Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWHE1ZC)

DOT Name Bestrophin-1 (BEST1)
Synonyms TU15B; Vitelliform macular dystrophy protein 2
Gene Name BEST1
Related Disease
Autosomal recessive bestrophinopathy ( )
High blood pressure ( )
Inherited retinal dystrophy ( )
Neoplasm ( )
Type-1 diabetes ( )
Vitelliform macular dystrophy 2 ( )
Advanced cancer ( )
Ankylosing spondylitis ( )
Anorexia nervosa cachexia ( )
Autosomal dominant vitreoretinochoroidopathy ( )
Breast cancer ( )
Cardiomyopathy ( )
Cardiovascular disease ( )
Chronic obstructive pulmonary disease ( )
Coeliac disease ( )
Crohn disease ( )
Diabetic kidney disease ( )
Dilated cardiomyopathy 3B ( )
Disorder of orbital region ( )
Duchenne muscular dystrophy ( )
Limb-girdle muscular dystrophy ( )
Microphthalmia ( )
Muscular dystrophy ( )
Myopathy ( )
Neuromuscular disease ( )
Non-insulin dependent diabetes ( )
Osteoarthritis ( )
Pancreatic cancer ( )
Peripheral arterial disease ( )
Prader-Willi syndrome ( )
Primary hyperparathyroidism ( )
Prostate cancer ( )
Prostate carcinoma ( )
Retinitis pigmentosa 50 ( )
Retinopathy ( )
Rheumatoid arthritis ( )
Schizophrenia ( )
Vitamin D deficiency ( )
Angle-closure glaucoma ( )
Cystic fibrosis ( )
Adult-onset foveomacular vitelliform dystrophy ( )
MRCS syndrome ( )
Nanophthalmia ( )
Retinitis pigmentosa ( )
Asthma ( )
Becker muscular dystrophy ( )
Bone osteosarcoma ( )
Breast carcinoma ( )
Epithelial ovarian cancer ( )
Macular degeneration ( )
Myocardial infarction ( )
Obesity ( )
Osteosarcoma ( )
Severe early-childhood-onset retinal dystrophy ( )
UniProt ID
BEST1_HUMAN
3D Structure
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2D Sequence (FASTA)
Download
3D Structure (PDB)
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PDB ID
8D1I; 8D1J; 8D1K; 8D1L; 8D1M; 8D1O
Pfam ID
PF01062
Sequence
MTITYTSQVANARLGSFSRLLLCWRGSIYKLLYGEFLIFLLCYYIIRFIYRLALTEEQQL
MFEKLTLYCDSYIQLIPISFVLGFYVTLVVTRWWNQYENLPWPDRLMSLVSGFVEGKDEQ
GRLLRRTLIRYANLGNVLILRSVSTAVYKRFPSAQHLVQAGFMTPAEHKQLEKLSLPHNM
FWVPWVWFANLSMKAWLGGRIRDPILLQSLLNEMNTLRTQCGHLYAYDWISIPLVYTQVV
TVAVYSFFLTCLVGRQFLNPAKAYPGHELDLVVPVFTFLQFFFYVGWLKVAEQLINPFGE
DDDDFETNWIVDRNLQVSLLAVDEMHQDLPRMEPDMYWNKPEPQPPYTAASAQFRRASFM
GSTFNISLNKEEMEFQPNQEDEEDAHAGIIGRFLGLQSHDHHPPRANSRTKLLWPKRESL
LHEGLPKNHKAAKQNVRGQEDNKAWKLKAVDAFKSAPLYQRPGYYSAPQTPLSPTPMFFP
LEPSAPSKLHSVTGIDTKDKSLKTVSSGAKKSFELLSESDGALMEHPEVSQVRRKTVEFN
LTDMPEIPENHLKEPLEQSPTNIHTTLKDHMDPYWALENRDEAHS
Function Forms calcium-sensitive chloride channels. Highly permeable to bicarbonate.
Tissue Specificity Predominantly expressed in the basolateral membrane of the retinal pigment epithelium.
Reactome Pathway
Stimuli-sensing channels (R-HSA-2672351 )

Molecular Interaction Atlas (MIA) of This DOT

54 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Autosomal recessive bestrophinopathy DISU5FU5 Definitive Autosomal recessive [1]
High blood pressure DISY2OHH Definitive Biomarker [2]
Inherited retinal dystrophy DISGGL77 Definitive Autosomal dominant [3]
Neoplasm DISZKGEW Definitive Biomarker [4]
Type-1 diabetes DIS7HLUB Definitive Biomarker [5]
Vitelliform macular dystrophy 2 DISNQ872 Definitive Autosomal dominant [1]
Advanced cancer DISAT1Z9 Strong Genetic Variation [6]
Ankylosing spondylitis DISRC6IR Strong Biomarker [7]
Anorexia nervosa cachexia DISFO5RQ Strong Biomarker [8]
Autosomal dominant vitreoretinochoroidopathy DISXZJ1T Strong Autosomal dominant [9]
Breast cancer DIS7DPX1 Strong Biomarker [10]
Cardiomyopathy DISUPZRG Strong Biomarker [11]
Cardiovascular disease DIS2IQDX Strong Biomarker [12]
Chronic obstructive pulmonary disease DISQCIRF Strong Genetic Variation [13]
Coeliac disease DISIY60C Strong Biomarker [14]
Crohn disease DIS2C5Q8 Strong Biomarker [15]
Diabetic kidney disease DISJMWEY Strong Biomarker [16]
Dilated cardiomyopathy 3B DIS7YC1S Strong Biomarker [17]
Disorder of orbital region DISH0ECJ Strong Genetic Variation [18]
Duchenne muscular dystrophy DISRQ3NV Strong Biomarker [19]
Limb-girdle muscular dystrophy DISI9Y1Z Strong Genetic Variation [20]
Microphthalmia DISGEBES Strong GermlineCausalMutation [21]
Muscular dystrophy DISJD6P7 Strong Genetic Variation [22]
Myopathy DISOWG27 Strong Genetic Variation [23]
Neuromuscular disease DISQTIJZ Strong Genetic Variation [22]
Non-insulin dependent diabetes DISK1O5Z Strong Altered Expression [24]
Osteoarthritis DIS05URM Strong Genetic Variation [25]
Pancreatic cancer DISJC981 Strong Biomarker [26]
Peripheral arterial disease DIS78WFB Strong Altered Expression [27]
Prader-Willi syndrome DISYWMLU Strong Biomarker [28]
Primary hyperparathyroidism DISB4U1Q Strong Biomarker [29]
Prostate cancer DISF190Y Strong Biomarker [30]
Prostate carcinoma DISMJPLE Strong Biomarker [30]
Retinitis pigmentosa 50 DISSNFLI Strong Autosomal dominant [31]
Retinopathy DISB4B0F Strong Genetic Variation [32]
Rheumatoid arthritis DISTSB4J Strong Biomarker [33]
Schizophrenia DISSRV2N Strong Biomarker [34]
Vitamin D deficiency DISAWKYI Strong Genetic Variation [13]
Angle-closure glaucoma DISZ95KY moderate Genetic Variation [35]
Cystic fibrosis DIS2OK1Q moderate Biomarker [36]
Adult-onset foveomacular vitelliform dystrophy DISPYJN2 Supportive Autosomal dominant [37]
MRCS syndrome DIS1F1U3 Supportive Autosomal dominant [38]
Nanophthalmia DISIULDO Supportive Autosomal dominant [21]
Retinitis pigmentosa DISCGPY8 Supportive Autosomal dominant [39]
Asthma DISW9QNS Limited Altered Expression [40]
Becker muscular dystrophy DIS5IYHL Limited Genetic Variation [41]
Bone osteosarcoma DIST1004 Limited Biomarker [25]
Breast carcinoma DIS2UE88 Limited Biomarker [10]
Epithelial ovarian cancer DIS56MH2 Limited Posttranslational Modification [42]
Macular degeneration DISLKKHD Limited Genetic Variation [43]
Myocardial infarction DIS655KI Limited Biomarker [44]
Obesity DIS47Y1K Limited Biomarker [8]
Osteosarcoma DISLQ7E2 Limited Biomarker [25]
Severe early-childhood-onset retinal dystrophy DISFDRFO Limited CausalMutation [45]
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⏷ Show the Full List of 54 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
6 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Bestrophin-1 (BEST1). [46]
Cisplatin DMRHGI9 Approved Cisplatin affects the expression of Bestrophin-1 (BEST1). [47]
Decitabine DMQL8XJ Approved Decitabine affects the expression of Bestrophin-1 (BEST1). [47]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 increases the expression of Bestrophin-1 (BEST1). [49]
THAPSIGARGIN DMDMQIE Preclinical THAPSIGARGIN increases the expression of Bestrophin-1 (BEST1). [50]
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the expression of Bestrophin-1 (BEST1). [51]
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⏷ Show the Full List of 6 Drug(s)
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 increases the methylation of Bestrophin-1 (BEST1). [48]
Coumarin DM0N8ZM Investigative Coumarin decreases the phosphorylation of Bestrophin-1 (BEST1). [52]
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References

1 Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
2 Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers (ACEI/ARB) are Associated with Improved Limb Salvage after Infrapopliteal Interventions for Critical Limb Ischemia.Ann Vasc Surg. 2020 Feb;63:275-286. doi: 10.1016/j.avsg.2019.08.093. Epub 2019 Oct 15.
3 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
4 Loss of angiotensin-converting enzyme 2 promotes growth of gallbladder cancer.Tumour Biol. 2015 Jul;36(7):5171-7. doi: 10.1007/s13277-015-3171-2. Epub 2015 Feb 9.
5 Poor Glycemic Control Is Associated With Impaired Bone Accrual in the Year Following a Diagnosis of Type 1 Diabetes.J Clin Endocrinol Metab. 2019 Oct 1;104(10):4511-4520. doi: 10.1210/jc.2019-00035.
6 Low bone mineral density may be associated with long-term risk of cancer in the middle-aged population: A retrospective observational study from a single center.J Formos Med Assoc. 2018 Apr;117(4):339-345. doi: 10.1016/j.jfma.2017.04.021. Epub 2017 May 16.
7 Long-Term Treatment With TNF-Alpha Inhibitors Improves Bone Mineral Density But Not Vertebral Fracture Progression in Ankylosing Spondylitis.J Bone Miner Res. 2019 Jun;34(6):1041-1048. doi: 10.1002/jbmr.3684. Epub 2019 Mar 25.
8 Suboptimal bone microarchitecure in adolescent girls with obesity compared to normal-weight controls and girls with anorexia nervosa.Bone. 2019 May;122:246-253. doi: 10.1016/j.bone.2019.03.007. Epub 2019 Mar 7.
9 PanelApp crowdsources expert knowledge to establish consensus diagnostic gene panels. Nat Genet. 2019 Nov;51(11):1560-1565. doi: 10.1038/s41588-019-0528-2.
10 Long-term effect of aromatase inhibitors on bone microarchitecture and macroarchitecture in non-osteoporotic postmenopausal women with breast cancer.Osteoporos Int. 2017 Apr;28(4):1413-1422. doi: 10.1007/s00198-016-3899-6. Epub 2017 Jan 12.
11 Interventions for preventing and treating cardiac complications in Duchenne and Becker muscular dystrophy and X-linked dilated cardiomyopathy.Cochrane Database Syst Rev. 2018 Oct 16;10(10):CD009068. doi: 10.1002/14651858.CD009068.pub3.
12 Links between Atherosclerosis and Osteoporosis in Middle Aged and Elderly Men.J Nutr Health Aging. 2018;22(6):639-644. doi: 10.1007/s12603-018-1039-z.
13 Increased rate of osteoporosis, low lean mass, and fragility fractures in COPD patients: association with disease severity.Osteoporos Int. 2018 Jun;29(6):1457-1468. doi: 10.1007/s00198-018-4483-z. Epub 2018 Mar 21.
14 Coeliac disease.Paediatr Int Child Health. 2019 Feb;39(1):23-31. doi: 10.1080/20469047.2018.1504431. Epub 2018 Aug 13.
15 Effects of Recombinant Human Growth Hormone in Children with Crohn's Disease on the Muscle-Bone Unit: A Preliminary Study.Horm Res Paediatr. 2018;90(2):128-131. doi: 10.1159/000492398. Epub 2018 Aug 27.
16 Clinical Efficacy and Safety of Jinshuibao Combined With ACEI/ARB in the Treatment of Diabetic Kidney Disease: A Meta-Analysis of Randomized Controlled Trials.J Ren Nutr. 2020 Mar;30(2):92-100. doi: 10.1053/j.jrn.2019.03.083. Epub 2019 Jun 11.
17 Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human.Neuromuscul Disord. 2007 Dec;17(11-12):913-8. doi: 10.1016/j.nmd.2007.07.005. Epub 2007 Sep 7.
18 Functional roles of bestrophins in ocular epithelia.Prog Retin Eye Res. 2009 May;28(3):206-26. doi: 10.1016/j.preteyeres.2009.04.004. Epub 2009 May 4.
19 Comprehensive genetic characteristics of dystrophinopathies in China.Orphanet J Rare Dis. 2018 Jul 4;13(1):109. doi: 10.1186/s13023-018-0853-z.
20 Value of muscle enzyme measurement in evaluating different neuromuscular diseases.Clin Chim Acta. 2012 Feb 18;413(3-4):520-4. doi: 10.1016/j.cca.2011.11.016. Epub 2011 Nov 25.
21 The spectrum of ocular phenotypes caused by mutations in the BEST1 gene. Prog Retin Eye Res. 2009 May;28(3):187-205. doi: 10.1016/j.preteyeres.2009.04.002. Epub 2009 Apr 16.
22 Mutation spectrum analysis of Duchenne/Becker muscular dystrophy in 68 families in Kuwait: The era of personalized medicine.PLoS One. 2018 May 30;13(5):e0197205. doi: 10.1371/journal.pone.0197205. eCollection 2018.
23 Genetic analysis of the dystrophin gene in children with Duchenne and Becker muscular dystrophies.Muscle Nerve. 2017 Jul;56(1):117-121. doi: 10.1002/mus.25435. Epub 2017 Feb 3.
24 Lipid Levels Related to Osteoporosis in Patients with Type 2 Diabetes.Exp Clin Endocrinol Diabetes. 2019 Jul;127(7):468-472. doi: 10.1055/a-0735-9361. Epub 2018 Sep 20.
25 The role of GPCRs in bone diseases and dysfunctions.Bone Res. 2019 Jul 8;7:19. doi: 10.1038/s41413-019-0059-6. eCollection 2019.
26 Effect of differences in cancer cells and tumor growth sites on recruiting bone marrow-derived endothelial cells and myofibroblasts in cancer-induced stroma.Int J Cancer. 2005 Jul 20;115(6):885-92. doi: 10.1002/ijc.20969.
27 Lower Extremity Peripheral Arterial Disease Is an Independent Predictor of Coronary Heart Disease and Stroke Risks in Patients with Type 2 Diabetes Mellitus in China.Int J Endocrinol. 2017;2017:9620513. doi: 10.1155/2017/9620513. Epub 2017 May 8.
28 Magel2 Modulates Bone Remodeling and Mass in Prader-Willi Syndrome by Affecting Oleoyl Serine Levels and Activity.J Bone Miner Res. 2019 Jan;34(1):93-105. doi: 10.1002/jbmr.3591. Epub 2018 Oct 22.
29 Clinical Impact of p27(Kip1) and CaSR Expression on Primary Hyperparathyroidism.Endocr Pathol. 2018 Sep;29(3):250-258. doi: 10.1007/s12022-018-9524-9.
30 Bone mineral density, structure, distribution and strength in men with prostate cancer treated with androgen deprivation therapy.Bone. 2019 Oct;127:367-375. doi: 10.1016/j.bone.2019.06.005. Epub 2019 Jun 9.
31 Missense mutations in a retinal pigment epithelium protein, bestrophin-1, cause retinitis pigmentosa. Am J Hum Genet. 2009 Nov;85(5):581-92. doi: 10.1016/j.ajhg.2009.09.015. Epub 2009 Oct 22.
32 Molecular mechanisms of gating in the calcium-activated chloride channel bestrophin.Elife. 2019 Jan 10;8:e43231. doi: 10.7554/eLife.43231.
33 Zoledronic acid ameliorates the effects of secondary osteoporosis in rheumatoid arthritis patients.J Orthop Surg Res. 2019 Dec 10;14(1):421. doi: 10.1186/s13018-019-1492-3.
34 Preliminary assessment of intrahemispheric QEEG measures in bipolar mood disorders.Can J Psychiatry. 2002 May;47(4):368-74. doi: 10.1177/070674370204700408.
35 Flat Anterior Chamber after Trabeculectomy in Secondary Angle-Closure Glaucoma with BEST1 Gene Mutation: Case Series.PLoS One. 2017 Jan 5;12(1):e0169395. doi: 10.1371/journal.pone.0169395. eCollection 2017.
36 ER-localized bestrophin 1 activates Ca2+-dependent ion channels TMEM16A and SK4 possibly by acting as a counterion channel.Pflugers Arch. 2010 Feb;459(3):485-97. doi: 10.1007/s00424-009-0745-0. Epub 2009 Oct 13.
37 Mutations in the VMD2 gene are associated with juvenile-onset vitelliform macular dystrophy (Best disease) and adult vitelliform macular dystrophy but not age-related macular degeneration. Eur J Hum Genet. 2000 Apr;8(4):286-92. doi: 10.1038/sj.ejhg.5200447.
38 Mutations of VMD2 splicing regulators cause nanophthalmos and autosomal dominant vitreoretinochoroidopathy (ADVIRC). Invest Ophthalmol Vis Sci. 2004 Oct;45(10):3683-9. doi: 10.1167/iovs.04-0550.
39 Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
40 Long-term effects of inhaled corticosteroids on bone mineral density in older women with asthma or COPD: a registry-based cohort study.Arch Osteoporos. 2018 Oct 29;13(1):116. doi: 10.1007/s11657-018-0537-2.
41 How the central domain of dystrophin acts to bridge F-actin to sarcolemmal lipids.J Struct Biol. 2020 Jan 1;209(1):107411. doi: 10.1016/j.jsb.2019.107411. Epub 2019 Nov 2.
42 Role of 12-lipoxygenase in regulation of ovarian cancer cell proliferation and survival.Cancer Chemother Pharmacol. 2011 Nov;68(5):1273-83. doi: 10.1007/s00280-011-1595-y. Epub 2011 Mar 29.
43 Contribution of Ion Channels in Calcium Signaling Regulating Phagocytosis: MaxiK, Cav1.3 and Bestrophin-1.Adv Exp Med Biol. 2016;854:739-44. doi: 10.1007/978-3-319-17121-0_98.
44 Impact of metabolic syndrome on mean platelet volume and its relationship with coronary artery disease.Platelets. 2019;30(5):615-623. doi: 10.1080/09537104.2018.1499885. Epub 2018 Jul 26.
45 Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.
46 Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
47 Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
48 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.
49 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.
50 Endoplasmic reticulum stress impairs insulin signaling through mitochondrial damage in SH-SY5Y cells. Neurosignals. 2012;20(4):265-80.
51 Bisphenolic compounds alter gene expression in MCF-7 cells through interaction with estrogen receptor . Toxicol Appl Pharmacol. 2020 Jul 15;399:115030. doi: 10.1016/j.taap.2020.115030. Epub 2020 May 6.
52 Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.