Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT65ZLIJ)

DOT Name	5-hydroxytryptamine receptor 3C (HTR3C)
Synonyms	5-HT3-C; 5-HT3C; Serotonin receptor 3C
Gene Name	HTR3C
Related Disease	Advanced cancer ( ) Angle-closure glaucoma ( ) Autism ( ) Autism spectrum disorder ( ) Barrett esophagus ( ) Esophageal adenocarcinoma ( ) Obsessive compulsive disorder ( ) Primary angle-closure glaucoma ( ) Breast cancer ( ) Breast carcinoma ( )
UniProt ID	5HT3C_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF02931 ; PF02932
Sequence	MEGGWPARQSALLCLTVSLLLQGRGDAFTINCSGFDQHGVDPAVFQAVFDRKAFRPFTNY SIPTRVNISFTLSAILGVDAQLQLLTSFLWMDLVWDNPFINWNPKECVGINKLTVLAENL WLPDIFIVESMDVDQTPSGLTAYISSEGRIKYDKPMRVTSICNLDIFYFPFDQQNCTFTF SSFLYTVDSMLLGMDKEVWEITDTSRKVIQTQGEWELLGINKATPKMSMGNNLYDQIMFY VAIRRRPSLYIINLLVPSSFLVAIDALSFYLPAESENRAPFKITLLLGYNVFLLMMNDLL PASGTPLISVYFALCLSLMVVSLLETVFITYLLHVATTQPPPMPRWLHSLLLHCTSPGRC CPTAPQKGNKGLGLTLTHLPGPKEPGELAGKKLGPRETEPDGGSGWTKTQLMELWVQFSH AMDTLLFRLYLLFMASSILTVIVLWNT
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 many tissues including adult brain, colon, intestine, lung, muscle and stomach as well as fetal 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

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Angle-closure glaucoma	DISZ95KY	Strong	Genetic Variation	[2]
Autism	DISV4V1Z	Strong	Genetic Variation	[3]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[3]
Barrett esophagus	DIS416Y7	Strong	Genetic Variation	[4]
Esophageal adenocarcinoma	DISODWFP	Strong	Genetic Variation	[4]
Obsessive compulsive disorder	DIS1ZMM2	Strong	Genetic Variation	[5]
Primary angle-closure glaucoma	DISX8UKZ	Strong	Genetic Variation	[2]
Breast cancer	DIS7DPX1	Limited	Biomarker	[6]
Breast carcinoma	DIS2UE88	Limited	Biomarker	[6]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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 decreases the methylation of 5-hydroxytryptamine receptor 3C (HTR3C).	[7]
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1 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of 5-hydroxytryptamine receptor 3C (HTR3C).	[8]
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References

1	Investigation of HTR3C mutations for association with 5HT(3) receptor antagonist anti-emetic efficacy.Pharmacogenomics. 2008 Aug;9(8):1027-33. doi: 10.2217/14622416.9.8.1027.
2	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.
3	Allelic variants in HTR3C show association with autism.Am J Med Genet B Neuropsychiatr Genet. 2009 Jul 5;150B(5):741-6. doi: 10.1002/ajmg.b.30882.
4	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.
5	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.
6	Association between variants of 5-hydroxytryptamine receptor 3C (HTR3C) and chemotherapy-induced symptoms in women receiving adjuvant treatment for breast cancer.Breast Cancer Res Treat. 2014 Feb;144(1):123-31. doi: 10.1007/s10549-014-2832-y. Epub 2014 Jan 30.
7	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.
8	Effects of bisphenol A on the proliferation, migration, and tumor growth of colon cancer cells: In vitro and in vivo evaluation with mechanistic insights related to ERK and 5-HT3. Food Chem Toxicol. 2021 Dec;158:112662. doi: 10.1016/j.fct.2021.112662. Epub 2021 Nov 4.