{"gene":"TAS2R13","run_date":"2026-06-10T10:51:54","timeline":{"discoveries":[{"year":2023,"finding":"Lopinavir activates TAS2R13 (and TAS2R1), while ritonavir activates TAS2R13 (and TAS2R1, TAS2R8, TAS2R14), as determined by calcium mobilization assay in cells expressing these receptors.","method":"Calcium mobilization assay in receptor-expressing cells","journal":"Chemical senses","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional cell-based assay establishing agonist activation, single lab, single method","pmids":["37625013"],"is_preprint":false},{"year":2023,"finding":"Theasinensin A binds to a half-open cavity at the N-terminal of TAS2R13 (as well as TAS2R14 and TAS2R16), with hydrogen bond and hydrophobic interactions contributing to differential bitterness receptor activation; TAS2R16 showed the highest affinity among the three receptors tested.","method":"Molecular docking / in silico binding affinity analysis","journal":"Frontiers in nutrition","confidence":"Low","confidence_rationale":"Tier 4 / Weak — computational docking only, no experimental functional validation of TAS2R13 binding reported","pmids":["37229471"],"is_preprint":false},{"year":2023,"finding":"Morus alba leaf extract inhibits TAS2R13 (and TAS2R3) bitter taste receptor activity, as measured by calcium release assay in transfected HEK293T cells.","method":"Calcium release assay in transfected HEK293T cells","journal":"Plant foods for human nutrition","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — functional cell-based assay in transfected cells, single lab, single method","pmids":["37796414"],"is_preprint":false},{"year":2024,"finding":"Selected phenolic acids and flavonoids from Cornelian cherry (including naringin and quercetin) inhibit TAS2R13 receptor activity; binding affinity and interaction mechanisms with TAS2R13 varied among compounds, with naringin and quercetin showing binding affinity most similar to model agonists chloroquine and denatonium, validated by in vitro functional assays in receptor-expressing cells.","method":"Molecular docking combined with in vitro functional assay (calcium-based inhibition assay in receptor-expressing cells)","journal":"Scientific reports","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — two orthogonal methods (docking + functional cell assay) but single lab","pmids":["38987427"],"is_preprint":false}],"current_model":"TAS2R13 is a functional bitter taste receptor that can be activated by diverse ligands including lopinavir and ritonavir (anti-HIV drugs), and inhibited by plant-derived phenolics such as Morus alba extracts and Cornelian cherry flavonoids; ligand binding occurs at a half-open cavity at the receptor's N-terminal domain involving hydrogen bond and hydrophobic interactions, as established by calcium mobilization assays in transfected cells and molecular docking studies."},"narrative":{"mechanistic_narrative":"TAS2R13 is a functional bitter taste receptor that responds to structurally diverse agonists and is subject to inhibition by plant-derived phenolics. It is activated by the anti-HIV protease inhibitors lopinavir and ritonavir, as shown by calcium mobilization in receptor-expressing cells [PMID:37625013]. Its activity is inhibited by Morus alba leaf extract [PMID:37796414] and by phenolic acids and flavonoids from Cornelian cherry, including naringin and quercetin, with these compounds engaging the receptor in a manner comparable to model agonists [PMID:38987427]. Ligand recognition occurs at a half-open cavity at the receptor's N-terminal region, mediated by hydrogen-bond and hydrophobic interactions [PMID:37229471]. Beyond ligand activation and inhibition characterized through cell-based calcium assays and docking, no downstream signaling partners or structural model have been characterized in the available corpus.","teleology":[{"year":2023,"claim":"Establishing that TAS2R13 is a functional receptor with identifiable agonists answered whether specific drug molecules can trigger its activity, linking bitter perception to off-target taste responses of clinical compounds.","evidence":"Calcium mobilization assay in cells expressing TAS2R13, tested with lopinavir and ritonavir","pmids":["37625013"],"confidence":"Medium","gaps":["Single lab, single functional method","Downstream G-protein coupling and signaling cascade not defined","No dose-response potency comparison across receptors reported here"]},{"year":2023,"claim":"Computational docking addressed where ligands bind on TAS2R13, locating a half-open N-terminal cavity engaged through hydrogen-bond and hydrophobic contacts.","evidence":"Molecular docking / in silico binding affinity analysis of theasinensin A against TAS2R13","pmids":["37229471"],"confidence":"Low","gaps":["Computational docking only, no experimental functional validation of theasinensin A binding to TAS2R13","No experimental structure of the receptor","Predicted cavity not confirmed by mutagenesis"]},{"year":2023,"claim":"Identifying that a plant extract suppresses TAS2R13 activity established the receptor as a target for bitterness inhibition, not only activation.","evidence":"Calcium release assay in transfected HEK293T cells with Morus alba leaf extract","pmids":["37796414"],"confidence":"Medium","gaps":["Active inhibitory constituents within the extract not isolated","Mechanism of inhibition (orthosteric vs allosteric) undefined","Single lab, single method"]},{"year":2024,"claim":"Pairing docking with functional assays identified specific flavonoids that inhibit TAS2R13 and compared their binding behavior to model agonists, refining structure-activity understanding of the receptor.","evidence":"Molecular docking combined with calcium-based inhibition functional assay in receptor-expressing cells, testing Cornelian cherry phenolics including naringin and quercetin","pmids":["38987427"],"confidence":"Medium","gaps":["Single lab","Binding poses not validated by mutagenesis or structural data","Physiological relevance of inhibition in vivo not tested"]},{"year":null,"claim":"The downstream signaling mechanism, receptor structure, and physiological role of TAS2R13 beyond ligand activation/inhibition remain undefined.","evidence":"","pmids":[],"confidence":"Low","gaps":["No experimental structure or validated binding-site residues","G-protein coupling and intracellular cascade not characterized in the corpus","In vivo taste or extra-oral physiological role not established"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060089","term_label":"molecular transducer activity","supporting_discovery_ids":[0,2,3]}],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q9NYV9","full_name":"Taste receptor type 2 member 13","aliases":["Taste receptor family B member 3","TRB3"],"length_aa":303,"mass_kda":35.1,"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","subcellular_location":"Membrane","url":"https://www.uniprot.org/uniprotkb/Q9NYV9/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TAS2R13","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/TAS2R13","total_profiled":1310},"omim":[{"mim_id":"604792","title":"TASTE RECEPTOR, TYPE 2, MEMBER 13; TAS2R13","url":"https://www.omim.org/entry/604792"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"","locations":[],"tissue_specificity":"Not detected","tissue_distribution":"Not detected","driving_tissues":[],"url":"https://www.proteinatlas.org/search/TAS2R13"},"hgnc":{"alias_symbol":["T2R13","TRB3"],"prev_symbol":[]},"alphafold":{"accession":"Q9NYV9","domains":[{"cath_id":"1.20.1070.10","chopping":"4-295","consensus_level":"medium","plddt":88.6775,"start":4,"end":295}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NYV9","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NYV9-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q9NYV9-F1-predicted_aligned_error_v6.png","plddt_mean":88.12},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TAS2R13","jax_strain_url":"https://www.jax.org/strain/search?query=TAS2R13"},"sequence":{"accession":"Q9NYV9","fasta_url":"https://rest.uniprot.org/uniprotkb/Q9NYV9.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q9NYV9/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q9NYV9"}},"corpus_meta":[{"pmid":"23656994","id":"PMC_23656994","title":"Functional genomics reveals dysregulation of cortical olfactory receptors in Parkinson disease: novel putative chemoreceptors in the human brain.","date":"2013","source":"Journal of neuropathology and experimental neurology","url":"https://pubmed.ncbi.nlm.nih.gov/23656994","citation_count":102,"is_preprint":false},{"pmid":"24415641","id":"PMC_24415641","title":"Genetic variations in taste receptors are associated with chronic rhinosinusitis: a replication study.","date":"2014","source":"International forum of allergy & rhinology","url":"https://pubmed.ncbi.nlm.nih.gov/24415641","citation_count":83,"is_preprint":false},{"pmid":"22824251","id":"PMC_22824251","title":"Variation in the gene TAS2R13 is associated with differences in alcohol consumption in patients with head and neck cancer.","date":"2012","source":"Chemical senses","url":"https://pubmed.ncbi.nlm.nih.gov/22824251","citation_count":45,"is_preprint":false},{"pmid":"23365305","id":"PMC_23365305","title":"Assessment of the presence of chemosensing receptors based on bitter and fat taste in the gastrointestinal tract of young pig.","date":"2012","source":"Journal of animal science","url":"https://pubmed.ncbi.nlm.nih.gov/23365305","citation_count":25,"is_preprint":false},{"pmid":"33821765","id":"PMC_33821765","title":"Transcriptomic profiling as biological markers of depression - A pilot study in unipolar and bipolar women.","date":"2021","source":"The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry","url":"https://pubmed.ncbi.nlm.nih.gov/33821765","citation_count":22,"is_preprint":false},{"pmid":"26635288","id":"PMC_26635288","title":"Pathway, in silico and tissue-specific expression quantitative analyses of oesophageal squamous cell carcinoma genome-wide association studies data.","date":"2015","source":"International journal of epidemiology","url":"https://pubmed.ncbi.nlm.nih.gov/26635288","citation_count":20,"is_preprint":false},{"pmid":"37229471","id":"PMC_37229471","title":"Bitterness quantification and simulated taste mechanism of theasinensin A from tea.","date":"2023","source":"Frontiers in nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/37229471","citation_count":12,"is_preprint":false},{"pmid":"23171479","id":"PMC_23171479","title":"Identification of novel genes for bitter taste receptors in sheep (Ovis aries).","date":"2012","source":"Animal : an international journal of animal bioscience","url":"https://pubmed.ncbi.nlm.nih.gov/23171479","citation_count":6,"is_preprint":false},{"pmid":"37625013","id":"PMC_37625013","title":"Anti-HIV drugs lopinavir/ritonavir activate bitter taste receptors.","date":"2023","source":"Chemical senses","url":"https://pubmed.ncbi.nlm.nih.gov/37625013","citation_count":5,"is_preprint":false},{"pmid":"37796414","id":"PMC_37796414","title":"Morus alba L. Leaves (WML) Modulate Sweet (TAS1R) and Bitter (TAS2R) Taste in the Studies on Human Receptors - A New Perspective on the Utilization of White Mulberry Leaves in Food Production?","date":"2023","source":"Plant foods for human nutrition (Dordrecht, Netherlands)","url":"https://pubmed.ncbi.nlm.nih.gov/37796414","citation_count":5,"is_preprint":false},{"pmid":"38987427","id":"PMC_38987427","title":"Docking analysis of phenolic acid and flavonoids with selected TAS2R receptors and in vitro experiment.","date":"2024","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/38987427","citation_count":2,"is_preprint":false},{"pmid":"41140001","id":"PMC_41140001","title":"Exploring the Role of TAS2Rs in Obesity: Insights From Human and Rat Models.","date":"2025","source":"Obesity (Silver Spring, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/41140001","citation_count":2,"is_preprint":false},{"pmid":"37841228","id":"PMC_37841228","title":"The evolution of bitter taste receptor gene in primates: Gene duplication and selection.","date":"2023","source":"Ecology and evolution","url":"https://pubmed.ncbi.nlm.nih.gov/37841228","citation_count":1,"is_preprint":false},{"pmid":"38892689","id":"PMC_38892689","title":"The Influence of Taste Genes on Body Fat and Alcohol Consumption.","date":"2024","source":"Nutrients","url":"https://pubmed.ncbi.nlm.nih.gov/38892689","citation_count":1,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":9020,"output_tokens":896,"usd":0.02025,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7372,"output_tokens":1509,"usd":0.037292,"stage2_stop_reason":"end_turn"},"total_usd":0.057542,"stage1_batch_id":"msgbatch_017qqVz33Ga63SCDwzb35XPb","stage2_batch_id":"msgbatch_01Scr2Ei9x4HJMiRGxwrmvLK","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2023,\n      \"finding\": \"Lopinavir activates TAS2R13 (and TAS2R1), while ritonavir activates TAS2R13 (and TAS2R1, TAS2R8, TAS2R14), as determined by calcium mobilization assay in cells expressing these receptors.\",\n      \"method\": \"Calcium mobilization assay in receptor-expressing cells\",\n      \"journal\": \"Chemical senses\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional cell-based assay establishing agonist activation, single lab, single method\",\n      \"pmids\": [\"37625013\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Theasinensin A binds to a half-open cavity at the N-terminal of TAS2R13 (as well as TAS2R14 and TAS2R16), with hydrogen bond and hydrophobic interactions contributing to differential bitterness receptor activation; TAS2R16 showed the highest affinity among the three receptors tested.\",\n      \"method\": \"Molecular docking / in silico binding affinity analysis\",\n      \"journal\": \"Frontiers in nutrition\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 4 / Weak — computational docking only, no experimental functional validation of TAS2R13 binding reported\",\n      \"pmids\": [\"37229471\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2023,\n      \"finding\": \"Morus alba leaf extract inhibits TAS2R13 (and TAS2R3) bitter taste receptor activity, as measured by calcium release assay in transfected HEK293T cells.\",\n      \"method\": \"Calcium release assay in transfected HEK293T cells\",\n      \"journal\": \"Plant foods for human nutrition\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — functional cell-based assay in transfected cells, single lab, single method\",\n      \"pmids\": [\"37796414\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2024,\n      \"finding\": \"Selected phenolic acids and flavonoids from Cornelian cherry (including naringin and quercetin) inhibit TAS2R13 receptor activity; binding affinity and interaction mechanisms with TAS2R13 varied among compounds, with naringin and quercetin showing binding affinity most similar to model agonists chloroquine and denatonium, validated by in vitro functional assays in receptor-expressing cells.\",\n      \"method\": \"Molecular docking combined with in vitro functional assay (calcium-based inhibition assay in receptor-expressing cells)\",\n      \"journal\": \"Scientific reports\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — two orthogonal methods (docking + functional cell assay) but single lab\",\n      \"pmids\": [\"38987427\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TAS2R13 is a functional bitter taste receptor that can be activated by diverse ligands including lopinavir and ritonavir (anti-HIV drugs), and inhibited by plant-derived phenolics such as Morus alba extracts and Cornelian cherry flavonoids; ligand binding occurs at a half-open cavity at the receptor's N-terminal domain involving hydrogen bond and hydrophobic interactions, as established by calcium mobilization assays in transfected cells and molecular docking studies.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"TAS2R13 is a functional bitter taste receptor that responds to structurally diverse agonists and is subject to inhibition by plant-derived phenolics. It is activated by the anti-HIV protease inhibitors lopinavir and ritonavir, as shown by calcium mobilization in receptor-expressing cells [#0]. Its activity is inhibited by Morus alba leaf extract [#2] and by phenolic acids and flavonoids from Cornelian cherry, including naringin and quercetin, with these compounds engaging the receptor in a manner comparable to model agonists [#3]. Ligand recognition occurs at a half-open cavity at the receptor's N-terminal region, mediated by hydrogen-bond and hydrophobic interactions [#1]. Beyond ligand activation and inhibition characterized through cell-based calcium assays and docking, no downstream signaling partners or structural model have been characterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 2023,\n      \"claim\": \"Establishing that TAS2R13 is a functional receptor with identifiable agonists answered whether specific drug molecules can trigger its activity, linking bitter perception to off-target taste responses of clinical compounds.\",\n      \"evidence\": \"Calcium mobilization assay in cells expressing TAS2R13, tested with lopinavir and ritonavir\",\n      \"pmids\": [\"37625013\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab, single functional method\", \"Downstream G-protein coupling and signaling cascade not defined\", \"No dose-response potency comparison across receptors reported here\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Computational docking addressed where ligands bind on TAS2R13, locating a half-open N-terminal cavity engaged through hydrogen-bond and hydrophobic contacts.\",\n      \"evidence\": \"Molecular docking / in silico binding affinity analysis of theasinensin A against TAS2R13\",\n      \"pmids\": [\"37229471\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Computational docking only, no experimental functional validation of theasinensin A binding to TAS2R13\", \"No experimental structure of the receptor\", \"Predicted cavity not confirmed by mutagenesis\"]\n    },\n    {\n      \"year\": 2023,\n      \"claim\": \"Identifying that a plant extract suppresses TAS2R13 activity established the receptor as a target for bitterness inhibition, not only activation.\",\n      \"evidence\": \"Calcium release assay in transfected HEK293T cells with Morus alba leaf extract\",\n      \"pmids\": [\"37796414\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Active inhibitory constituents within the extract not isolated\", \"Mechanism of inhibition (orthosteric vs allosteric) undefined\", \"Single lab, single method\"]\n    },\n    {\n      \"year\": 2024,\n      \"claim\": \"Pairing docking with functional assays identified specific flavonoids that inhibit TAS2R13 and compared their binding behavior to model agonists, refining structure-activity understanding of the receptor.\",\n      \"evidence\": \"Molecular docking combined with calcium-based inhibition functional assay in receptor-expressing cells, testing Cornelian cherry phenolics including naringin and quercetin\",\n      \"pmids\": [\"38987427\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"Single lab\", \"Binding poses not validated by mutagenesis or structural data\", \"Physiological relevance of inhibition in vivo not tested\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The downstream signaling mechanism, receptor structure, and physiological role of TAS2R13 beyond ligand activation/inhibition remain undefined.\",\n      \"evidence\": null,\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"No experimental structure or validated binding-site residues\", \"G-protein coupling and intracellular cascade not characterized in the corpus\", \"In vivo taste or extra-oral physiological role not established\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060089\", \"supporting_discovery_ids\": [0, 2, 3]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"win","faith_supported":3,"faith_total":3,"faith_pct":100.0}}