Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRBIPR4)

DOT Name B-cell CLL/lymphoma 9 protein (BCL9)
Synonyms B-cell lymphoma 9 protein; Bcl-9; Protein legless homolog
Gene Name BCL9
Related Disease
Juvenile myoclonic epilepsy ( )
LennoxGastaut syndrome ( )
Trichorhinophalangeal syndrome type II ( )
Advanced cancer ( )
B-cell neoplasm ( )
Bipolar disorder ( )
Burkitt lymphoma ( )
Cholangiocarcinoma ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Colorectal carcinoma ( )
Congenital contractural arachnodactyly ( )
Cornelia de Lange syndrome 4 ( )
Dilated cardiomyopathy 1A ( )
Ductal breast carcinoma in situ ( )
Epilepsy ( )
Epithelial ovarian cancer ( )
Hepatitis C virus infection ( )
Hepatocellular carcinoma ( )
Intestinal neoplasm ( )
Knee osteoarthritis ( )
Lung cancer ( )
Lung carcinoma ( )
Major depressive disorder ( )
Mental disorder ( )
Neoplasm ( )
Non-insulin dependent diabetes ( )
Osteoarthritis ( )
Ovarian cancer ( )
Ovarian neoplasm ( )
Plasma cell myeloma ( )
Psychotic disorder ( )
Small lymphocytic lymphoma ( )
Familial adenomatous polyposis ( )
Gastric cancer ( )
Lymphoplasmacytic lymphoma ( )
Schizophrenia ( )
Stomach cancer ( )
Waldenstrom macroglobulinemia ( )
Acute lymphocytic leukaemia ( )
Adrenocortical carcinoma ( )
Aplasia cutis congenita ( )
Bone osteosarcoma ( )
Childhood acute lymphoblastic leukemia ( )
Congenital heart disease ( )
Corpus callosum, agenesis of ( )
Osteosarcoma ( )
UniProt ID
BCL9_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2GL7; 2VP7; 2VPB; 2VPD; 2VPE; 2VPG; 3SL9
Pfam ID
PF11502
Sequence
MHSSNPKVRSSPSGNTQSSPKSKQEVMVRPPTVMSPSGNPQLDSKFSNQGKQGGSASQSQ
PSPCDSKSGGHTPKALPGPGGSMGLKNGAGNGAKGKGKRERSISADSFDQRDPGTPNDDS
DIKECNSADHIKSQDSQHTPHSMTPSNATAPRSSTPSHGQTTATEPTPAQKTPAKVVYVF
STEMANKAAEAVLKGQVETIVSFHIQNISNNKTERSTAPLNTQISALRNDPKPLPQQPPA
PANQDQNSSQNTRLQPTPPIPAPAPKPAAPPRPLDRESPGVENKLIPSVGSPASSTPLPP
DGTGPNSTPNNRAVTPVSQGSNSSSADPKAPPPPPVSSGEPPTLGENPDGLSQEQLEHRE
RSLQTLRDIQRMLFPDEKEFTGAQSGGPQQNPGVLDGPQKKPEGPIQAMMAQSQSLGKGP
GPRTDVGAPFGPQGHRDVPFSPDEMVPPSMNSQSGTIGPDHLDHMTPEQIAWLKLQQEFY
EEKRRKQEQVVVQQCSLQDMMVHQHGPRGVVRGPPPPYQMTPSEGWAPGGTEPFSDGINM
PHSLPPRGMAPHPNMPGSQMRLPGFAGMINSEMEGPNVPNPASRPGLSGVSWPDDVPKIP
DGRNFPPGQGIFSGPGRGERFPNPQGLSEEMFQQQLAEKQLGLPPGMAMEGIRPSMEMNR
MIPGSQRHMEPGNNPIFPRIPVEGPLSPSRGDFPKGIPPQMGPGRELEFGMVPSGMKGDV
NLNVNMGSNSQMIPQKMREAGAGPEEMLKLRPGGSDMLPAQQKMVPLPFGEHPQQEYGMG
PRPFLPMSQGPGSNSGLRNLREPIGPDQRTNSRLSHMPPLPLNPSSNPTSLNTAPPVQRG
LGRKPLDISVAGSQVHSPGINPLKSPTMHQVQSPMLGSPSGNLKSPQTPSQLAGMLAGPA
AAASIKSPPVLGSAAASPVHLKSPSLPAPSPGWTSSPKPPLQSPGIPPNHKAPLTMASPA
MLGNVESGGPPPPTASQPASVNIPGSLPSSTPYTMPPEPTLSQNPLSIMMSRMSKFAMPS
STPLYHDAIKTVASSDDDSPPARSPNLPSMNNMPGMGINTQNPRISGPNPVVPMPTLSPM
GMTQPLSHSNQMPSPNAVGPNIPPHGVPMGPGLMSHNPIMGHGSQEPPMVPQGRMGFPQG
FPPVQSPPQQVPFPHNGPSGGQGSFPGGMGFPGEGPLGRPSNLPQSSADAALCKPGGPGG
PDSFTVLGNSMPSVFTDPDLQEVIRPGATGIPEFDLSRIIPSEKPSQTLQYFPRGEVPGR
KQPQGPGPGFSHMQGMMGEQAPRMGLALPGMGGPGPVGTPDIPLGTAPSMPGHNPMRPPA
FLQQGMMGPHHRMMSPAQSTMPGQPTLMSNPAAAVGMIPGKDRGPAGLYTHPGPVGSPGM
MMSMQGMMGPQQNIMIPPQMRPRGMAADVGMGGFSQGPGNPGNMMF
Function Involved in signal transduction through the Wnt pathway. Promotes beta-catenin's transcriptional activity.
Tissue Specificity Detected at low levels in thymus, prostate, testis, ovary and small intestine, and at lower levels in spleen, colon and blood.
Reactome Pathway
Deactivation of the beta-catenin transactivating complex (R-HSA-3769402 )
Formation of the beta-catenin (R-HSA-201722 )

Molecular Interaction Atlas (MIA) of This DOT

48 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Juvenile myoclonic epilepsy DISYXV1N Definitive Genetic Variation [1]
LennoxGastaut syndrome DISOTGO5 Definitive Genetic Variation [1]
Trichorhinophalangeal syndrome type II DISW4YZ1 Definitive Genetic Variation [1]
Advanced cancer DISAT1Z9 Strong Genetic Variation [2]
B-cell neoplasm DISVY326 Strong Genetic Variation [3]
Bipolar disorder DISAM7J2 Strong Biomarker [4]
Burkitt lymphoma DIS9D5XU Strong Genetic Variation [5]
Cholangiocarcinoma DIS71F6X Strong Biomarker [6]
Colon cancer DISVC52G Strong Biomarker [7]
Colon carcinoma DISJYKUO Strong Biomarker [8]
Colonic neoplasm DISSZ04P Strong Altered Expression [7]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [9]
Congenital contractural arachnodactyly DISOM1K7 Strong Biomarker [6]
Cornelia de Lange syndrome 4 DISXRJCA Strong Genetic Variation [10]
Dilated cardiomyopathy 1A DIS0RK9Z Strong Biomarker [8]
Ductal breast carcinoma in situ DISLCJY7 Strong Biomarker [8]
Epilepsy DISBB28L Strong Biomarker [11]
Epithelial ovarian cancer DIS56MH2 Strong Altered Expression [3]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [12]
Hepatocellular carcinoma DIS0J828 Strong Altered Expression [13]
Intestinal neoplasm DISK0GUH Strong Biomarker [14]
Knee osteoarthritis DISLSNBJ Strong Biomarker [15]
Lung cancer DISCM4YA Strong Biomarker [16]
Lung carcinoma DISTR26C Strong Biomarker [16]
Major depressive disorder DIS4CL3X Strong Biomarker [4]
Mental disorder DIS3J5R8 Strong Biomarker [4]
Neoplasm DISZKGEW Strong Genetic Variation [9]
Non-insulin dependent diabetes DISK1O5Z Strong Genetic Variation [17]
Osteoarthritis DIS05URM Strong Genetic Variation [18]
Ovarian cancer DISZJHAP Strong Altered Expression [3]
Ovarian neoplasm DISEAFTY Strong Altered Expression [3]
Plasma cell myeloma DIS0DFZ0 Strong Biomarker [8]
Psychotic disorder DIS4UQOT Strong Biomarker [4]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [19]
Familial adenomatous polyposis DISW53RE moderate Genetic Variation [20]
Gastric cancer DISXGOUK moderate Altered Expression [21]
Lymphoplasmacytic lymphoma DISMSQ11 moderate Altered Expression [22]
Schizophrenia DISSRV2N moderate Genetic Variation [23]
Stomach cancer DISKIJSX moderate Altered Expression [21]
Waldenstrom macroglobulinemia DIS9O23I moderate Altered Expression [22]
Acute lymphocytic leukaemia DISPX75S Limited Altered Expression [19]
Adrenocortical carcinoma DISZF4HX Limited Biomarker [24]
Aplasia cutis congenita DISMDAYM Limited Altered Expression [24]
Bone osteosarcoma DIST1004 Limited Altered Expression [25]
Childhood acute lymphoblastic leukemia DISJ5D6U Limited Altered Expression [19]
Congenital heart disease DISQBA23 Limited Autosomal dominant [26]
Corpus callosum, agenesis of DISO9P40 Limited Altered Expression [24]
Osteosarcoma DISLQ7E2 Limited Altered Expression [25]
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⏷ Show the Full List of 48 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [27]
Marinol DM70IK5 Approved Marinol increases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [28]
Cannabidiol DM0659E Approved Cannabidiol increases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [29]
Irinotecan DMP6SC2 Approved Irinotecan increases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [30]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [31]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [33]
Calphostin C DM9X2D0 Terminated Calphostin C increases the expression of B-cell CLL/lymphoma 9 protein (BCL9). [35]
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⏷ Show the Full List of 7 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 affects the methylation of B-cell CLL/lymphoma 9 protein (BCL9). [32]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 affects the phosphorylation of B-cell CLL/lymphoma 9 protein (BCL9). [34]
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References

1 Association of GABAA Receptor Gene with Epilepsy Syndromes.J Mol Neurosci. 2018 Jun;65(2):141-153. doi: 10.1007/s12031-018-1081-7. Epub 2018 May 21.
2 Loss of BCL9/9l suppresses Wnt driven tumourigenesis in models that recapitulate human cancer.Nat Commun. 2019 Feb 13;10(1):723. doi: 10.1038/s41467-019-08586-3.
3 Mechanism of Low Expression of miR-30a-5p on Epithelial-Mesenchymal Transition and Metastasis in Ovarian Cancer.DNA Cell Biol. 2019 Apr;38(4):341-351. doi: 10.1089/dna.2018.4396. Epub 2019 Mar 6.
4 Common variants in the BCL9 gene conferring risk of schizophrenia.Arch Gen Psychiatry. 2011 Mar;68(3):232-40. doi: 10.1001/archgenpsychiatry.2011.1.
5 Structural genome variations in individuals with childhood cancer and tumour predisposition syndromes.Eur J Cancer. 2013 Jun;49(9):2170-8. doi: 10.1016/j.ejca.2013.02.002. Epub 2013 Mar 6.
6 Long non-coding RNA NNT-AS1 functions as an oncogenic gene through modulating miR-485/BCL9 in cholangiocarcinoma.Cancer Manag Res. 2019 Aug 15;11:7739-7749. doi: 10.2147/CMAR.S207801. eCollection 2019.
7 BCL9-2 promotes early stages of intestinal tumor progression.Gastroenterology. 2011 Oct;141(4):1359-70, 1370.e1-3. doi: 10.1053/j.gastro.2011.06.039. Epub 2011 Jun 23.
8 Expression profiling of in vivo ductal carcinoma in situ progression models identified B cell lymphoma-9 as a molecular driver of breast cancer invasion.Breast Cancer Res. 2015 Sep 17;17:128. doi: 10.1186/s13058-015-0630-z.
9 Bcl9 and Pygo synergise downstream of Apc to effect intestinal neoplasia in FAP mouse models.Nat Commun. 2019 Feb 13;10(1):724. doi: 10.1038/s41467-018-08164-z.
10 Prenatal diagnosis and array comparative genomic hybridization characterization of interstitial deletions of 8q23.3-q24.11 and 8q24.13 associated with Langer-Giedion syndrome, Cornelia de Lange syndrome and haploinsufficiency of TRPS1, RAD21 and EXT1.Taiwan J Obstet Gynecol. 2015 Oct;54(5):592-6. doi: 10.1016/j.tjog.2015.08.013.
11 Pathogenesis of Lennox-Gastaut syndrome: considerations and hypotheses.Epileptic Disord. 2001 Dec;3(4):183-96.
12 Up-regulation of proproliferative genes and the ligand/receptor pair placental growth factor and vascular endothelial growth factor receptor 1 in hepatitis C cirrhosis.Liver Int. 2007 Sep;27(7):960-8. doi: 10.1111/j.1478-3231.2007.01542.x.
13 MicroRNA-3194-3p inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by decreasing Wnt/-catenin signaling through targeting BCL9.Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3885-3895. doi: 10.1080/21691401.2019.1670190.
14 LEF1 and B9L shield -catenin from inactivation by Axin, desensitizing colorectal cancer cells to tankyrase inhibitors.Cancer Res. 2014 Mar 1;74(5):1495-505. doi: 10.1158/0008-5472.CAN-13-2682. Epub 2014 Jan 13.
15 Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study.Osteoporos Int. 2010 Jan;21(1):109-18. doi: 10.1007/s00198-009-0931-0. Epub 2009 Apr 17.
16 BCL9 promotes epithelial mesenchymal transition and invasion in cisplatin resistant NSCLC cells via -catenin pathway.Life Sci. 2018 Sep 1;208:284-294. doi: 10.1016/j.lfs.2018.07.023. Epub 2018 Jul 23.
17 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.
18 Wnt-related genes and large-joint osteoarthritis: association study and replication.Rheumatol Int. 2013 Nov;33(11):2875-80. doi: 10.1007/s00296-013-2821-1. Epub 2013 Jul 18.
19 MEF2D-BCL9 Fusion Gene Is Associated With High-Risk Acute B-Cell Precursor Lymphoblastic Leukemia in Adolescents.J Clin Oncol. 2016 Oct 1;34(28):3451-9. doi: 10.1200/JCO.2016.66.5547. Epub 2016 Aug 9.
20 Mixed adenoneuroendocrine carcinoma of the colon: molecular pathogenesis and treatment.Anticancer Res. 2014 Oct;34(10):5517-21.
21 Expression of miR-30c and BCL-9 in gastric carcinoma tissues and their function in the development of gastric cancer.Oncol Lett. 2018 Aug;16(2):2416-2426. doi: 10.3892/ol.2018.8934. Epub 2018 Jun 8.
22 The Cyclophilin A-CD147 complex promotes the proliferation and homing of multiple myeloma cells.Nat Med. 2015 Jun;21(6):572-80. doi: 10.1038/nm.3867. Epub 2015 May 25.
23 Association study of BCL9 gene polymorphism rs583583 with schizophrenia and negative symptoms in Japanese population.Sci Rep. 2015 Oct 23;5:15705. doi: 10.1038/srep15705.
24 BCL9 Upregulation in Adrenocortical Carcinoma: A Novel Wnt/-Catenin Activating Event Driving Adrenocortical Malignancy.J Am Coll Surg. 2018 Jun;226(6):988-995. doi: 10.1016/j.jamcollsurg.2018.01.051. Epub 2018 Feb 8.
25 MicroRNA-1301 inhibits migration and invasion of osteosarcoma cells by targeting BCL9.Gene. 2018 Dec 30;679:100-107. doi: 10.1016/j.gene.2018.08.078. Epub 2018 Aug 30.
26 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.
27 Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
28 THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
29 Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
30 In vitro and in vivo irinotecan-induced changes in expression profiles of cell cycle and apoptosis-associated genes in acute myeloid leukemia cells. Mol Cancer Ther. 2005 Jun;4(6):885-900.
31 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
32 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.
33 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.
34 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.
35 Targeting the beta-catenin/TCF transcriptional complex in the treatment of multiple myeloma. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7516-21. doi: 10.1073/pnas.0610299104. Epub 2007 Apr 23.