Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMY8G20)

• DOT Name: Bestrophin-3 (BEST3)
• Synonyms: Vitelliform macular dystrophy 2-like protein 3
• Gene Name: BEST3
• Related Disease:
  Atrial fibrillation
  Barrett esophagus
  Gastroesophageal reflux disease
  Non-insulin dependent diabetes
  Autosomal dominant prognathism
  Familial atrial fibrillation
• UniProt ID: BEST3_HUMAN
• Pfam ID: PF01062
• Sequence:
  MTVTYSSKVANATFFGFHRLLLKWRGSIYKLLYREFIVFAVLYTAISLVYRLLLTGVQKR
  YFEKLSIYCDRYAEQIPVTFVLGFYVTLVVNRWWNQFVNLPWPDRLMFLISSSVHGSDEH
  GRLLRRTLMRYVNLTSLLIFRSVSTAVYKRFPTMDHVVEAGFMTTDERKLFNHLKSPHLK
  YWVPFIWFGNLATKARNEGRIRDSVDLQSLMTEMNRYRSWCSLLFGYDWVGIPLVYTQVV
  TLAVYTFFFACLIGRQFLDPTKGYAGHDLDLYIPIFTLLQFFFYAGWLKVAEQLINPFGE
  DDDDFETNWCIDRNLQVSLLAVDEMHMSLPKMKKDIYWDDSAARPPYTLAAADYCIPSFL
  GSTVQMGLSGSDFPDEEWLWDYEKHGHRHSMIRRVKRFLSAHEHPSSPRRRSYRRQTSDS
  SMFLPRDDLSPARDLLDVPSRNPPRASPTWKKSCFPEGSPTLHFSMGELSTIRETSQTST
  LQSLTPQSSVRTSPIKMPLVPEVLITAAEAPVPTSGGYHHDSATSILSSEFTGVQPSKTE
  QQQGPMGSILSPSEKETPPGGPSPQTVSASAEENIFNCEEDPGDTFLKRWSLPGFLGSSH
  TSLGNLSPDPMSSQPALLIDTETSSEISGINIVAGSRVSSDMLYLMENLDTKETDIIELN
  KETEESPK
• Function: Forms calcium-sensitive chloride channels. Permeable to bicarbonate.
• Tissue Specificity: Present in skeletal muscle and weakly in brain, spinal cord, bone marrow and retina.
• Reactome Pathway: Stimuli-sensing channels (R-HSA-2672351)

Molecular Interaction Atlas (MIA) of This DOT

6 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Atrial fibrillation	DIS15W6U	Strong	Biomarker	[1]
Barrett esophagus	DIS416Y7	Strong	Biomarker	[2]
Gastroesophageal reflux disease	DISQ8G5S	Strong	Genetic Variation	[2]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Genetic Variation	[3]
Autosomal dominant prognathism	DIS2G3FF	moderate	Biomarker	[4]
Familial atrial fibrillation	DISL4AGF	moderate	Biomarker	[1]

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 Bestrophin-3 (BEST3).	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Bestrophin-3 (BEST3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Bestrophin-3 (BEST3).	[7]

References

• [1] Multi-ethnic genome-wide association study for atrial fibrillation.Nat Genet. 2018 Jun 11;50(9):1225-1233. doi: 10.1038/s41588-018-0133-9.
• [2] Barrett's oESophagus trial 3 (BEST3): study protocol for a randomised controlled trial comparing the Cytosponge-TFF3 test with usual care to facilitate the diagnosis of oesophageal pre-cancer in primary care patients with chronic acid reflux.BMC Cancer. 2018 Aug 3;18(1):784. doi: 10.1186/s12885-018-4664-3.
• [3] Genetic Variants in HSD17B3, SMAD3, and IPO11 Impact Circulating Lipids in Response to Fenofibrate in Individuals With Type 2 Diabetes.Clin Pharmacol Ther. 2018 Apr;103(4):712-721. doi: 10.1002/cpt.798. Epub 2017 Nov 3.
• [4] Whole-exome sequencing in a Japanese pedigree implicates a rare non-synonymous single-nucleotide variant in BEST3 as a candidate for mandibular prognathism.Bone. 2019 May;122:193-198. doi: 10.1016/j.bone.2019.03.004. Epub 2019 Mar 5.
• [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] Loss of TRIM33 causes resistance to BET bromodomain inhibitors through MYC- and TGF-beta-dependent mechanisms. Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4558-66.
• [7] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.