Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP6L08T)

• DOT Name: 5-hydroxytryptamine receptor 3D (HTR3D)
• Synonyms: 5-HT3-D; 5-HT3D; Serotonin receptor 3D
• Gene Name: HTR3D
• Related Disease:
  Angle-closure glaucoma
  Obsessive compulsive disorder
  Primary angle-closure glaucoma
  Schizophrenia
  Stroke
• UniProt ID: 5HT3D_HUMAN
• Pfam ID: PF02931 ; PF02932
• Sequence:
  MQKHSPGPPALALLSQSLLTTGNGDTLIINCPGFGQHRVDPAAFQAVFDRKAIGPVTNYS
  VATHVNISFTLSAIWNCYSRIHTFNCHHARPWHNQFVQWNPDECGGIKKSGMATENLWLS
  DVFIEESVDQTPAGLMASMSIVKATSNTISQCGWSASANWTPSISPSMDRARAWRRMSRS
  FQIHHRTSFRTRREWVLLGIQKRTIKVTVATNQYEQAIFHVAIRRRCRPSPYVVNFLVPS
  GILIAIDALSFYLPLESGNCAPFKMTVLLGYSVFLLMMNDLLPATSTSSHASLVAPLALM
  QTPLPAGVYFALCLSLMVGSLLETIFITHLLHVATTQPLPLPRWLHSLLLHCTGQGRCCP
  TAPQKGNKGPGLTPTHLPGVKEPEVSAGQMPGPGEAELTGGSEWTRAQREHEAQKQHSVE
  LWVQFSHAMDALLFRLYLLFMASSIITVICLWNT
• Function: Forms serotonin (5-hydroxytryptamine/5-HT3)-activated cation-selective channel complexes, which when activated cause fast, depolarizing responses in neurons.
• Tissue Specificity: Expressed in liver, as well as fetal and adult colon and kidney.
• KEGG Pathway:
  Serotonergic sy.pse (hsa04726)
  Taste transduction (hsa04742)
• Reactome Pathway: Neurotransmitter receptors and postsynaptic signal transmission (R-HSA-112314)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angle-closure glaucoma	DISZ95KY	Strong	Genetic Variation	[1]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[2]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Genetic Variation	[1]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]
Stroke	DISX6UHX	Limited	Biomarker	[4]

2 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 decreases the methylation of 5-hydroxytryptamine receptor 3D (HTR3D).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of 5-hydroxytryptamine receptor 3D (HTR3D).	[6]

References

• [1] Genetic Association of the PARL-ABCC5-HTR3D-HTR3C Locus With Primary Angle-Closure Glaucoma in Chinese.Invest Ophthalmol Vis Sci. 2017 Aug 1;58(10):4384?389. doi: 10.1167/iovs.17-22304.
• [2] 5-HT3 receptor influences the washing phenotype and visual organization in obsessive-compulsive disorder supporting 5-HT3 receptor antagonists as novel treatment option.Eur Neuropsychopharmacol. 2014 Jan;24(1):86-94. doi: 10.1016/j.euroneuro.2013.07.003. Epub 2013 Aug 6.
• [3] A coding variant of the novel serotonin receptor subunit 5-HT3E influences sustained attention in schizophrenia patients.Eur Neuropsychopharmacol. 2010 Jun;20(6):414-20. doi: 10.1016/j.euroneuro.2010.02.012. Epub 2010 Mar 30.
• [4] Novel susceptibility genes were found in a targeted sequencing of stroke patients with or without depression in the Chinese Han population.J Affect Disord. 2019 Aug 1;255:1-9. doi: 10.1016/j.jad.2019.05.023. Epub 2019 May 13.
• [5] 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.
• [6] 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.