Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUBUJ2N)

• DOT Name: Trace amine-associated receptor 6 (TAAR6)
• Synonyms: TaR-6; Trace amine receptor 6; Trace amine receptor 4; TaR-4
• Gene Name: TAAR6
• Related Disease:
  Autism spectrum disorder
  Brain disease
  Depression
  Major depressive disorder
  Mood disorder
  Amyotrophic lateral sclerosis
  Asthma
• UniProt ID: TAAR6_HUMAN
• Pfam ID: PF00001
• Sequence:
  MSSNSSLLVAVQLCYANVNGSCVKIPFSPGSRVILYIVFGFGAVLAVFGNLLVMISILHF
  KQLHSPTNFLVASLACADFLVGVTVMPFSMVRTVESCWYFGRSFCTFHTCCDVAFCYSSL
  FHLCFISIDRYIAVTDPLVYPTKFTVSVSGICISVSWILPLMYSGAVFYTGVYDDGLEEL
  SDALNCIGGCQTVVNQNWVLTDFLSFFIPTFIMIILYGNIFLVARRQAKKIENTGSKTES
  SSESYKARVARRERKAAKTLGVTVVAFMISWLPYSIDSLIDAFMGFITPACIYEICCWCA
  YYNSAMNPLIYALFYPWFRKAIKVIVTGQVLKNSSATMNLFSEHI
• Function: Orphan receptor. Could be a receptor for trace amines. Trace amines are biogenic amines present in very low levels in mammalian tissues. Although some trace amines have clearly defined roles as neurotransmitters in invertebrates, the extent to which they function as true neurotransmitters in vertebrates has remained speculative. Trace amines are likely to be involved in a variety of physiological functions that have yet to be fully understood.
• Tissue Specificity: Expressed at low abundance in various brain tissues, as well as in fetal liver, but not in the cerebellum or placenta. In the brain, comparable levels of expression in basal ganglia, frontal cortex, substantia nigra, amygdala and hippocampus, highest expression in hippocampus and lowest expression in basal ganglia.
• KEGG Pathway: Neuroactive ligand-receptor interaction (hsa04080)
• Reactome Pathway:
  G alpha (s) signalling events (R-HSA-418555)
  Amine ligand-binding receptors (R-HSA-375280)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Brain disease	DIS6ZC3X	Strong	Biomarker	[2]
Depression	DIS3XJ69	Strong	Biomarker	[3]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[4]
Mood disorder	DISLVMWO	Strong	Biomarker	[5]
Amyotrophic lateral sclerosis	DISF7HVM	Limited	Biomarker	[6]
Asthma	DISW9QNS	Limited	Genetic Variation	[7]

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 affects the methylation of Trace amine-associated receptor 6 (TAAR6).	[8]

1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Trace amine-associated receptor 6 (TAAR6).	[9]

References

• [1] Peptidome Analysis Reveals Novel Serum Biomarkers for Children with Autism Spectrum Disorder in China.Proteomics Clin Appl. 2018 Sep;12(5):e1700164. doi: 10.1002/prca.201700164. Epub 2018 May 30.
• [2] Molecular Variants in Human Trace Amine-Associated Receptors and Their Implications in Mental and Metabolic Disorders.Cell Mol Neurobiol. 2020 Mar;40(2):239-255. doi: 10.1007/s10571-019-00743-y. Epub 2019 Oct 23.
• [3] TAAR6 variations possibly associated with antidepressant response and suicidal behavior.Psychiatry Res. 2010 Nov 30;180(1):20-4. doi: 10.1016/j.psychres.2009.08.007. Epub 2010 May 21.
• [4] Association of the trace amine associated receptor 6 (TAAR6) gene with schizophrenia and bipolar disorder in a Korean case control sample.J Psychiatr Res. 2008 Jan;42(1):35-40. doi: 10.1016/j.jpsychires.2006.09.011. Epub 2006 Nov 9.
• [5] Investigation of an epistastic effect between a set of TAAR6 and HSP-70 genes variations and major mood disorders.Am J Med Genet B Neuropsychiatr Genet. 2010 Mar 5;153B(2):680-683. doi: 10.1002/ajmg.b.31009.
• [6] mTh1 driven expression of hTDP-43 results in typical ALS/FTLD neuropathological symptoms.PLoS One. 2018 May 22;13(5):e0197674. doi: 10.1371/journal.pone.0197674. eCollection 2018.
• [7] Association between TAAR6 polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.Pharmacogenet Genomics. 2015 Jul;25(7):334-42. doi: 10.1097/FPC.0000000000000141.
• [8] 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.
• [9] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.