{"gene":"TAS2R60","run_date":"2026-04-28T21:42:58","timeline":{"discoveries":[{"year":2013,"finding":"TAS2R60 remains an orphan bitter taste receptor with no identified agonist among 106 tested bitter compounds, suggesting it is highly selective for bitter substances not present in the tested library; the failure to identify agonists was not explained by the use of non-functional receptor variants.","method":"Heterologous expression of major haplotype variants in functional cell-based assay, challenged with 106 bitter compounds","journal":"Biochemical and biophysical research communications","confidence":"Medium","confidence_rationale":"Tier 2 — functional receptor assay with multiple haplotypes and large compound panel, single study","pmids":["23632330"],"is_preprint":false},{"year":2012,"finding":"Genetic variation within TAS2R60 is associated with individual differences in bitter taste perception (ratings of basil), indicating TAS2R60 encodes a functionally relevant bitter taste receptor in humans.","method":"Genotype-phenotype association analysis in adult twins with SNP genotyping of TAS2R60","journal":"Chemical senses","confidence":"Low","confidence_rationale":"Tier 3 — association study, no direct receptor-level mechanistic assay","pmids":["22977065"],"is_preprint":false},{"year":2017,"finding":"Genetic variation in TAS2R60 is associated with individual differences in bitterness and irritation ratings of the HIV drug lopinavir/ritonavir (Kaletra), implicating TAS2R60 in mediating bitter perception of this drug formulation.","method":"Genotype-phenotype analysis in a sensory panel of genotyped adults using generalized labeled magnitude scales","journal":"Clinical therapeutics","confidence":"Low","confidence_rationale":"Tier 3 — association-based genotype-phenotype, no direct receptor activation assay","pmids":["28923290"],"is_preprint":false},{"year":2018,"finding":"TAS2R60 mRNA is expressed in human skin, with expression levels varying by body site (sun exposure), sex, and age, indicating extraoral expression of this bitter taste receptor.","method":"Gene-specific mRNA measurement in freshly biopsied and GTEx autopsy skin samples","journal":"PloS one","confidence":"Low","confidence_rationale":"Tier 3 — mRNA expression/localization data without functional consequence established","pmids":["30332676"],"is_preprint":false}],"current_model":"TAS2R60 is a human bitter taste receptor that remains pharmacologically orphaned (no agonist identified among 106 tested compounds), is expressed in both taste and skin tissues, and shows genotype-dependent variation in bitter taste perception, but its direct ligand, signaling mechanism, and downstream pathway remain uncharacterized."},"narrative":{"teleology":[{"year":2012,"claim":"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","pmids":["22977065"],"confidence":"Low","gaps":["Association study without direct receptor activation assay; causality not established","No ligand identified for TAS2R60","Mechanism by which TAS2R60 variants alter perception is unknown"]},{"year":2013,"claim":"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","pmids":["23632330"],"confidence":"Medium","gaps":["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"]},{"year":2017,"claim":"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","pmids":["28923290"],"confidence":"Low","gaps":["Association-based; no direct demonstration that lopinavir activates TAS2R60","Irritation component may involve non-gustatory pathways","Not independently replicated"]},{"year":2018,"claim":"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","pmids":["30332676"],"confidence":"Low","gaps":["Protein-level expression in skin not confirmed","Functional role of TAS2R60 in skin is entirely unknown","Signaling partners in non-gustatory tissues not identified"]},{"year":null,"claim":"TAS2R60 remains an orphan receptor: its cognate bitter ligand(s), activation mechanism, downstream signaling effectors, and physiological role in extraoral tissues are all uncharacterized.","evidence":"","pmids":[],"confidence":"High","gaps":["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"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,1,2]}],"localization":[{"term_id":"GO:0005886","term_label":"plasma membrane","supporting_discovery_ids":[0]}],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]},"mechanistic_narrative":"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]."},"prefetch_data":{"uniprot":{"accession":"P59551","full_name":"Taste receptor type 2 member 60","aliases":["Taste receptor type 2 member 56","T2R56"],"length_aa":318,"mass_kda":36.3,"function":"Receptor that may play a role in the perception of bitterness and is gustducin-linked. May play a role in sensing the chemical composition of the gastrointestinal content. The activity of this receptor may stimulate alpha gustducin, mediate PLC-beta-2 activation and lead to the gating of TRPM5 (By similarity)","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/P59551/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TAS2R60","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/TAS2R60","total_profiled":1310},"omim":[{"mim_id":"613968","title":"TASTE RECEPTOR, TYPE 2, MEMBER 60; TAS2R60","url":"https://www.omim.org/entry/613968"},{"mim_id":"613965","title":"TASTE RECEPTOR, TYPE 2, MEMBER 41; TAS2R41","url":"https://www.omim.org/entry/613965"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Not detected","tissue_distribution":"Not detected","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAS2R60"},"hgnc":{"alias_symbol":["T2R60"],"prev_symbol":[]},"alphafold":{"accession":"P59551","domains":[{"cath_id":"1.20.1070.10","chopping":"10-302","consensus_level":"high","plddt":80.9324,"start":10,"end":302}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/P59551","model_url":"https://alphafold.ebi.ac.uk/files/AF-P59551-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-P59551-F1-predicted_aligned_error_v6.png","plddt_mean":77.88},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAS2R60","jax_strain_url":"https://www.jax.org/strain/search?query=TAS2R60"},"sequence":{"accession":"P59551","fasta_url":"https://rest.uniprot.org/uniprotkb/P59551.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/P59551/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/P59551"}},"corpus_meta":[{"pmid":"22977065","id":"PMC_22977065","title":"Genetic analysis of chemosensory traits in human twins.","date":"2012","source":"Chemical senses","url":"https://pubmed.ncbi.nlm.nih.gov/22977065","citation_count":66,"is_preprint":false},{"pmid":"23632330","id":"PMC_23632330","title":"Major haplotypes of the human bitter taste receptor TAS2R41 encode functional receptors for chloramphenicol.","date":"2013","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/23632330","citation_count":52,"is_preprint":false},{"pmid":"30332676","id":"PMC_30332676","title":"Personalized expression of bitter 'taste' receptors in human skin.","date":"2018","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/30332676","citation_count":45,"is_preprint":false},{"pmid":"28923290","id":"PMC_28923290","title":"Use of Adult Sensory Panel to Study Individual Differences in the Palatability of a Pediatric HIV Treatment Drug.","date":"2017","source":"Clinical therapeutics","url":"https://pubmed.ncbi.nlm.nih.gov/28923290","citation_count":11,"is_preprint":false},{"pmid":"39284855","id":"PMC_39284855","title":"Genomic study of taste perception genes in African Americans reveals SNPs linked to Alzheimer's disease.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/39284855","citation_count":4,"is_preprint":false},{"pmid":"39372803","id":"PMC_39372803","title":"Genomic Study of Taste Perception Genes in African Americans Reveals SNPs Linked to Alzheimer's Disease.","date":"2024","source":"bioRxiv : the preprint server for biology","url":"https://pubmed.ncbi.nlm.nih.gov/39372803","citation_count":0,"is_preprint":false},{"pmid":null,"id":"bio_10.1101_2024.08.10.607452","title":"Genomic Study of Taste Perception Genes in African Americans Reveals SNPs Linked to Alzheimer’s Disease","date":"2024-08-10","source":"bioRxiv","url":"https://doi.org/10.1101/2024.08.10.607452","citation_count":0,"is_preprint":true}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":5334,"output_tokens":786,"usd":0.013896},"stage2":{"model":"claude-opus-4-6","input_tokens":3986,"output_tokens":2505,"usd":0.123832},"total_usd":0.137728,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2013,\n      \"finding\": \"TAS2R60 remains an orphan bitter taste receptor with no identified agonist among 106 tested bitter compounds, suggesting it is highly selective for bitter substances not present in the tested library; the failure to identify agonists was not explained by the use of non-functional receptor variants.\",\n      \"method\": \"Heterologous expression of major haplotype variants in functional cell-based assay, challenged with 106 bitter compounds\",\n      \"journal\": \"Biochemical and biophysical research communications\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — functional receptor assay with multiple haplotypes and large compound panel, single study\",\n      \"pmids\": [\"23632330\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Genetic variation within TAS2R60 is associated with individual differences in bitter taste perception (ratings of basil), indicating TAS2R60 encodes a functionally relevant bitter taste receptor in humans.\",\n      \"method\": \"Genotype-phenotype association analysis in adult twins with SNP genotyping of TAS2R60\",\n      \"journal\": \"Chemical senses\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — association study, no direct receptor-level mechanistic assay\",\n      \"pmids\": [\"22977065\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2017,\n      \"finding\": \"Genetic variation in TAS2R60 is associated with individual differences in bitterness and irritation ratings of the HIV drug lopinavir/ritonavir (Kaletra), implicating TAS2R60 in mediating bitter perception of this drug formulation.\",\n      \"method\": \"Genotype-phenotype analysis in a sensory panel of genotyped adults using generalized labeled magnitude scales\",\n      \"journal\": \"Clinical therapeutics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — association-based genotype-phenotype, no direct receptor activation assay\",\n      \"pmids\": [\"28923290\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2018,\n      \"finding\": \"TAS2R60 mRNA is expressed in human skin, with expression levels varying by body site (sun exposure), sex, and age, indicating extraoral expression of this bitter taste receptor.\",\n      \"method\": \"Gene-specific mRNA measurement in freshly biopsied and GTEx autopsy skin samples\",\n      \"journal\": \"PloS one\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — mRNA expression/localization data without functional consequence established\",\n      \"pmids\": [\"30332676\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAS2R60 is a human bitter taste receptor that remains pharmacologically orphaned (no agonist identified among 106 tested compounds), is expressed in both taste and skin tissues, and shows genotype-dependent variation in bitter taste perception, but its direct ligand, signaling mechanism, and downstream pathway remain uncharacterized.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"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].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"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.\",\n      \"evidence\": \"Genotype-phenotype association in adult twins with SNP genotyping of TAS2R60 and sensory ratings of basil\",\n      \"pmids\": [\"22977065\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Association study without direct receptor activation assay; causality not established\",\n        \"No ligand identified for TAS2R60\",\n        \"Mechanism by which TAS2R60 variants alter perception is unknown\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"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.\",\n      \"evidence\": \"Heterologous expression of major haplotype variants in calcium-mobilization cell-based assay with 106 bitter compounds\",\n      \"pmids\": [\"23632330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The cognate agonist(s) remain unidentified\",\n        \"Downstream signaling pathway not directly characterized for TAS2R60\",\n        \"Only one assay format used; alternative readouts could reveal low-efficacy agonists\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"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.\",\n      \"evidence\": \"Genotype-phenotype analysis in genotyped sensory panel using generalized labeled magnitude scales for Kaletra\",\n      \"pmids\": [\"28923290\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Association-based; no direct demonstration that lopinavir activates TAS2R60\",\n        \"Irritation component may involve non-gustatory pathways\",\n        \"Not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"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.\",\n      \"evidence\": \"Gene-specific mRNA quantification in freshly biopsied and GTEx autopsy skin samples\",\n      \"pmids\": [\"30332676\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Protein-level expression in skin not confirmed\",\n        \"Functional role of TAS2R60 in skin is entirely unknown\",\n        \"Signaling partners in non-gustatory tissues not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"TAS2R60 remains an orphan receptor: its cognate bitter ligand(s), activation mechanism, downstream signaling effectors, and physiological role in extraoral tissues are all uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No agonist identified despite screening of 106 compounds\",\n        \"No structural or mutagenesis data to define the ligand-binding pocket\",\n        \"Functional consequence of extraoral expression is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 1, 2]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"GO:0009709957\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```\n\nWait, I need to fix the pathway term_id. Let me correct:\n\n```json\n{\n  \"mechanistic_narrative\": \"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].\",\n  \"teleology\": [\n    {\n      \"year\": 2012,\n      \"claim\": \"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.\",\n      \"evidence\": \"Genotype-phenotype association in adult twins with SNP genotyping of TAS2R60 and sensory ratings of basil\",\n      \"pmids\": [\"22977065\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Association study without direct receptor activation assay; causality not established\",\n        \"No ligand identified for TAS2R60\",\n        \"Mechanism by which TAS2R60 variants alter perception is unknown\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"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.\",\n      \"evidence\": \"Heterologous expression of major haplotype variants in calcium-mobilization cell-based assay with 106 bitter compounds\",\n      \"pmids\": [\"23632330\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The cognate agonist(s) remain unidentified\",\n        \"Downstream signaling pathway not directly characterized for TAS2R60\",\n        \"Only one assay format used; alternative readouts could reveal low-efficacy agonists\"\n      ]\n    },\n    {\n      \"year\": 2017,\n      \"claim\": \"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.\",\n      \"evidence\": \"Genotype-phenotype analysis in genotyped sensory panel using generalized labeled magnitude scales for Kaletra\",\n      \"pmids\": [\"28923290\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Association-based; no direct demonstration that lopinavir activates TAS2R60\",\n        \"Irritation component may involve non-gustatory pathways\",\n        \"Not independently replicated\"\n      ]\n    },\n    {\n      \"year\": 2018,\n      \"claim\": \"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.\",\n      \"evidence\": \"Gene-specific mRNA quantification in freshly biopsied and GTEx autopsy skin samples\",\n      \"pmids\": [\"30332676\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"Protein-level expression in skin not confirmed\",\n        \"Functional role of TAS2R60 in skin is entirely unknown\",\n        \"Signaling partners in non-gustatory tissues not identified\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"TAS2R60 remains an orphan receptor: its cognate bitter ligand(s), activation mechanism, downstream signaling effectors, and physiological role in extraoral tissues are all uncharacterized.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"No agonist identified despite screening of 106 compounds\",\n        \"No structural or mutagenesis data to define the ligand-binding pocket\",\n        \"Functional consequence of extraoral expression is unknown\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005886\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-9709957\", \"supporting_discovery_ids\": [1, 2]}\n    ],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}\n```"}