Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTX5MM36)

DOT Name Taste receptor type 2 member 38 (TAS2R38)
Synonyms T2R38; PTC bitter taste receptor; Taste receptor type 2 member 61; T2R61
Gene Name TAS2R38
Related Disease
Alcohol use disorder ( )
Benign neoplasm ( )
Cardiovascular disease ( )
Chromosomal disorder ( )
Craniosynostosis ( )
Cystic fibrosis ( )
Dental caries ( )
Duchenne muscular dystrophy ( )
Epilepsy ( )
Epithelial ovarian cancer ( )
Estrogen-receptor positive breast cancer ( )
Gastric cancer ( )
Goiter ( )
Graves disease ( )
Hashimoto thyroiditis ( )
High blood pressure ( )
Medullary thyroid gland carcinoma ( )
Medulloblastoma ( )
Multinodular goiter ( )
Nicotine dependence ( )
Pancreatic adenocarcinoma ( )
Parkinson disease ( )
Polyp ( )
Schizophrenia ( )
Squamous cell carcinoma ( )
Stomach cancer ( )
Thyroid cancer ( )
Thyroid gland carcinoma ( )
Thyroid tumor ( )
Advanced cancer ( )
Bacterial infection ( )
Cutaneous melanoma ( )
Lung cancer ( )
Lung carcinoma ( )
Melanoma ( )
Retinopathy ( )
Adenoma ( )
Adult glioblastoma ( )
Breast cancer ( )
Breast carcinoma ( )
Carcinoma ( )
Colorectal adenoma ( )
Glioblastoma multiforme ( )
Hepatocellular carcinoma ( )
Obesity ( )
Plasma cell myeloma ( )
UniProt ID
T2R38_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF05296
Sequence
MLTLTRIRTVSYEVRSTFLFISVLEFAVGFLTNAFVFLVNFWDVVKRQALSNSDCVLLCL
SISRLFLHGLLFLSAIQLTHFQKLSEPLNHSYQAIIMLWMIANQANLWLAACLSLLYCSK
LIRFSHTFLICLASWVSRKISQMLLGIILCSCICTVLCVWCFFSRPHFTVTTVLFMNNNT
RLNWQIKDLNLFYSFLFCYLWSVPPFLLFLVSSGMLTVSLGRHMRTMKVYTRNSRDPSLE
AHIKALKSLVSFFCFFVISSCAAFISVPLLILWRDKIGVMVCVGIMAACPSGHAAILISG
NAKLRRAVMTILLWAQSSLKVRADHKADSRTLC
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.
Tissue Specificity Expressed in subsets of taste receptor cells of the tongue and exclusively in gustducin-positive cells. Expressed in testis .
KEGG Pathway
Taste transduction (hsa04742 )
Reactome Pathway
Class C/3 (Metabotropic glutamate/pheromone receptors) (R-HSA-420499 )
Sensory perception of sweet, bitter, and umami (glutamate) taste (R-HSA-9717207 )
G alpha (i) signalling events (R-HSA-418594 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alcohol use disorder DISMB65Y Strong Biomarker [1]
Benign neoplasm DISDUXAD Strong Biomarker [2]
Cardiovascular disease DIS2IQDX Strong Genetic Variation [3]
Chromosomal disorder DISM5BB5 Strong Genetic Variation [4]
Craniosynostosis DIS6J405 Strong Biomarker [5]
Cystic fibrosis DIS2OK1Q Strong Altered Expression [6]
Dental caries DISRBCMD Strong Genetic Variation [7]
Duchenne muscular dystrophy DISRQ3NV Strong Biomarker [8]
Epilepsy DISBB28L Strong Genetic Variation [9]
Epithelial ovarian cancer DIS56MH2 Strong Biomarker [10]
Estrogen-receptor positive breast cancer DIS1H502 Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Genetic Variation [12]
Goiter DISLCGI6 Strong Biomarker [13]
Graves disease DISU4KOQ Strong Biomarker [14]
Hashimoto thyroiditis DIS77CDF Strong Genetic Variation [15]
High blood pressure DISY2OHH Strong Genetic Variation [16]
Medullary thyroid gland carcinoma DISHBL3K Strong Biomarker [17]
Medulloblastoma DISZD2ZL Strong Genetic Variation [18]
Multinodular goiter DISZQJH7 Strong Genetic Variation [19]
Nicotine dependence DISZD9W7 Strong Biomarker [20]
Pancreatic adenocarcinoma DISKHX7S Strong Biomarker [21]
Parkinson disease DISQVHKL Strong Genetic Variation [22]
Polyp DISRSLYF Strong Genetic Variation [23]
Schizophrenia DISSRV2N Strong Genetic Variation [24]
Squamous cell carcinoma DISQVIFL Strong Biomarker [25]
Stomach cancer DISKIJSX Strong Genetic Variation [12]
Thyroid cancer DIS3VLDH Strong Genetic Variation [26]
Thyroid gland carcinoma DISMNGZ0 Strong Genetic Variation [27]
Thyroid tumor DISLVKMD Strong Genetic Variation [26]
Advanced cancer DISAT1Z9 moderate Biomarker [28]
Bacterial infection DIS5QJ9S moderate Genetic Variation [29]
Cutaneous melanoma DIS3MMH9 moderate Genetic Variation [30]
Lung cancer DISCM4YA moderate Altered Expression [31]
Lung carcinoma DISTR26C moderate Altered Expression [31]
Melanoma DIS1RRCY moderate Genetic Variation [30]
Retinopathy DISB4B0F moderate Biomarker [32]
Adenoma DIS78ZEV Limited Biomarker [33]
Adult glioblastoma DISVP4LU Limited Biomarker [34]
Breast cancer DIS7DPX1 Limited Biomarker [35]
Breast carcinoma DIS2UE88 Limited Biomarker [35]
Carcinoma DISH9F1N Limited Altered Expression [36]
Colorectal adenoma DISTSVHM Limited Genetic Variation [37]
Glioblastoma multiforme DISK8246 Limited Biomarker [34]
Hepatocellular carcinoma DIS0J828 Limited Biomarker [38]
Obesity DIS47Y1K Limited Biomarker [39]
Plasma cell myeloma DIS0DFZ0 Limited Biomarker [40]
------------------------------------------------------------------------------------
⏷ Show the Full List of 46 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
4 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Propylthiouracil DM6D7N8 Approved Propylthiouracil increases the activity of Taste receptor type 2 member 38 (TAS2R38). [41]
Probenecid DMMFWOJ Approved Probenecid decreases the activity of Taste receptor type 2 member 38 (TAS2R38). [41]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Taste receptor type 2 member 38 (TAS2R38). [43]
PHENYLTHIOUREA DMM1IAU Investigative PHENYLTHIOUREA increases the activity of Taste receptor type 2 member 38 (TAS2R38). [41]
------------------------------------------------------------------------------------
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Taste receptor type 2 member 38 (TAS2R38). [42]
------------------------------------------------------------------------------------

References

1 Functional variants in TAS2R38 and TAS2R16 influence alcohol consumption in high-risk families of African-American origin.Alcohol Clin Exp Res. 2007 Feb;31(2):209-15. doi: 10.1111/j.1530-0277.2006.00297.x.
2 Noninvasive Follicular Variant of Papillary Thyroid Carcinoma and the Afirma Gene-Expression Classifier.Thyroid. 2016 Jul;26(7):911-5. doi: 10.1089/thy.2015.0644.
3 Bitter receptor gene (TAS2R38) P49A genotypes and their associations with aversion to vegetables and sweet/fat foods in Malaysian subjects.Asia Pac J Clin Nutr. 2010;19(4):491-8.
4 Follicular variant of papillary thyroid carcinoma: genome-wide appraisal of a controversial entity.Genes Chromosomes Cancer. 2004 Aug;40(4):355-64. doi: 10.1002/gcc.20049.
5 The Role of Quinine-Responsive Taste Receptor Family 2 in Airway Immune Defense and Chronic Rhinosinusitis.Front Immunol. 2018 Mar 28;9:624. doi: 10.3389/fimmu.2018.00624. eCollection 2018.
6 T2R38 genotype is correlated with sinonasal quality of life in homozygous F508 cystic fibrosis patients.Int Forum Allergy Rhinol. 2016 Apr;6(4):356-61. doi: 10.1002/alr.21675. Epub 2015 Dec 17.
7 Gene-environment Interactions in the Etiology of Dental Caries.J Dent Res. 2016 Jan;95(1):74-9. doi: 10.1177/0022034515605281. Epub 2015 Sep 16.
8 The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States.J Manag Care Spec Pharm. 2017 Jun;23(6):633-641. doi: 10.18553/jmcp.2017.23.6.633.
9 Genetic epidemiology of epilepsy: a twin study.Neurol India. 2005 Mar;53(1):93-8. doi: 10.4103/0028-3886.15070.
10 Evaluating the Mechanism and Therapeutic Potential of PTC-028, a Novel Inhibitor of BMI-1 Function in Ovarian Cancer.Mol Cancer Ther. 2018 Jan;17(1):39-49. doi: 10.1158/1535-7163.MCT-17-0574. Epub 2017 Nov 20.
11 The rearranged during transfection/papillary thyroid carcinoma tyrosine kinase is an estrogen-dependent gene required for the growth of estrogen receptor positive breast cancer cells.Breast Cancer Res Treat. 2012 Jun;133(2):487-500. doi: 10.1007/s10549-011-1775-9. Epub 2011 Sep 24.
12 Genetic Variation in the TAS2R38 Bitter Taste Receptor and Gastric Cancer Risk in Koreans.Sci Rep. 2016 Jun 1;6:26904. doi: 10.1038/srep26904.
13 Circulating ctDNA methylation quantification of two DNA methyl transferases in papillary thyroid carcinoma.J Cell Biochem. 2019 Oct;120(10):17422-17437. doi: 10.1002/jcb.29007. Epub 2019 May 24.
14 INSL-3 is expressed in human hyperplastic and neoplastic thyrocytes.Int J Oncol. 2003 May;22(5):993-1001.
15 Upregulation Of Protein Tyrosine Phosphatase Receptor Type C Associates To The Combination Of Hashimoto's Thyroiditis And Papillary Thyroid Carcinoma And Is Predictive Of A Poor Prognosis.Onco Targets Ther. 2019 Oct 14;12:8479-8489. doi: 10.2147/OTT.S226426. eCollection 2019.
16 Prevalence of common disease-associated variants in Asian Indians.BMC Genet. 2008 Feb 4;9:13. doi: 10.1186/1471-2156-9-13.
17 Multiple HABP2 variants in familial papillary thyroid carcinoma: Contribution of a group of "thyroid-checked" controls.Eur J Med Genet. 2017 Mar;60(3):178-184. doi: 10.1016/j.ejmg.2017.01.001. Epub 2017 Jan 9.
18 Genetics of brain tumors.Curr Opin Pediatr. 2000 Dec;12(6):543-8. doi: 10.1097/00008480-200012000-00005.
19 Molecular Testing for Oncogenic Gene Alterations in Pediatric Thyroid Lesions.Thyroid. 2018 Jan;28(1):60-67. doi: 10.1089/thy.2017.0059. Epub 2017 Dec 11.
20 A combinatorial approach to detecting gene-gene and gene-environment interactions in family studies.Am J Hum Genet. 2008 Oct;83(4):457-67. doi: 10.1016/j.ajhg.2008.09.001. Epub 2008 Oct 2.
21 Cytological evaluation by fine needle aspiration biopsy of incidental focal increased fluorodeoxyglucose uptake in thyroid on positron emission tomography scan.Diagn Cytopathol. 2017 Jun;45(6):501-506. doi: 10.1002/dc.23695. Epub 2017 Mar 6.
22 6-n-propylthiouracil taste disruption and TAS2R38 nontasting form in Parkinson's disease.Mov Disord. 2018 Aug;33(8):1331-1339. doi: 10.1002/mds.27391. Epub 2018 Mar 24.
23 Impact of bitter taste receptor phenotype upon clinical presentation in chronic rhinosinusitis.Int Forum Allergy Rhinol. 2018 Sep;8(9):1013-1020. doi: 10.1002/alr.22138. Epub 2018 Jul 4.
24 Association of schizophrenia with the phenylthiocarbamide taste receptor haplotype on chromosome 7q.Psychiatr Genet. 2012 Dec;22(6):286-9. doi: 10.1097/YPG.0b013e32835863f0.
25 Pharmacological inhibition of Bmi1 by PTC-209 impaired tumor growth in head neck squamous cell carcinoma.Cancer Cell Int. 2017 Nov 21;17:107. doi: 10.1186/s12935-017-0481-z. eCollection 2017.
26 Selected single-nucleotide polymorphisms in FOXE1, SERPINA5, FTO, EVPL, TICAM1 and SCARB1 are associated with papillary and follicular thyroid cancer risk: replication study in a German population.Carcinogenesis. 2016 Jul;37(7):677-684. doi: 10.1093/carcin/bgw047. Epub 2016 Apr 28.
27 ETV6-NTRK3 and STRN-ALK kinase fusions are recurrent events in papillary thyroid cancer of adult population.Eur J Endocrinol. 2018 Jan;178(1):83-91. doi: 10.1530/EJE-17-0499. Epub 2017 Oct 18.
28 PD-L1 and thyroid cytology: A possible diagnostic and prognostic marker.Cancer Cytopathol. 2020 Mar;128(3):177-189. doi: 10.1002/cncy.22224. Epub 2019 Dec 10.
29 In Vivo Biofilm Formation, Gram-Negative Infections and TAS2R38 Polymorphisms in CRSw NP Patients.Laryngoscope. 2018 Oct;128(10):E339-E345. doi: 10.1002/lary.27175. Epub 2018 Mar 23.
30 Synchronous occurrence of medullary and papillary carcinoma of the thyroid in a patient with cutaneous melanoma: determination of BRAFV600E in peripheral blood and tissues. Report of a case and review of the literature.Endocr Pathol. 2014 Sep;25(3):324-31. doi: 10.1007/s12022-014-9303-1.
31 Biological and clinical significance of epigenetic silencing of MARVELD1 gene in lung cancer.Sci Rep. 2014 Dec 18;4:7545. doi: 10.1038/srep07545.
32 Functional rescue of REP1 following treatment with PTC124 and novel derivative PTC-414 in human choroideremia fibroblasts and the nonsense-mediated zebrafish model.Hum Mol Genet. 2016 Aug 15;25(16):3416-3431. doi: 10.1093/hmg/ddw184. Epub 2016 Jun 21.
33 Overexpression of the S-phase kinase-associated protein 2 in thyroid cancer.Endocr Relat Cancer. 2007 Jun;14(2):405-20. doi: 10.1677/ERC-06-0030.
34 Targeting of BMI-1 with PTC-209 inhibits glioblastoma development.Cell Cycle. 2018;17(10):1199-1211. doi: 10.1080/15384101.2018.1469872. Epub 2018 Jul 23.
35 Downregulation of Bmi1 in breast cancer stem cells suppresses tumor growth and proliferation.Oncotarget. 2017 Jun 13;8(24):38731-38742. doi: 10.18632/oncotarget.16317.
36 Mutual regulation of TGF-1, TRII and ErbB receptors expression in human thyroid carcinomas.Exp Cell Res. 2014 Sep 10;327(1):24-36. doi: 10.1016/j.yexcr.2014.06.012. Epub 2014 Jun 26.
37 Variations in bitter-taste receptor genes, dietary intake, and colorectal adenoma risk.Nutr Cancer. 2013;65(7):982-90. doi: 10.1080/01635581.2013.807934. Epub 2013 Oct 1.
38 HOXA-AS2 Promotes Proliferation and Induces Epithelial-Mesenchymal Transition via the miR-520c-3p/GPC3 Axis in Hepatocellular Carcinoma.Cell Physiol Biochem. 2018;50(6):2124-2138. doi: 10.1159/000495056. Epub 2018 Nov 9.
39 Expression of the Bitter Taste Receptor, T2R38, in Enteroendocrine Cells of the Colonic Mucosa of Overweight/Obese vs. Lean Subjects.PLoS One. 2016 Feb 11;11(2):e0147468. doi: 10.1371/journal.pone.0147468. eCollection 2016.
40 The polycomb group protein BMI-1 inhibitor PTC-209 is a potent anti-myeloma agent alone or in combination with epigenetic inhibitors targeting EZH2 and the BET bromodomains.Oncotarget. 2017 Oct 20;8(61):103731-103743. doi: 10.18632/oncotarget.21909. eCollection 2017 Nov 28.
41 Probenecid inhibits the human bitter taste receptor TAS2R16 and suppresses bitter perception of salicin. PLoS One. 2011;6(5):e20123.
42 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
43 Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.