Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS6IFZY)

DOT Name Bcl-2-like protein 12 (BCL2L12)
Synonyms Bcl2-L-12; Bcl-2-related proline-rich protein
Gene Name BCL2L12
Related Disease
Acute myelogenous leukaemia ( )
Rheumatoid arthritis ( )
Bladder cancer ( )
Breast cancer ( )
Breast carcinoma ( )
Breast neoplasm ( )
Cardiac failure ( )
Childhood acute lymphoblastic leukemia ( )
Colon cancer ( )
Colon carcinoma ( )
Colonic neoplasm ( )
Congestive heart failure ( )
Craniosynostosis ( )
Cutaneous melanoma ( )
Cutaneous squamous cell carcinoma ( )
Fanconi anemia complementation group A ( )
Fanconi's anemia ( )
Friedreich ataxia 1 ( )
Gastric cancer ( )
Glioblastoma multiforme ( )
Glioma ( )
Head-neck squamous cell carcinoma ( )
Hepatitis C virus infection ( )
Inflammatory bowel disease ( )
Kidney cancer ( )
Laryngeal disorder ( )
Liver cirrhosis ( )
Lung cancer ( )
Lung carcinoma ( )
Metastatic malignant neoplasm ( )
Nasopharyngeal carcinoma ( )
Renal carcinoma ( )
Small lymphocytic lymphoma ( )
Stomach cancer ( )
Triple negative breast cancer ( )
Ulcerative colitis ( )
Urinary bladder cancer ( )
Urinary bladder neoplasm ( )
Vitiligo ( )
Hepatocellular carcinoma ( )
Laryngeal squamous cell carcinoma ( )
Adult glioblastoma ( )
Advanced cancer ( )
B-cell neoplasm ( )
Epstein barr virus infection ( )
Malignant tumor of nasopharynx ( )
Neoplasm ( )
UniProt ID
B2L12_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGRPAGLFPPLCPFLGFRPEACWERHMQIERAPSVPPFLRWAGYRPGPVRRRGKVELIKF
VRVQWRRPQVEWRRRRWGPGPGASMAGSEELGLREDTLRVLAAFLRRGEAAGSPVPTPPR
SPAQEEPTDFLSRLRRCLPCSLGRGAAPSESPRPCSLPIRPCYGLEPGPATPDFYALVAQ
RLEQLVQEQLKSPPSPELQGPPSTEKEAILRRLVALLEEEAEVINQKLASDPALRSKLVR
LSSDSFARLVELFCSRDDSSRPSRACPGPPPPSPEPLARLALAMELSRRVAGLGGTLAGL
SVEHVHSFTPWIQAHGGWEGILAVSPVDLNLPLD
Tissue Specificity
Expressed mainly in breast, thymus, prostate, fetal liver, colon, placenta, pancreas, small intestine, spinal cord, kidney, and bone marrow and to a lesser extent in many other tissues. Isoform 2 is primarily expressed in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

47 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Acute myelogenous leukaemia DISCSPTN Definitive Altered Expression [1]
Rheumatoid arthritis DISTSB4J Definitive Altered Expression [2]
Bladder cancer DISUHNM0 Strong Altered Expression [3]
Breast cancer DIS7DPX1 Strong Altered Expression [4]
Breast carcinoma DIS2UE88 Strong Altered Expression [4]
Breast neoplasm DISNGJLM Strong Biomarker [5]
Cardiac failure DISDC067 Strong Altered Expression [6]
Childhood acute lymphoblastic leukemia DISJ5D6U Strong Altered Expression [7]
Colon cancer DISVC52G Strong Posttranslational Modification [8]
Colon carcinoma DISJYKUO Strong Posttranslational Modification [8]
Colonic neoplasm DISSZ04P Strong Biomarker [8]
Congestive heart failure DIS32MEA Strong Altered Expression [6]
Craniosynostosis DIS6J405 Strong Biomarker [9]
Cutaneous melanoma DIS3MMH9 Strong Genetic Variation [10]
Cutaneous squamous cell carcinoma DIS3LXUG Strong Genetic Variation [10]
Fanconi anemia complementation group A DIS8PZLI Strong Biomarker [11]
Fanconi's anemia DISGW6Q8 Strong Biomarker [11]
Friedreich ataxia 1 DIS285GE Strong Biomarker [11]
Gastric cancer DISXGOUK Strong Biomarker [12]
Glioblastoma multiforme DISK8246 Strong Biomarker [13]
Glioma DIS5RPEH Strong Biomarker [14]
Head-neck squamous cell carcinoma DISF7P24 Strong Altered Expression [15]
Hepatitis C virus infection DISQ0M8R Strong Biomarker [16]
Inflammatory bowel disease DISGN23E Strong Altered Expression [17]
Kidney cancer DISBIPKM Strong Biomarker [18]
Laryngeal disorder DISDKUQO Strong Biomarker [15]
Liver cirrhosis DIS4G1GX Strong Genetic Variation [16]
Lung cancer DISCM4YA Strong Altered Expression [19]
Lung carcinoma DISTR26C Strong Altered Expression [19]
Metastatic malignant neoplasm DIS86UK6 Strong Altered Expression [20]
Nasopharyngeal carcinoma DISAOTQ0 Strong Biomarker [21]
Renal carcinoma DISER9XT Strong Biomarker [18]
Small lymphocytic lymphoma DIS30POX Strong Altered Expression [22]
Stomach cancer DISKIJSX Strong Biomarker [12]
Triple negative breast cancer DISAMG6N Strong Altered Expression [23]
Ulcerative colitis DIS8K27O Strong Altered Expression [24]
Urinary bladder cancer DISDV4T7 Strong Altered Expression [3]
Urinary bladder neoplasm DIS7HACE Strong Altered Expression [3]
Vitiligo DISR05SL Strong Genetic Variation [25]
Hepatocellular carcinoma DIS0J828 moderate Altered Expression [26]
Laryngeal squamous cell carcinoma DIS9UUVF moderate Biomarker [27]
Adult glioblastoma DISVP4LU Limited Biomarker [23]
Advanced cancer DISAT1Z9 Limited Altered Expression [21]
B-cell neoplasm DISVY326 Limited Altered Expression [28]
Epstein barr virus infection DISOO0WT Limited Genetic Variation [29]
Malignant tumor of nasopharynx DISTGIGF Limited Altered Expression [21]
Neoplasm DISZKGEW Limited Biomarker [27]
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⏷ Show the Full List of 47 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
3 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Bcl-2-like protein 12 (BCL2L12). [30]
Arsenic DMTL2Y1 Approved Arsenic affects the methylation of Bcl-2-like protein 12 (BCL2L12). [33]
PMID28870136-Compound-52 DMFDERP Patented PMID28870136-Compound-52 decreases the phosphorylation of Bcl-2-like protein 12 (BCL2L12). [40]
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14 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Bcl-2-like protein 12 (BCL2L12). [31]
Doxorubicin DMVP5YE Approved Doxorubicin decreases the expression of Bcl-2-like protein 12 (BCL2L12). [32]
Cisplatin DMRHGI9 Approved Cisplatin decreases the expression of Bcl-2-like protein 12 (BCL2L12). [32]
Calcitriol DM8ZVJ7 Approved Calcitriol decreases the expression of Bcl-2-like protein 12 (BCL2L12). [34]
Testosterone DM7HUNW Approved Testosterone decreases the expression of Bcl-2-like protein 12 (BCL2L12). [34]
Methotrexate DM2TEOL Approved Methotrexate decreases the expression of Bcl-2-like protein 12 (BCL2L12). [35]
Menthol DMG2KW7 Approved Menthol decreases the expression of Bcl-2-like protein 12 (BCL2L12). [36]
Topotecan DMP6G8T Approved Topotecan decreases the expression of Bcl-2-like protein 12 (BCL2L12). [37]
Eicosapentaenoic acid/docosa-hexaenoic acid DMMUCG4 Approved Eicosapentaenoic acid/docosa-hexaenoic acid decreases the expression of Bcl-2-like protein 12 (BCL2L12). [38]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Bcl-2-like protein 12 (BCL2L12). [39]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Bcl-2-like protein 12 (BCL2L12). [41]
Trichostatin A DM9C8NX Investigative Trichostatin A affects the expression of Bcl-2-like protein 12 (BCL2L12). [42]
Coumestrol DM40TBU Investigative Coumestrol increases the expression of Bcl-2-like protein 12 (BCL2L12). [43]
3R14S-OCHRATOXIN A DM2KEW6 Investigative 3R14S-OCHRATOXIN A decreases the expression of Bcl-2-like protein 12 (BCL2L12). [44]
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⏷ Show the Full List of 14 Drug(s)

References

1 MiR-182-5p regulates BCL2L12 and BCL2 expression in acute myeloid leukemia as a potential therapeutic target.Biomed Pharmacother. 2018 Jan;97:1189-1194. doi: 10.1016/j.biopha.2017.11.002. Epub 2017 Nov 11.
2 Bcl2 like protein-12 suppresses Foxp3(+) regulatory T cells in patients with rheumatoid arthritis.Am J Transl Res. 2019 May 15;11(5):3048-3055. eCollection 2019.
3 Increased BCL2L12 expression predicts the short-term relapse of patients with TaT1 bladder cancer following transurethral resection of bladder tumors.Urol Oncol. 2014 Jan;32(1):39.e29-36. doi: 10.1016/j.urolonc.2013.04.005. Epub 2013 Jun 18.
4 Breathing New Life into TRAIL for Breast Cancer Therapy: Co-Delivery of pTRAIL and Complementary siRNAs Using Lipopolymers.Hum Gene Ther. 2019 Dec;30(12):1531-1546. doi: 10.1089/hum.2019.096. Epub 2019 Oct 29.
5 Expression of BCL2L12, a new member of apoptosis-related genes, in breast tumors.Thromb Haemost. 2003 Jun;89(6):1081-8.
6 Bcl2-Like Protein 12 Is Required for the Aberrant T Helper-2 Polarization in the Heart by Enhancing Interleukin-4 Expression and Compromising Apoptotic Machinery in CD4+ T Cells.Circulation. 2018 Nov 27;138(22):2559-2568. doi: 10.1161/CIRCULATIONAHA.118.033890.
7 BCL2L12 improves risk stratification and prediction of BFM-chemotherapy response in childhood acute lymphoblastic leukemia.Clin Chem Lab Med. 2018 Nov 27;56(12):2104-2118. doi: 10.1515/cclm-2018-0507.
8 Quantitative expression analysis and prognostic significance of the novel apoptosis-related gene BCL2L12 in colon cancer.Biol Chem. 2008 Dec;389(12):1467-75. doi: 10.1515/BC.2008.173.
9 B cell lymphoma-2-like protein-12 association with T-helper 2 inflammation in chronic rhinosinusitis with allergy.Int Forum Allergy Rhinol. 2018 Nov;8(11):1300-1307. doi: 10.1002/alr.22223. Epub 2018 Oct 3.
10 Identifying recurrent mutations in cancer reveals widespread lineage diversity and mutational specificity.Nat Biotechnol. 2016 Feb;34(2):155-63. doi: 10.1038/nbt.3391. Epub 2015 Nov 30.
11 Bcl2L12 plays a critical role in the development of intestinal allergy.Immunol Lett. 2018 Nov;203:87-94. doi: 10.1016/j.imlet.2018.09.001. Epub 2018 Sep 5.
12 Molecular analysis and prognostic impact of the novel apoptotic gene BCL2L12 in gastric cancer.Biochem Biophys Res Commun. 2010 Jan 1;391(1):214-8. doi: 10.1016/j.bbrc.2009.11.034. Epub 2009 Nov 10.
13 miRNA-182 and the regulation of the glioblastoma phenotype - toward miRNA-based precision therapeutics.Cell Cycle. 2015;14(24):3794-800. doi: 10.1080/15384101.2015.1093711.
14 Bcl2L12 with a BH3-like domain in regulating apoptosis and TMZ-induced autophagy: a prospective combination of ABT-737 and TMZ for treating glioma.Int J Oncol. 2015 Mar;46(3):1304-16. doi: 10.3892/ijo.2015.2838. Epub 2015 Jan 13.
15 Quantitative expression analysis of the apoptosis-related gene, BCL2L12, in head and neck squamous cell carcinoma.J Oral Pathol Med. 2013 Feb;42(2):154-61. doi: 10.1111/j.1600-0714.2012.01190.x. Epub 2012 Jul 2.
16 A polymorphism linked to RRAS, SCAF1, IRF3 and BCL2L12 genes is associated with cirrhosis in hepatitis C virus carriers.Liver Int. 2014 Apr;34(4):558-66. doi: 10.1111/liv.12330. Epub 2013 Oct 16.
17 Tumor necrosis factor suppresses interleukin 10 in peripheral B cells via upregulating Bcl2-like protein 12 in patients with inflammatory bowel disease.Cell Biochem Funct. 2017 Mar;35(2):77-82. doi: 10.1002/cbf.3250. Epub 2017 Jan 24.
18 Gemcitabine impacts differentially on bladder and kidney cancer cells: distinct modulations in the expression patterns of apoptosis-related microRNAs and BCL2 family genes.Tumour Biol. 2015 May;36(5):3197-207. doi: 10.1007/s13277-014-2190-8. Epub 2015 Apr 2.
19 Proteinase-activated receptor-2 enhances Bcl2-like protein-12 expression in lung cancer cells to suppress p53 expression.Arch Med Sci. 2019 Sep;15(5):1147-1153. doi: 10.5114/aoms.2019.86980. Epub 2019 Aug 2.
20 BCL2L12 is a novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma.Mol Med. 2011 Mar-Apr;17(3-4):163-71. doi: 10.2119/molmed.2010.00056. Epub 2010 Dec 8.
21 Histone acetyltransferase 1 up regulates Bcl2L12 expression in nasopharyngeal cancer cells.Arch Biochem Biophys. 2018 May 15;646:72-79. doi: 10.1016/j.abb.2018.03.040. Epub 2018 Apr 3.
22 Expression of Bcl2L12 in chronic lymphocytic leukemia patients: association with clinical and molecular prognostic markers.Med Oncol. 2013 Mar;30(1):405. doi: 10.1007/s12032-012-0405-7. Epub 2013 Jan 5.
23 Differential roles of Bcl2L12 and its short variant in breast cancer lymph node metastasis.Oncol Rep. 2015 Aug;34(2):961-71. doi: 10.3892/or.2015.4071. Epub 2015 Jun 16.
24 Bcl2L12 mediates effects of protease-activated receptor-2 on the pathogenesis of Th2-dominated responses of patients with ulcerative colitis.Arch Biochem Biophys. 2018 Nov 1;657:8-14. doi: 10.1016/j.abb.2018.09.003. Epub 2018 Sep 11.
25 Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
26 Stress Hormone Cortisol Enhances Bcl2 Like-12 Expression to Inhibit p53 in Hepatocellular Carcinoma Cells.Dig Dis Sci. 2017 Dec;62(12):3495-3500. doi: 10.1007/s10620-017-4798-1. Epub 2017 Oct 17.
27 Positive BCL2L12 expression predicts favorable prognosis in patients with laryngeal squamous cell carcinoma.Cancer Biomark. 2019;25(2):141-149. doi: 10.3233/CBM-181772.
28 Long noncoding RNA NEAT1 sponges miR?25a?p to suppress cardiomyocyte apoptosis via BCL2L12.Mol Med Rep. 2019 May;19(5):4468-4474. doi: 10.3892/mmr.2019.10095. Epub 2019 Mar 27.
29 Whole-Exome Sequencing of Nasopharyngeal Carcinoma Families Reveals Novel Variants Potentially Involved in Nasopharyngeal Carcinoma.Sci Rep. 2019 Jul 9;9(1):9916. doi: 10.1038/s41598-019-46137-4.
30 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
31 Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
32 Breast cancer cells response to the antineoplastic agents cisplatin, carboplatin, and doxorubicin at the mRNA expression levels of distinct apoptosis-related genes, including the new member, BCL2L12. Ann N Y Acad Sci. 2007 Jan;1095:35-44. doi: 10.1196/annals.1397.005.
33 Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
34 Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
35 Effect of doxorubicin, oxaliplatin, and methotrexate administration on the transcriptional activity of BCL-2 family gene members in stomach cancer cells. Cancer Biol Ther. 2013 Jul;14(7):587-96. doi: 10.4161/cbt.24591. Epub 2013 May 10.
36 Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
37 Topotecan and methotrexate alter expression of the apoptosis-related genes BCL2, FAS and BCL2L12 in leukemic HL-60 cells. Biol Chem. 2006 Dec;387(12):1629-33. doi: 10.1515/BC.2006.203.
38 The effect of combination treatment with docosahexaenoic acid and 5-fluorouracil on the mRNA expression of apoptosis-related genes, including the novel gene BCL2L12, in gastric cancer cells. In Vitro Cell Dev Biol Anim. 2009 Jan-Feb;45(1-2):69-74. doi: 10.1007/s11626-008-9154-5. Epub 2008 Nov 18.
39 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.
40 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.
41 Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
42 A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
43 Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
44 Molecular signatures of cytotoxic effects in human embryonic kidney 293?cells treated with single and mixture of ochratoxin A and citrinin. Food Chem Toxicol. 2019 Jan;123:374-384. doi: 10.1016/j.fct.2018.11.015. Epub 2018 Nov 11.