vegetablescontested

Scope: Consumer liking and acceptance of Brassica vegetables as a function of TAS2R38 diplotype

Note: This review-level framing was directly tested in 2 UK consumer studies and was not supported: the genotype effect on perceived bitterness does not carry through to liking. For rocket, the main basis for acceptance was not bitterness but perceived hotness (pungency).

Contradicts: The authors conclude that the hypothesis that all consumers reject bitter cultivars is not fully supported by the data presented, and the same holds even accounting for human TAS2R38 diplotype; the main basis for acceptance/rejection seems in fact to relate more to the leaves' perceived hotness than to bitterness. The effect of consumer genotype on taste preference was significant in sum-of-squares ANOVA (P < 0.004), but the pairwise comparison scores accounting for interaction with sample were not significant. An effect of TAS2R38 diplotype on liking was observed, but this classification alone was not an accurate predictor of whether an individual would like or dislike Brassica-type vegetables. Diplotype frequency did not differ significantly between the discriminating cluster and the indifferent cluster (C1 P = 0.918; C2 P = 0.564; between clusters P = 0.919). The correlation between taste preference and bitterness perception across the whole cohort was significant but weak (r = -0.227, P < 0.0001).

Limitations: Rocket is a Brassica but not Brassica oleracea, so extension to cabbage-type crops is an inference. The genotype's main effect is significant in the omnibus test and fails only in pairwise comparisons, so this is a failure to localize the effect rather than a demonstrated null. The correlation between bitterness and liking is weak but in the expected negative direction.

Contradicts: Although TAS2R38 genotype had a significant effect on bitterness perception, this bitterness genotype had no significant effect on either taste liking (F(2,70) = 0.99, p = 0.38) or overall liking (F(2,70) = 1.05, p = 0.35) of cooked turnip, and the interaction between cooking method and TAS2R38 was not significant for either taste liking (F(6,210) = 0.77, p = 0.59) or overall liking (F(6,210) = 1.38, p = 0.23). The ratio of tasters to non-tasters was similar across all 3 liking clusters (63/37, 67/33, 67/33 percent), and the authors concluded that the separation of these clusters was not driven by bitterness genotype.

Limitations: This is a null result in a sample of 74 with 3 genotype groups, and the authors themselves explicitly note that it is small and UK-limited. The absence of a significant effect is not evidence of the absence of an effect. Even combining bitterness and sweetness perception explains only 15.7% of the variance in taste liking (adjusted R2 = 0.157), and most of the variance in liking is explained by neither taste attribute.

Context: This review states that the main sensory attributes involved in these vegetables are a characteristic sharp bitterness and a distinctive aroma, that these characteristics often lead consumers to reject this group of vegetables, and that because some people do not perceive the unpleasant sensation, individual variation in bitterness perception and sensitivity may plausibly be involved.

Limitations: Abstract-level and narrative. Included only to record the framing that the primary consumer studies go on to test; it reports no quantitative association between genotype and acceptance, and is not treated as support for this claim.

Source: Bitter taste of Brassica vegetables: The role of genetic factors, receptors, isothiocyanates, glucosinolates, and flavor context (Wieczorek MN; Walczak M; Skrzypczak-Zielinska M; Jelen HH, 2018) · abstract checked

Contradicts: The pooled association between bitterness sensitivity in adults (as the PROP/PTC phenotype or the TAS2R38 genotype) and vegetable and legume liking and intake was small and non-significant across the 36 studies meta-analyzed, and the authors conclude that bitterness sensitivity explains little of the variation in adult dietary patterns.

Limitations: Because the vegetable and legume category is broader than Brassica, this is not a direct test of Brassica but a population-level counter-evidence to the general claim. Studies of children and adolescents, where genotype effects are often reported to be stronger, are excluded by design.

Source: Bitter taste sensitivity is minimally associated with adult food preferences and intake, with a negative association to carbohydrate consumption: A systematic review and meta-analysis (Shareef A; Irwin C; Vincze L; Rigby R; Jani R, 2026) · abstract checked

Show data

receptor-tas2r38 —determines_acceptance_of→ ingredient-brassica

claim: clm-tas2r38-drives-brassica-rejection / type: sensory / updated: 2026-08-30

TAS2R38Pediatric liquid formulations: 48% (57/119) of children carrying at least one copy of the sensitive TAS2R38 A49P allele (AP or PP) reported problems accepting the liquid formulation, compared to 28% (14/50) of AA children (chi-square = 5.72, df = 1, p = 0.02).’s genotype is associated with reported rejection of: preliminary

Scope: 172 children aged 3–10 years and 130 mothers recruited in Philadelphia, USA. Measured adherence was not assessed; rather, retrospective interviews about past medication-taking experience were conducted.

Note: The outcome is based on self-reported past experience, a single study population. Of 172 children, 19 (11%) did not answer the rejection question; 84.2% of these non-respondents carried the bitter-sensitivity genotype, so the direction of non-response bias is not neutral. The authors note that TAS2R38 is unlikely to be sensitive to every bitter compound in the drug, and it may partly serve as a proxy for general taste ability.

Children with at least one copy of the sensitive TAS2R38 allele (48%, 57/119 AP or PP) reported more problems accepting the liquid formulation than children without the bitter allele (28%, 14/50 AA) (chi-square = 5.72, df = 1, p = 0.02). Genotype distribution in the 169 genotyped children was AA 29.6%, AP 45.6%, PP 24.8%, and was in Hardy-Weinberg equilibrium.

Limitations: The outcome is self-reported past problems; observed rejection or adherence was not measured. Of the 172, 19 (11%) did not answer the rejection question; 84.2% of these non-respondents carried the AP/PP genotype and were also significantly younger (mean 6.2 vs. 8.0 years, p < 0.0001). Only one bitter taste receptor gene was genotyped.

Source: Children's perceptions about medicines: individual differences and taste (Mennella JA; Roberts KM; Mathew PS; Reed DR, 2015) · full text checked

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receptor-tas2r38 —has_genotype_associated_with_reported_rejection_of→ "Pediatric liquid formulations: 48% (57/119) of children carrying at least one copy of the sensitive TAS2R38 A49P allele (AP or PP) reported problems accepting the liquid formulation, compared to 28% (14/50) of AA children (chi-square = 5.72, df = 1, p = 0.02)."

claim: clm-tas2r38-liquid-medicine-rejection / type: sensory / updated: 2026-08-30

TAS2R38lingonberry’s genotype is associated with reported rejection of: supported

Scope: A questionnaire survey of consumption frequency administered to subjects (n=83) with TAS2R38 genotypes determined.

Note: An association is reported in which subjects with bitter-sensitive TAS2R38 genotypes (such as PAV homozygotes) report lower consumption frequency of lingonberries.

An association is reported whereby subjects with bitter-sensitive TAS2R38 genotypes have a lower consumption frequency of lingonberries.

Limitations: This is self-reported data and is not an experimental study controlling bitterness perception and consumption.

Source: Consumption of lingonberries by TAS2R38 genotype and sensory quality of texture-designed lingonberry samples (Mari Sandell; Ulla Hoppu; Saara Lundén; Mari Salminen; Tuuli Puolimatka; Oskar Laaksonen; Kirsi Laitinen; Anu Hopia, 2015) · abstract checked

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receptor-tas2r38 —has_genotype_associated_with_reported_rejection_of→ ingredient-lingonberry

claim: clm-lingonberry-tas2r38-consumption / type: sensory / updated: 2026-09-02

goitrin — perceived bitterness is associated with: TAS2R38preliminary

Scope: Layer: solution (psychophysical threshold measurement). A study of 50 subjects examining the association between threshold taste responses to goitrin, PROP, and PTC, and TAS2R38 genotype/functional variants.

Note: Confirmed at abstract level only. A quantitative finding showing that TAS2R38 genetic variation alone cannot explain most of the variance in goitrin response (the authors suggest the involvement of other factors).

"threshold responses to goitrin were associated with responses to both PROP (P = 8.9 x 10(-4); r(s) = 0.46) and PTC (P = 7.5 x 10(-4); r(s) = 0.46)... goitrin responses were significantly associated with mutations in TAS2R38 (P = 9.3 x 10(-3)), but the same mutations accounted for a smaller proportion of variance in goitrin response (r(2) = 0.16) than for PROP (r(2) = 0.50) and PTC (r(2) = 0.57)."

Limitations: Confirmed at abstract level. Both the correlation coefficient (rs) and the variance-explained figure (r2) are given together; the threshold's own absolute value (concentration) is not stated in the abstract.

Source: Genetics and bitter taste responses to goitrin, a plant toxin found in vegetables (Wooding S; Gunn H; Ramos P; Thalmann S; Xing C; Meyerhof W, 2010) · abstract checked

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compound-goitrin —has_perceived_bitterness_associated_with→ receptor-tas2r38

claim: clm-w71a1-goitrin-threshold-correlates-prop-ptc / type: sensory / updated: 2026-09-07

supertaster — perceived bitterness is associated with: TAS2R38supported

Scope: Layer: solution. 243 participants were presented, in duplicate, with 5 PROP concentrations (0.032, 0.1, 0.32, 1.0, 3.2 mM) and rated bitterness on the generalized Labeled Magnitude Scale (gLMS). TAS2R38 and TAS2R4 genotypes were determined from salivary DNA.

"the TAS2R38 diplotype explained 29.3% of the variation in the perceived bitterness for 3.2mM PROP [F(1,216) = 89.4 p < 0.0001]." "The TAS2R4 diplotype explained 7.7% of the variation for the highest concentration of PROP (3.2 mM) [F(1,206) = 17.20; p < 0.0001]." "The mean ratings for the 26 individuals homozygous for both of the low-functioning haplotypes (dual AVI and FVS homozygotes) had a mean rating of 18.4 (±3.9) compared to a mean of 56.8 (±3.9) for the 27 individuals homozygous for both of the high-functioning haplotypes (dual PAV and SLN homozygotes)-a ~3.1 fold difference."

Limitations: TAS2R4's response to PROP was confirmed only weakly in vitro at 3 mM (a high concentration), and the paper itself states that its physiological significance requires further verification.

Source: Differential Activation of TAS2R4 May Recover Ability to Taste Propylthiouracil for Some TAS2R38 AVI Homozygotes (Nolden AA; Behrens M; McGeary JE; Meyerhof W; Hayes JE, 2024) · full text checked

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concept-supertaster —has_perceived_bitterness_associated_with→ receptor-tas2r38

claim: clm-w71d1-prop-bitterness-tas2r38-tas2r4-variance / type: sensory / updated: 2026-09-07

Mechanism and receptors (8)

TAS2R38goitrin is activated in vitro by: supported

Scope: Allele-specific in vitro functional assay of the 6 TAS2R38 haplotypes, confirmed by full-gene sequencing in 56 white subjects

Note: Gives a receptor-level link connecting Brassica glucosinolate chemistry to the PROP/PTC sensitivity axis. The abstract has no per-compound EC50 or threshold values, so a potency ranking is not recorded.

Genetic diversity was confirmed by full-gene sequencing in 56 white subjects, and allele-specific responses to 5 TAS2R38 agonists (PTC, PROP, goitrin, methimazole, and sinigrin) were analyzed by in vitro assay. However, the number of subjects for detection-threshold measurement differed by compound: all 56 subjects for salicin, PTC, PROP, goitrin, and methimazole, but only 25 (a subpopulation) for sinigrin. The genotype association with threshold was strongly significant for PTC/PROP/goitrin/methimazole (the thioamide compounds), at P<0.005 and β>1.85 for all 3 SNPs, whereas for sinigrin all 3 SNPs were significant but with higher P-values (0.04, 0.03, 0.03), and the authors themselves state that power is limited by the small sample of N=25. The P<0.001 for the PAV/AVI haplotype is mainly the value for the thioamide compounds.

Limitations: It should be noted explicitly that the genotype–threshold association for sinigrin is statistically weaker than for the thioamide compounds and comes from a small sample (N=25).

Source: Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception (Behrens M; Gunn HC; Ramos PC; Meyerhof W; Wooding SP, 2013) · full text checked

Verbatim: 'Functional expression studies demonstrate that five different haplotypes from the hTAS2R38 gene code for operatively distinct receptors.' The PAV receptor responded with an EC50 of 1.1 uM (PTC) and 2.1 uM (PROP), while 'hTAS2R38-AVI did not respond to PTC or PROP concentrations as high as 1 mM.' PVI, AAI, and AAV responded with EC50 values close to PAV. Concentration–intensity functions and recognition thresholds were measured in 32 subjects of known TAS2R38 diplotype, and one PAV subject's lowest discriminable concentration corresponded to the PAV receptor's in vitro EC50.

Limitations: This study did not test goitrin or sinigrin, so it independently supports the allele-dependent TAS2R38 function axis of this claim (via PTC/PROP), but does not itself support goitrin/sinigrin agonism.

Source: The molecular basis of individual differences in phenylthiocarbamide and propylthiouracil bitterness perception (Bufe B; Breslin PA; Kuhn C; Reed DR; Tharp CD; Slack JP; Kim UK; Drayna D; Meyerhof W, 2005) · full text checked

Context: The full-text Discussion of Eib et al. (2020) mentions the relationship between sinigrin's bitterness and TAS2R38. Verbatim: "Sinigrin is associated with bitterness; this is a basic taste, which is predominantly perceived via the TASTE 2 receptor (TAS2R) family on the tongue (Bell et al., 2018). In particular, sinigrin binds preferably to TAS2R38 (Meyerhof, Kuhn, Chudoba, et al., 2010)." This is not Eib's own measurement but a secondary mention citing the receptor-preference finding of Meyerhof et al. 2010.

Limitations: The primary data are in the Meyerhof 2010 TAS2R source. That source currently has access_status=restricted and review_status=abstract_checked, and the sources.csv notes do not yet mention sinigrin. This line follows the pattern of 『別ソース全文で見つかった一次文献への二次引用』 (in translation: "a secondary citation, within the full text of a different source, to primary literature found there"); once the full text of Meyerhof 2010 itself becomes readable, this line should be replaced with a primary evidence line, or treated, for now, as a provisional secondary citation that needs to be supplemented.

Source: Determination of detection thresholds of sinigrin in water-based matrix and allyl isothiocyanate in water- and oil-based matrices (Eib Sabrina; Ramos Gajek Sarah; Schneider Desiree Janet; Hensel Oliver; Seuss-Baum Ingrid, 2020) · full text checked

Context: In vitro, allelic differences in EC50 for each agonist were not statistically significant, whereas the magnitude of the response (ΔF/F) within the same agonist differed greatly between alleles. PAV responded strongly to all agonists, and AVI did not respond above baseline to any of them. Verbatim: "allelic differences in EC50 within agonists were not statistically significant. In contrast, within-agonist comparisons revealed highly divergent functionality among alleles as measured by ΔF/F."

Limitations: The lack of a significant difference in EC50 may partly reflect a power issue. The correspondence with human thresholds is covered in a separate section of the main text.

Source: Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception (Behrens M; Gunn HC; Ramos PC; Meyerhof W; Wooding SP, 2013) · full text checked

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receptor-tas2r38 —is_activated_in_vitro_by→ compound-goitrin

claim: clm-goitrin-sinigrin-tas2r38-agonists / type: mechanism / updated: 2026-08-30

TAS2R38 explains the bimodal individual variation in phenylthiocarbamideestablished

Scope: Linkage-disequilibrium mapping in unrelated subjects (Kim 2003), genotype-stratified psychophysics (Bufe 2005), threshold phenotyping across 6 haplotypes (Behrens 2013)

A small region on chromosome 7 at 7q shows strong linkage disequilibrium between SNP markers and PTC taste sensitivity in unrelated subjects; this region contains a single TAS2R gene with 3 coding SNPs, giving rise to 5 haplotypes worldwide. These haplotypes fully explain the bimodal distribution of PTC taste sensitivity and account for 55–85% of the variance in PTC sensitivity.

Limitations: Abstract level: the sample size, the population behind the 55–85% range, and the phenotype values for each haplotype are not given in the abstract. The full text in Science is not accessible.

Source: Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide (Kim UK; Jorgenson E; Coon H; Leppert M; Risch N; Drayna D, 2003) · abstract checked

Suprathreshold PTC intensity functions showed a clear separation between every AVI/AVI function and every PAV/PAV function, and all diplotype groups differed significantly from one another at every PTC concentration (p < 0.001).

Limitations: The sample per diplotype group is small. Heterozygotes are intermediate in PTC intensity but resemble PAV/PAV in recognition threshold, so which phenotype is measured matters.

In 56 subjects covering the 6 TAS2R38 haplotypes, the association with detection thresholds for 4 thioamide compounds (PTC, PROP, goitrin, and methimazole) was strongly significant, at P<0.005 and β>1.85 for all 3 SNPs, and P<0.001 for the PAV/AVI haplotype. For sinigrin (only a subpopulation of N=25), all 3 SNPs were also statistically significant, but the P-values, at 0.03–0.04, were higher than for the thioamide compounds, and the authors point to insufficient power from the small sample.

Limitations: Abstract level. Haplotypes other than PAV and AVI showed no association with phenotype, which the authors attribute to their low frequency. It is used here to read the correspondence between genotype and threshold.

Source: Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception (Behrens M; Gunn HC; Ramos PC; Meyerhof W; Wooding SP, 2013) · full text checked

Context: Mean thresholds varied more than 40-fold among compounds (from about 50 µM for PTC to about 2000 µM for sinigrin), and within-compound individual variation ranged from 40-fold for salicin, goitrin, and sinigrin to 8000-fold for PTC. Verbatim: "Mean thresholds varied more than 40-fold among compounds, from a minimum of ~50 µM (PTC) to a maximum of ~2000 µM (sinigrin), whereas within-compound threshold ranges varied from 40-fold (salicin, goitrin, and sinigrin) to 8000-fold (PTC) (Figure 2)."

Limitations: The number of subjects differs by compound (sinigrin uses only a subpopulation).

Source: Genetic, functional, and phenotypic diversity in TAS2R38-mediated bitter taste perception (Behrens M; Gunn HC; Ramos PC; Meyerhof W; Wooding SP, 2013) · full text checked

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receptor-tas2r38 —explains_bimodal_variation_in→ compound-ptc

claim: clm-tas2r38-explains-ptc-sensitivity / type: mechanism / updated: 2026-08-30

TAS2R38phenylthiocarbamide shows a haplotype-dependent in vitro response to: supported

Scope: Heterologous expression of the PAV and AVI variants of TAS2R38 with calcium imaging. PROP tested alongside PTC

Micromolar concentrations of PTC raised cytoplasmic calcium in cells expressing the PAV-type receptor in a concentration-dependent manner, and the receptor responded equally strongly to PROP, whereas hTAS2R38-AVI did not respond even to the high concentration of 1 mM of PTC or PROP (this sentence has been checked verbatim against the source).

Limitations: The EC50 values are in Figure 1C but are not given as numbers in the main text, so potency values are not recorded here.

Context: Places the TAS2R38 result in its contemporaneous context and generalizes the design: the authors state that, until their study, the phenylthiocarbamide receptor hT2R38 had been the only gene directly linked to variation in human bitter taste, and go on to report that polymorphisms in 2 further hT2R genes produce different receptor activity and different taste sensitivity to 3 bitter molecules.

Limitations: Does not retest the PAV and AVI variants of TAS2R38; it supports the allele–receptor-activity design rather than Bufe 2005's specific numbers. An abstract-level extraction.

Source: Specific alleles of bitter receptor genes influence human sensitivity to the bitterness of aloin and saccharin (Pronin AN; Xu H; Tang H; Zhang L; Li Q; Li X, 2007) · abstract checked

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receptor-tas2r38 —has_haplotype_dependent_in_vitro_response_to→ compound-ptc

claim: clm-tas2r38-pav-avi-receptor-function / type: mechanism / updated: 2026-08-30

TAS2R38 — variation is maintained by (proposed): Balancing selection. Accompanied by the hypothesis that the non-taster (AVI) allele encodes a functional receptor for bitter toxins other than PTC, and that heterozygotes perceive a broader repertoire of bitter toxinspreliminary

Scope: Coalescent-theory-based neutrality tests on worldwide TAS2R38 sequence variation, under various assumed population histories

Note: Under standard assumptions, neutrality cannot be rejected; it is rejected only when assuming population expansion (15- to 1000-fold, 1 to 20 ten-thousand years ago) -- a model-dependent inference. The authors themselves state that the mechanism behind the heterozygote-advantage hypothesis is unresolved.

Under standard neutrality assumptions the test could not reject neutrality, but under every population history in which the human population expanded 15- to 1000-fold between 10,000 and 200,000 years ago, the neutrality hypothesis was rejected (two-sided P-value cutoff .025), and the authors interpret this pattern as consistent with balancing natural selection. They hypothesize that the PTC non-taster allele encodes a functional receptor molecule that binds toxic bitter substances other than PTC, giving heterozygotes perception of a broader repertoire of bitter toxins.

Limitations: Rejection of neutrality is conditional on the assumed demographic history, and the authors themselves acknowledge that this substantially affects the conclusion. In the authors' own words, the mechanism maintaining the divergent alleles remains unknown. Recorded as preliminary for this reason.

Source: Natural selection and molecular evolution in PTC, a bitter-taste receptor gene (Wooding S; Kim UK; Bamshad MJ; Larsen J; Jorde LB; Drayna D, 2004) · full text checked

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receptor-tas2r38 —has_variation_maintained_by→ "Balancing selection. Accompanied by the hypothesis that the non-taster (AVI) allele encodes a functional receptor for bitter toxins other than PTC, and that heterozygotes perceive a broader repertoire of bitter toxins"

claim: clm-ptc-nontaster-balancing-selection / type: mechanism / updated: 2026-08-30

TAS2R38Bacterial acyl-homoserine lactone quorum-sensing molecules (C4HSL 200 uM, C12HSL 100 uM) in the human sinonasal epithelium. Drives calcium-dependent nitric oxide production, an increase in ciliary beat frequency, and direct bacterial killing is activated by supported

Scope: Polarized primary human sinonasal epithelial cultures genotyped for the TAS2R38 PAV/AVI haplotype. In killing of Pseudomonas aeruginosa strain PAO1, surviving bacteria were 14% +/- 1% for PAV/PAV, 80% +/- 5% for PAV/AVI, and 70% +/- 5% for AVI/AVI

Note: The clearest published case in which a candidate natural ligand for an extra-oral TAS2R is not a food-derived bitter compound but a bacterial signaling molecule. The authors point to the possibility that T2R38 has multiple binding sites, and do not claim that AHL is its only ligand.

Verbatim: "Cultures were stimulated with the gram-negative quorum-sensing molecule N-butyryl-L-homoserine lactone (C4HSL) at 200 uM, or N-3-oxo-dodecanoyl-L-homoserine lactone (C12HSL) at 100 uM." Bacterial killing was genotype-dependent. Verbatim: "Percentage of green (viable) PAO1 after exposure to saline (no epithelial cells; negative control; 97% +/- 2%), colistin (no epithelial cells; positive control; 4% +/- 2%), PAV/PAV cultures (14% +/- 1%), PAV/AVI cultures (80% +/- 5%), AVI/AVI cultures (70% +/- 5%)." Killing required nitric oxide, and was blocked by L-NAME pretreatment or by adding cPTIO.

Limitations: An in vitro human primary culture; the authors state that T2R38 may have multiple binding sites, and do not claim that AHL is its only ligand.

Source: T2R38 taste receptor polymorphisms underlie susceptibility to upper respiratory infection (Lee RJ; Xiong G; Kofonow JM; Chen B; Lysenko A; Jiang P; Abraham V; Doghramji L; Adappa ND; Palmer JN; Kennedy DW; Beauchamp GK; Doulias PT; Ischiropoulos H; Kreindler JL; Reed DR; Cohen NA, 2012) · full text checked

Context: Connects Lee 2012's in vitro genotype-dependent defense result to a clinical outcome. Among 123 patients with chronic sinusitis (82 with nasal polyps, 41 without), TAS2R38 genotype correlated with surgical outcome only in the group without polyps: PAV/PAV homozygotes (n = 7) improved by a mean of 38 +/- 21 points on the SNOT-22, versus 12 +/- 22 points for heterozygotes and non-functional homozygotes (n = 34) (p = 0.006). In a multivariate regression incorporating scores at 1 month and 3 months (n = 207), the mean improvement for PAV/PAV patients without polyps was 20 points greater (95% CI 8 to 32; p = 0.001). Among patients with nasal polyps, mean improvement was roughly the same across genotype groups.

Limitations: An observational outcomes study, not a test of the acyl-homoserine-lactone mechanism itself, so it cannot show that AHL sensing is the causal link. The decisive subgroup is small (7 of 41 patients without polyps were PAV/PAV), and the authors list sample size, follow-up duration, unmeasured sinus microbiology, and variation in surgical technique between operators as limitations. No effect was found in the larger group of patients with polyps.

Source: TAS2R38 genotype predicts surgical outcome in nonpolypoid chronic rhinosinusitis (Adappa ND; Farquhar D; Palmer JN; Kennedy DW; Doghramji L; Morris SA; Owens D; Mansfield C; Lysenko A; Lee RJ; Cowart BJ; Reed DR; Cohen NA, 2015) · full text checked

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receptor-tas2r38 —is_activated_by→ "Bacterial acyl-homoserine lactone quorum-sensing molecules (C4HSL 200 uM, C12HSL 100 uM) in the human sinonasal epithelium. Drives calcium-dependent nitric oxide production, an increase in ciliary beat frequency, and direct bacterial killing"

claim: clm-tas2r38-sinonasal-ahl-defense / type: mechanism / updated: 2026-08-30

TAS2R38 is associated with Gram-negative bacterial infection of the paranasal sinuses: among patients carrying gram-negative bacteria in the paranasal sinuses, no homozygotes for the functional PAV/PAV form of TAS2R38 were found (chi-square test, P < 0.0058).preliminary

Scope: Retrospective genotyping of sinonasal surgery patients from a single hospital, with genotypes matched to bacterial culture results from the paranasal sinuses.

Verbatim: Among the patients with sinonasal gram-negative bacteria, none were homozygous for the functional (PAV/PAV) form of TAS2R38 (P < 0.0058 by chi2 analysis); the results were also significant when patients with no growth were compared with patients with P. aeruginosa cultures (P < 0.029).

Limitations: Retrospective and correlational. The total patient number n was not shown in the cited text and could not be extracted here. The authors state that prospective research is needed to establish causality.

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receptor-tas2r38 —is_associated_with→ "Gram-negative bacterial infection of the paranasal sinuses: among patients carrying gram-negative bacteria in the paranasal sinuses, no homozygotes for the functional PAV/PAV form of TAS2R38 were found (chi-square test, P < 0.0058)."

claim: clm-tas2r38-genotype-sinonasal-infection / type: mechanism / updated: 2026-08-30

TAS2R38 is associated with Postoperative improvement in chronic rhinosinusitis (non-polypous): PAV/PAV patients showed a SNOT-22 improvement of 38±21 versus 12±22 in non-PAV/PAV patients (p=0.006, n=41).preliminary

Scope: A prospective observational study from a single hospital. This is a clinical outcome separate from mechanistic claims.

Note: Not medical advice; genotype-outcome association record.

SNOT-22 improvement after surgery for non-polypous CRS was significantly larger in PAV/PAV subjects (38±21 vs 12±22, p=0.006, n=41).

Limitations: Single site, small sample. The causal mechanism is not established.

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receptor-tas2r38 —is_associated_with→ "Postoperative improvement in chronic rhinosinusitis (non-polypous): PAV/PAV patients showed a SNOT-22 improvement of 38±21 versus 12±22 in non-PAV/PAV patients (p=0.006, n=41)."

claim: clm-tas2r38-crs-surgical-outcome / type: mechanism / updated: 2026-08-30

goitrin activates TAS2R38preliminary

Scope: Layer: cell. Comparison of EC50 values for goitrin, PROP, and PTC by TAS2R38 functional expression assay. Part of a study examining the relationship to taste-threshold responses in 50 subjects.

"goitrin elicits a weaker response from the sensitive (PAV) allele of TAS2R38 (EC(50) = 65.0 microM) than do either PROP (EC(50) = 2.1 microM) or PTC (EC(50) = 1.1 microM) and no response at all from the insensitive (AVI) allele."

Limitations: Confirmed at abstract level. Details of assay methodology (detection method, etc.) are not described in the abstract.

Source: Genetics and bitter taste responses to goitrin, a plant toxin found in vegetables (Wooding S; Gunn H; Ramos P; Thalmann S; Xing C; Meyerhof W, 2010) · abstract checked

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compound-goitrin —activates→ receptor-tas2r38

claim: clm-w71a1-goitrin-tas2r38-pav-ec50 / type: mechanism / updated: 2026-09-07

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TAS2R38

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