Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5PY5CY)

• DOT Name: Mitochondrial chaperone BCS1 (BCS1L)
• Synonyms: h-BCS1; BCS1-like protein
• Gene Name: BCS1L
• Related Disease:
  Bjornstad syndrome
  Delirium
  GRACILE syndrome
  Invasive breast carcinoma
  Male breast carcinoma
  Mental disorder
  Acute myelogenous leukaemia
  Advanced cancer
  Alzheimer disease
  Blast phase chronic myelogenous leukemia, BCR-ABL1 positive
  Breast cancer
  Breast carcinoma
  Chorioamnionitis
  Chromosomal disorder
  Epilepsy
  Fanconi's anemia
  HIV infectious disease
  Hypotrichosis
  Isolated congenital microcephaly
  Juvenile polyposis syndrome
  Lactic acidosis
  Leigh syndrome
  Major depressive disorder
  Mitochondrial complex III deficiency nuclear type 1
  Mitochondrial disease
  Myeloproliferative neoplasm
  Nervous system disease
  Non-insulin dependent diabetes
  Non-small-cell lung cancer
  Obesity
  Sensorineural hearing loss disorder
  Tuberculosis
  Wilms tumor
  Cholestasis
  Ductal breast carcinoma in situ
  Fetal growth restriction
  Movement disorder
  Neoplasm
  Osteoarthritis
  Rheumatoid arthritis
  Mitochondrial complex III deficiency
  Renal tubulopathy-encephalopathy-liver failure syndrome
  Colon adenocarcinoma
  Neuroblastoma
  Post-traumatic stress disorder
• UniProt ID: BCS1_HUMAN
• Pfam ID: PF00004 ; PF08740
• Sequence:
  MPLSDFILALKDNPYFGAGFGLVGVGTALALARKGVQLGLVAFRRHYMITLEVPARDRSY
  AWLLSWLTRHSTRTQHLSVETSYLQHESGRISTKFEFVPSPGNHFIWYRGKWIRVERSRE
  MQMIDLQTGTPWESVTFTALGTDRKVFFNILEEARELALQQEEGKTVMYTAVGSEWRPFG
  YPRRRRPLNSVVLQQGLADRIVRDVQEFIDNPKWYTDRGIPYRRGYLLYGPPGCGKSSFI
  TALAGELEHSICLLSLTDSSLSDDRLNHLLSVAPQQSLVLLEDVDAAFLSRDLAVENPVK
  YQGLGRLTFSGLLNALDGVASTEARIVFMTTNHVDRLDPALIRPGRVDLKEYVGYCSHWQ
  LTQMFQRFYPGQAPSLAENFAEHVLRATNQISPAQVQGYFMLYKNDPVGAIHNAESLRR
• Function: Chaperone necessary for the assembly of mitochondrial respiratory chain complex III. Plays an important role in the maintenance of mitochondrial tubular networks, respiratory chain assembly and formation of the LETM1 complex.
• Tissue Specificity: Ubiquitous.
• Reactome Pathway: Mitochondrial protein import (R-HSA-1268020)

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bjornstad syndrome	DISO267N	Definitive	Autosomal recessive	[1]
Delirium	DIS2OKP1	Definitive	Genetic Variation	[2]
GRACILE syndrome	DISU4K4N	Definitive	Autosomal recessive	[3]
Invasive breast carcinoma	DISANYTW	Definitive	Biomarker	[4]
Male breast carcinoma	DISUNQ2Q	Definitive	Biomarker	[5]
Mental disorder	DIS3J5R8	Definitive	Genetic Variation	[2]
Acute myelogenous leukaemia	DISCSPTN	Strong	Biomarker	[6]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[7]
Alzheimer disease	DISF8S70	Strong	Biomarker	[8]
Blast phase chronic myelogenous leukemia, BCR-ABL1 positive	DIS3KLUX	Strong	Biomarker	[9]
Breast cancer	DIS7DPX1	Strong	Biomarker	[10]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[10]
Chorioamnionitis	DISL1D9U	Strong	Biomarker	[11]
Chromosomal disorder	DISM5BB5	Strong	Biomarker	[12]
Epilepsy	DISBB28L	Strong	Biomarker	[13]
Fanconi's anemia	DISGW6Q8	Strong	Genetic Variation	[14]
HIV infectious disease	DISO97HC	Strong	Biomarker	[15]
Hypotrichosis	DISSW933	Strong	Genetic Variation	[16]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[14]
Juvenile polyposis syndrome	DISBPSLH	Strong	Genetic Variation	[17]
Lactic acidosis	DISZI1ZK	Strong	Genetic Variation	[14]
Leigh syndrome	DISWQU45	Strong	Autosomal recessive	[14]
Major depressive disorder	DIS4CL3X	Strong	Biomarker	[18]
Mitochondrial complex III deficiency nuclear type 1	DISTXS4G	Strong	Autosomal recessive	[19]
Mitochondrial disease	DISKAHA3	Strong	Biomarker	[20]
Myeloproliferative neoplasm	DIS5KAPA	Strong	Biomarker	[9]
Nervous system disease	DISJ7GGT	Strong	Genetic Variation	[21]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[22]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[23]
Obesity	DIS47Y1K	Strong	Biomarker	[24]
Sensorineural hearing loss disorder	DISJV45Z	Strong	Genetic Variation	[25]
Tuberculosis	DIS2YIMD	Strong	Biomarker	[26]
Wilms tumor	DISB6T16	Strong	Genetic Variation	[27]
Cholestasis	DISDJJWE	moderate	Biomarker	[3]
Ductal breast carcinoma in situ	DISLCJY7	moderate	Genetic Variation	[18]
Fetal growth restriction	DIS5WEJ5	moderate	Biomarker	[3]
Movement disorder	DISOJJ2D	moderate	Genetic Variation	[28]
Neoplasm	DISZKGEW	moderate	Altered Expression	[29]
Osteoarthritis	DIS05URM	moderate	Biomarker	[30]
Rheumatoid arthritis	DISTSB4J	moderate	Biomarker	[30]
Mitochondrial complex III deficiency	DISSUPJ6	Supportive	Autosomal recessive	[31]
Renal tubulopathy-encephalopathy-liver failure syndrome	DISZ3LPE	Supportive	Autosomal recessive	[32]
Colon adenocarcinoma	DISDRE0J	Limited	Biomarker	[33]
Neuroblastoma	DISVZBI4	Limited	Biomarker	[34]
Post-traumatic stress disorder	DISHL1EY	Limited	Biomarker	[35]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Mitochondrial chaperone BCS1 (BCS1L) affects the response to substance of Acetaminophen.	[41]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Mitochondrial chaperone BCS1 (BCS1L).	[36]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Mitochondrial chaperone BCS1 (BCS1L).	[37]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial chaperone BCS1 (BCS1L).	[38]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Mitochondrial chaperone BCS1 (BCS1L).	[39]
Coumestrol	DM40TBU	Investigative	Coumestrol increases the expression of Mitochondrial chaperone BCS1 (BCS1L).	[40]

References

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• [10] Impact of Awake Breast Cancer Surgery on Postoperative Lymphocyte Responses.In Vivo. 2019 Nov-Dec;33(6):1879-1884. doi: 10.21873/invivo.11681.
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• [17] Excellent Diagnostic Characteristics for Ultrafast Gene Profiling of DEFA1-IL1B-LTF in Detection of Prosthetic Joint Infections.J Clin Microbiol. 2017 Sep;55(9):2686-2697. doi: 10.1128/JCM.00558-17. Epub 2017 Jun 21.
• [18] Impact of pre-diagnosis depressive symptoms and health-related quality of life on treatment choice for ductal carcinoma in situ and stage I breast cancer in older women.Breast Cancer Res Treat. 2019 Feb;173(3):709-717. doi: 10.1007/s10549-018-5006-5. Epub 2018 Nov 8.
• [19] 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.
• [20] Molecular genetic investigations identify new clinical phenotypes associated with BCS1L-related mitochondrial disease.Hum Mol Genet. 2019 Nov 15;28(22):3766-3776. doi: 10.1093/hmg/ddz202.
• [21] Informing the training of health care professionals to implement behavior change strategies for physical activity promotion in neurorehabilitation: a systematic review.Transl Behav Med. 2020 Feb 3;10(1):310-323. doi: 10.1093/tbm/iby118.
• [22] Fabrication of Second Generation Smarter PLGA Based Nanocrystal Carriers for Improvement of Drug Delivery and Therapeutic Efficacy of Gliclazide in Type-2 Diabetes Rat Model.Sci Rep. 2019 Nov 22;9(1):17331. doi: 10.1038/s41598-019-53996-4.
• [23] PTD modified paclitaxel anti-resistant liposomes for treatment of drug-resistant non-small cell lung cancer.J Liposome Res. 2018 Sep;28(3):236-248. doi: 10.1080/08982104.2017.1327542. Epub 2017 May 24.
• [24] Laminar inflammatory events in lean and obese ponies subjected to high carbohydrate feeding: Implications for pasture-associated laminitis.Equine Vet J. 2015 Jul;47(4):489-93. doi: 10.1111/evj.12314. Epub 2014 Sep 10.
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• [26] Pharmaceutical salts of ethionamide with GRAS counter ion donors to enhance the solubility.Eur J Pharm Sci. 2017 Jan 1;96:578-589. doi: 10.1016/j.ejps.2016.10.035. Epub 2016 Nov 1.
• [27] WT1 mutation in pediatric patients with acute myeloid leukemia: a report from the Japanese Childhood AML Cooperative Study Group.Int J Hematol. 2013 Oct;98(4):437-45. doi: 10.1007/s12185-013-1409-6. Epub 2013 Aug 27.
• [28] Clinical and biochemical spectrum of mitochondrial complex III deficiency caused by mutations in the BCS1L gene.Clin Genet. 2009 Jun;75(6):585-7. doi: 10.1111/j.1399-0004.2009.01160.x.
• [29] The photocytotoxicity effect of cationic sulfonated corrole towards lung cancer cells: in vitro and in vivo study.Lasers Med Sci. 2019 Sep;34(7):1353-1363. doi: 10.1007/s10103-019-02725-4. Epub 2019 Feb 2.
• [30] Self nanoemulsifying granules (SNEGs) of meloxicam: preparation, characterization, molecular modeling and evaluation of in vivo anti-inflammatory activity.Drug Dev Ind Pharm. 2017 Apr;43(4):600-610. doi: 10.1080/03639045.2016.1275665. Epub 2017 Jan 17.
• [31] Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy. Hum Mol Genet. 2007 May 15;16(10):1241-52. doi: 10.1093/hmg/ddm072. Epub 2007 Apr 2.
• [32] A mutant mitochondrial respiratory chain assembly protein causes complex III deficiency in patients with tubulopathy, encephalopathy and liver failure. Nat Genet. 2001 Sep;29(1):57-60. doi: 10.1038/ng706.
• [33] Acquisition of resistance to butyrate enhances survival after stress and induces malignancy of human colon carcinoma cells.Cancer Res. 2004 Jul 1;64(13):4593-600. doi: 10.1158/0008-5472.CAN-04-0711.
• [34] Tat-PTD-modified oncolytic adenovirus driven by the SCG3 promoter and ASH1 enhancer for neuroblastoma therapy.Hum Gene Ther. 2013 Aug;24(8):766-75. doi: 10.1089/hum.2012.132.
• [35] The Relationship Between Posttraumatic Stress Disorder Symptoms and Posttraumatic Growth Among HIV-Infected Men Who Have Sex With Men in Beijing, China: The Mediating Roles of Coping Strategies.Front Psychol. 2018 Sep 27;9:1787. doi: 10.3389/fpsyg.2018.01787. eCollection 2018.
• [36] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [37] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [38] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [41] Interindividual variation in gene expression responses and metabolite formation in acetaminophen-exposed primary human hepatocytes. Arch Toxicol. 2016 May;90(5):1103-15. doi: 10.1007/s00204-015-1545-2. Epub 2015 Jun 24.