Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGJ5WUF)

• DOT Name: Zinc finger protein basonuclin-1 (BNC1)
• Gene Name: BNC1
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Breast cancer
  Breast carcinoma
  Childhood acute lymphoblastic leukemia
  Clear cell renal carcinoma
  Female hypogonadism
  Hepatocellular carcinoma
  Neoplasm
  Renal cell carcinoma
  Squamous cell carcinoma
  46 XX gonadal dysgenesis
  Pancreatic cancer
  Premature ovarian failure 16
• UniProt ID: BNC1_HUMAN
• Pfam ID: PF12874
• Sequence:
  MRRRPPSRGGRGAARARETRRQPRHRSGRRMAEAISCTLNCSCQSFKPGKINHRQCDQCK
  HGWVAHALSKLRIPPMYPTSQVEIVQSNVVFDISSLMLYGTQAIPVRLKILLDRLFSVLK
  QDEVLQILHALDWTLQDYIRGYVLQDASGKVLDHWSIMTSEEEVATLQQFLRFGETKSIV
  ELMAIQEKEEQSIIIPPSTANVDIRAFIESCSHRSSSLPTPVDKGNPSSIHPFENLISNM
  TFMLPFQFFNPLPPALIGSLPEQYMLEQGHDQSQDPKQEVHGPFPDSSFLTSSSTPFQVE
  KDQCLNCPDAITKKEDSTHLSDSSSYNIVTKFERTQLSPEAKVKPERNSLGTKKGRVFCT
  ACEKTFYDKGTLKIHYNAVHLKIKHKCTIEGCNMVFSSLRSRNRHSANPNPRLHMPMNRN
  NRDKDLRNSLNLASSENYKCPGFTVTSPDCRPPPSYPGSGEDSKGQPAFPNIGQNGVLFP
  NLKTVQPVLPFYRSPATPAEVANTPGILPSLPLLSSSIPEQLISNEMPFDALPKKKSRKS
  SMPIKIEKEAVEIANEKRHNLSSDEDMPLQVVSEDEQEACSPQSHRVSEEQHVQSGGLGK
  PFPEGERPCHRESVIESSGAISQTPEQATHNSERETEQTPALIMVPREVEDGGHEHYFTP
  GMEPQVPFSDYMELQQRLLAGGLFSALSNRGMAFPCLEDSKELEHVGQHALARQIEENRF
  QCDICKKTFKNACSVKIHHKNMHVKEMHTCTVEGCNATFPSRRSRDRHSSNLNLHQKALS
  QEALESSEDHFRAAYLLKDVAKEAYQDVAFTQQASQTSVIFKGTSRMGSLVYPITQVHSA
  SLESYNSGPLSEGTILDLSTTSSMKSESSSHSSWDSDGVSEEGTVLMEDSDGNCEGSSLV
  PGEDEYPICVLMEKADQSLASLPSGLPITCHLCQKTYSNKGTFRAHYKTVHLRQLHKCKV
  PGCNTMFSSVRSRNRHSQNPNLHKSLASSPSHLQ
• Function: Transcriptional activator. It is likely involved in the regulation of keratinocytes terminal differentiation in squamous epithelia and hair follicles. Required for the maintenance of spermatogenesis. It is involved in the positive regulation of oocyte maturation, probably acting through the control of BMP15 levels and regulation of AKT signaling cascade. May also play a role in the early development of embryos.
• Tissue Specificity: In epidermis, primarily detected in cells of the basal or immediately suprabasal layers (at protein level) . In hair follicles, mainly expressed in the outer root sheath (at protein level) . Expressed in epidermis, testis and foreskin, and to a lower extent in thymus, spleen, mammary glands, placenta, brain and heart . Expressed in the ovary, notably in oocytes .

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Breast cancer	DIS7DPX1	Strong	Biomarker	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[3]
Childhood acute lymphoblastic leukemia	DISJ5D6U	Strong	Biomarker	[4]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[5]
Female hypogonadism	DISWASB4	Strong	Genetic Variation	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[7]
Neoplasm	DISZKGEW	Strong	Biomarker	[8]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[5]
Squamous cell carcinoma	DISQVIFL	Strong	Altered Expression	[1]
46 XX gonadal dysgenesis	DISBB9HA	Supportive	Autosomal dominant	[6]
Pancreatic cancer	DISJC981	Limited	Biomarker	[8]
Premature ovarian failure 16	DISVLGB3	Limited	Unknown	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Zinc finger protein basonuclin-1 (BNC1) affects the response to substance of Doxorubicin.	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Zinc finger protein basonuclin-1 (BNC1).	[10]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Zinc finger protein basonuclin-1 (BNC1).	[11]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Zinc finger protein basonuclin-1 (BNC1).	[12]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Zinc finger protein basonuclin-1 (BNC1).	[13]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Zinc finger protein basonuclin-1 (BNC1).	[14]
Cytarabine	DMZD5QR	Approved	Cytarabine decreases the expression of Zinc finger protein basonuclin-1 (BNC1).	[16]
Amphotericin B	DMTAJQE	Approved	Amphotericin B increases the expression of Zinc finger protein basonuclin-1 (BNC1).	[17]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Zinc finger protein basonuclin-1 (BNC1).	[19]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Zinc finger protein basonuclin-1 (BNC1).	[20]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Fulvestrant	DM0YZC6	Approved	Fulvestrant decreases the methylation of Zinc finger protein basonuclin-1 (BNC1).	[15]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Zinc finger protein basonuclin-1 (BNC1).	[18]

References

• [1] p63 Transcriptionally regulates BNC1, a Pol I and Pol II transcription factor that regulates ribosomal biogenesis and epithelial differentiation.Eur J Cancer. 2012 Jun;48(9):1401-6. doi: 10.1016/j.ejca.2011.06.032. Epub 2011 Jul 7.
• [2] A Novel Small Molecule Modulator of Amyloid Pathology.J Alzheimers Dis. 2016 May 4;53(1):273-87. doi: 10.3233/JAD-151160.
• [3] A comparison of folic acid deficiency-induced genomic instability in lymphocytes of breast cancer patients and normal non-cancer controls from a Chinese population in Yunnan.Mutagenesis. 2006 Jan;21(1):41-7. doi: 10.1093/mutage/gei069. Epub 2005 Dec 8.
• [4] Epigenetic analysis of childhood acute lymphoblastic leukemia.Epigenetics. 2009 Apr 1;4(3):185-93. doi: 10.4161/epi.4.3.8752. Epub 2009 Apr 12.
• [5] Identification of candidate tumour suppressor genes frequently methylated in renal cell carcinoma.Oncogene. 2010 Apr 8;29(14):2104-17. doi: 10.1038/onc.2009.493. Epub 2010 Feb 15.
• [6] Basonuclin 1 deficiency is a cause of primary ovarian insufficiency. Hum Mol Genet. 2018 Nov 1;27(21):3787-3800. doi: 10.1093/hmg/ddy261.
• [7] Decreased Expression of BNC1 and BNC2 Is Associated with Genetic or Epigenetic Regulation in Hepatocellular Carcinoma.Int J Mol Sci. 2016 Jan 25;17(2):153. doi: 10.3390/ijms17020153.
• [8] Promoter methylation of ADAMTS1 and BNC1 as potential biomarkers for early detection of pancreatic cancer in blood.Clin Epigenetics. 2019 Apr 5;11(1):59. doi: 10.1186/s13148-019-0650-0.
• [9] De novo copy number variants are associated with congenital diaphragmatic hernia. J Med Genet. 2012 Oct;49(10):650-9. doi: 10.1136/jmedgenet-2012-101135.
• [10] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [11] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [12] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [13] A genome-wide screen for promoter methylation in lung cancer identifies novel methylation markers for multiple malignancies. PLoS Med. 2006 Dec;3(12):e486. doi: 10.1371/journal.pmed.0030486.
• [14] 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.
• [15] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [16] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [17] Differential expression of microRNAs and their predicted targets in renal cells exposed to amphotericin B and its complex with copper (II) ions. Toxicol Mech Methods. 2017 Sep;27(7):537-543. doi: 10.1080/15376516.2017.1333554. Epub 2017 Jun 8.
• [18] 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.
• [19] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [20] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [21] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.