Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLYN2T1)

• DOT Name: Protein FAM110B (FAM110B)
• Gene Name: FAM110B
• Related Disease:
  Castration-resistant prostate carcinoma
  Herpes zoster
  Prostate cancer
  Prostate carcinoma
  Neoplasm
• UniProt ID: F110B_HUMAN
• Pfam ID: PF14160 ; PF14161
• Sequence:
  MPTETLQTGSMVKPVSPAGTFTSAVPLRILNKGPDYFRRQAEPNPKRLSAVERLEADKAK
  YVKSQEVINAKQEPVKPAVLAKPPVCPAAKRALGSPTLKVFGNHAKTESGVQRENLKLEI
  LKNIINSSEGSSSGSGHKHSSRNWPPHRSEATDLHRHSFAESLKVYPTQGRRSPQEGGSH
  VGRRLLEQSAESFLHVSHSSSDIRKVTSVKPLKAIPCSSSAPPLPPKPKIAAIASMKSPE
  ADPVEPACGVSRRPSLQRSKSDLSDRYFRVDADVERFFNYCGLDPEELENLGMENFARAN
  SDIISLNFRSASMISSDCEQSQDSNSDLRNDDSANDRVPYGISAIERNARIIKWLYSIKQ
  ARESQKVSHV
• Function: May be involved in tumor progression.
• Tissue Specificity: Detected in thyroid, spleen and testis, and at lower levels in stomach, spinal cord, lymph node, trachea, adrenal gland, prostate, ovary and intestine.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Castration-resistant prostate carcinoma	DISVGAE6	moderate	Biomarker	[1]
Herpes zoster	DISNSMNY	moderate	Genetic Variation	[2]
Prostate cancer	DISF190Y	moderate	Altered Expression	[1]
Prostate carcinoma	DISMJPLE	moderate	Altered Expression	[1]
Neoplasm	DISZKGEW	Limited	Altered Expression	[3]

14 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 Protein FAM110B (FAM110B).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Protein FAM110B (FAM110B).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein FAM110B (FAM110B).	[6]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein FAM110B (FAM110B).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Protein FAM110B (FAM110B).	[8]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Protein FAM110B (FAM110B).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein FAM110B (FAM110B).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Protein FAM110B (FAM110B).	[11]
Melphalan	DMOLNHF	Approved	Melphalan decreases the expression of Protein FAM110B (FAM110B).	[12]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Protein FAM110B (FAM110B).	[13]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide increases the expression of Protein FAM110B (FAM110B).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Protein FAM110B (FAM110B).	[16]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein FAM110B (FAM110B).	[17]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Protein FAM110B (FAM110B).	[18]

1 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 increases the methylation of Protein FAM110B (FAM110B).	[14]

References

• [1] Integrative genomic, transcriptomic, and RNAi analysis indicates a potential oncogenic role for FAM110B in castration-resistant prostate cancer.Prostate. 2012 May 15;72(7):789-802. doi: 10.1002/pros.21487. Epub 2011 Sep 14.
• [2] The eMERGE genotype set of 83,717 subjects imputed to ~40million variants genome wide and association with the herpes zoster medical record phenotype.Genet Epidemiol. 2019 Feb;43(1):63-81. doi: 10.1002/gepi.22167. Epub 2018 Oct 8.
• [3] Integrated analysis of tumor differentiation genes in pancreatic adenocarcinoma.PLoS One. 2018 Mar 29;13(3):e0193427. doi: 10.1371/journal.pone.0193427. eCollection 2018.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [6] 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.
• [7] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Long-term estrogen exposure promotes carcinogen bioactivation, induces persistent changes in gene expression, and enhances the tumorigenicity of MCF-7 human breast cancer cells. Toxicol Appl Pharmacol. 2009 Nov 1;240(3):355-66.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Arsenic suppresses gene expression in promyelocytic leukemia cells partly through Sp1 oxidation. Blood. 2005 Jul 1;106(1):304-10.
• [12] Bone marrow osteoblast damage by chemotherapeutic agents. PLoS One. 2012;7(2):e30758. doi: 10.1371/journal.pone.0030758. Epub 2012 Feb 17.
• [13] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [14] 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.
• [15] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [16] 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.
• [17] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [18] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.