Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ9XNBB)

• DOT Name: Olfactory receptor 12D3 (OR12D3)
• Synonyms: Hs6M1-27; Olfactory receptor OR6-27
• Gene Name: OR12D3
• Related Disease:
  Acquired immune deficiency syndrome
  Barrett esophagus
  Breast carcinoma
  Esophageal adenocarcinoma
  Major depressive disorder
  Rheumatoid arthritis
  Sarcoidosis
  Schizophrenia
  Type-1 diabetes
  Type-1/2 diabetes
  Systemic lupus erythematosus
  Asthma
  Lung cancer
• UniProt ID: O12D3_HUMAN
• Pfam ID: PF13853
• Sequence:
  MENVTTMNEFLLLGLTGVQELQPFFFGIFLIIYLINLIGNGSILVMVVLEPQLHSPMYFF
  LGNLSCLDISYSSVTLPKLLVNLVCSRRAISFLGCITQLHFFHFLGSTEAILLAIMAFDR
  FVAICNPLRYTVIMNPQVCILLAAAAWLISFFYALMHSVMTAHLSFCGSQKLNHFFYDVK
  PLLELACSDTLLNQWLLSIVTGSISMGAFFLTLLSCFYVIGFLLFKNRSCRILHKALSTC
  ASHFMVVCLFYGPVGFTYIRPASATSMIQDRIMAIMYSAVTPVLNPLIYTLRNKEVMMAL
  KKIFGRKLFKDWQQHH
• Function: Odorant receptor.
• KEGG Pathway: Olfactory transduction (hsa04740)
• Reactome Pathway: Expression and translocation of olfactory receptors (R-HSA-9752946)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acquired immune deficiency syndrome	DISL5UOX	Strong	Genetic Variation	[1]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[2]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[3]
Esophageal adenocarcinoma	DISODWFP	Strong	Genetic Variation	[2]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[4]
Rheumatoid arthritis	DISTSB4J	Strong	Genetic Variation	[5]
Sarcoidosis	DISE5B8Z	Strong	Genetic Variation	[6]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[7]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[9]
Systemic lupus erythematosus	DISI1SZ7	moderate	Genetic Variation	[10]
Asthma	DISW9QNS	Limited	Genetic Variation	[11]
Lung cancer	DISCM4YA	Limited	Genetic Variation	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Olfactory receptor 12D3 (OR12D3).	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Olfactory receptor 12D3 (OR12D3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Olfactory receptor 12D3 (OR12D3).	[15]

References

• [1] Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02).J Infect Dis. 2009 Feb 1;199(3):419-26. doi: 10.1086/596067.
• [2] Genome-wide association studies in oesophageal adenocarcinoma and Barrett's oesophagus: a large-scale meta-analysis.Lancet Oncol. 2016 Oct;17(10):1363-1373. doi: 10.1016/S1470-2045(16)30240-6. Epub 2016 Aug 12.
• [3] Association analysis identifies 65 new breast cancer risk loci.Nature. 2017 Nov 2;551(7678):92-94. doi: 10.1038/nature24284. Epub 2017 Oct 23.
• [4] Genome-wide association study of depression phenotypes in UK Biobank identifies variants in excitatory synaptic pathways.Nat Commun. 2018 Apr 16;9(1):1470. doi: 10.1038/s41467-018-03819-3.
• [5] REL, encoding a member of the NF-kappaB family of transcription factors, is a newly defined risk locus for rheumatoid arthritis.Nat Genet. 2009 Jul;41(7):820-3. doi: 10.1038/ng.395. Epub 2009 Jun 7.
• [6] High-Density Genetic Mapping Identifies New Susceptibility Variants in Sarcoidosis Phenotypes and Shows Genomic-driven Phenotypic Differences.Am J Respir Crit Care Med. 2016 May 1;193(9):1008-22. doi: 10.1164/rccm.201507-1372OC.
• [7] Genome-Wide Association Study Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [8] A genome-wide association study identifies KIAA0350 as a type 1 diabetes gene.Nature. 2007 Aug 2;448(7153):591-4. doi: 10.1038/nature06010. Epub 2007 Jul 15.
• [9] Mapping eGFR loci to the renal transcriptome and phenome in the VA Million Veteran Program.Nat Commun. 2019 Aug 26;10(1):3842. doi: 10.1038/s41467-019-11704-w.
• [10] GWAS identifies novel SLE susceptibility genes and explains the association of the HLA region.Genes Immun. 2014 Sep;15(6):347-54. doi: 10.1038/gene.2014.23. Epub 2014 May 29.
• [11] Genome-Wide Association Study Identifies Novel Loci Associated With Diisocyanate-Induced Occupational Asthma.Toxicol Sci. 2015 Jul;146(1):192-201. doi: 10.1093/toxsci/kfv084. Epub 2015 Apr 26.
• [12] Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls.Hum Mol Genet. 2012 Nov 15;21(22):4980-95. doi: 10.1093/hmg/dds334. Epub 2012 Aug 16.
• [13] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [14] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [15] 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.