Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5FAEJJ)

• DOT Name: Protein boule-like (BOLL)
• Gene Name: BOLL
• Related Disease:
  Hypogonadism, male
  Male infertility
  Oligospermia
  Prostate cancer
  Colorectal carcinoma
  Colorectal neoplasm
  Adenocarcinoma
• UniProt ID: BOLL_HUMAN
• Pfam ID: PF00076
• Sequence:
  MQTDSLSPSPNPVSPVPLNNPTSAPRYGTVIPNRIFVGGIDFKTNESDLRKFFSQYGSVK
  EVKIVNDRAGVSKGYGFVTFETQEDAQKILQEAEKLNYKDKKLNIGPAIRKQQVGIPRSS
  IMPAAGTMYLTTSTGYPYTYHNGVAYFHTPEVTSVPPPWPSRSVCSSPVMVAQPIYQQPA
  YHYQATTQYLPGQWQWSVPQPSASSAPFLYLQPSEVIYQPVEIAQDGGCVPPPLSLMETS
  VPEPYSDHGVQATYHQVYAPSAITMPAPVMQPEPIKTVWSIHY
• Function: Probable RNA-binding protein, which may be required during spermatogenesis. May act by binding to the 3'-UTR of mRNAs and regulating their translation.
• Tissue Specificity: Testis specific. Not expressed in early embryos, primordial germ cells and spermatogonial cells. First expressed in the cytoplasm of spermatocytes and then persists through meiosis.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hypogonadism, male	DISV1F5R	Strong	Altered Expression	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Oligospermia	DIS6YJF3	Strong	Posttranslational Modification	[3]
Prostate cancer	DISF190Y	Strong	Genetic Variation	[4]
Colorectal carcinoma	DIS5PYL0	Disputed	Biomarker	[5]
Colorectal neoplasm	DISR1UCN	Disputed	Biomarker	[5]
Adenocarcinoma	DIS3IHTY	Limited	Biomarker	[6]

2 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 Protein boule-like (BOLL).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein boule-like (BOLL).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Amiodarone	DMUTEX3	Phase 2/3 Trial	Amiodarone increases the expression of Protein boule-like (BOLL).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein boule-like (BOLL).	[10]

References

• [1] Messenger RNA transcripts of the meiotic regulator BOULE in the testis of azoospermic men and their application in predicting the success of sperm retrieval.Hum Reprod. 2005 Mar;20(3):782-8. doi: 10.1093/humrep/deh647. Epub 2004 Dec 9.
• [2] Posttranscriptional regulation of CDC25A by BOLL is a conserved fertility mechanism essential for human spermatogenesis.J Clin Endocrinol Metab. 2009 Jul;94(7):2650-7. doi: 10.1210/jc.2009-0108. Epub 2009 May 5.
• [3] Causes and Clinical Features of Infertile Men With Nonobstructive Azoospermia and Histopathologic Diagnosis of Hypospermatogenesis.Urology. 2017 Jul;105:62-68. doi: 10.1016/j.urology.2017.03.026. Epub 2017 Mar 22.
• [4] Evaluating genetic risk for prostate cancer among Japanese and Latinos.Cancer Epidemiol Biomarkers Prev. 2012 Nov;21(11):2048-58. doi: 10.1158/1055-9965.EPI-12-0598. Epub 2012 Aug 24.
• [5] Comparing the DNA hypermethylome with gene mutations in human colorectal cancer.PLoS Genet. 2007 Sep;3(9):1709-23. doi: 10.1371/journal.pgen.0030157. Epub 2007 Jul 31.
• [6] Concomitant promoter methylation of multiple genes in lung adenocarcinomas from current, former and never smokers.Carcinogenesis. 2009 Jul;30(7):1132-8. doi: 10.1093/carcin/bgp114. Epub 2009 May 12.
• [7] 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.
• [8] Identification by automated screening of a small molecule that selectively eliminates neural stem cells derived from hESCs but not dopamine neurons. PLoS One. 2009 Sep 23;4(9):e7155.
• [9] 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.
• [10] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.