Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN0SF11)

• DOT Name: Protein FAM83H (FAM83H)
• Gene Name: FAM83H
• Related Disease:
  Bone osteosarcoma
  Osteosarcoma
  Advanced cancer
  Amelogenesis imperfecta
  Amelogenesis imperfecta, type 3A
  Carcinoma of liver and intrahepatic biliary tract
  Cervical cancer
  Cervical carcinoma
  Colorectal carcinoma
  Hepatocellular carcinoma
  Liver cancer
  Neoplasm
  Kidney cancer
  Renal carcinoma
  Renal cell carcinoma
  Patent ductus arteriosus
• UniProt ID: FA83H_HUMAN
• Pfam ID: PF07894
• Sequence:
  MARRSQSSSQGDNPLAPGYLPPHYKEYYRLAVDALAEGGSEAYSRFLATEGAPDFLCPEE
  LEHVSRHLRPPQYVTREPPEGSLLDVDMDGSSGTYWPVNSDQAVPELDLGWPLTFGFQGT
  EVTTLVQPPPPDSPSIKDEARRMIRSAQQVVAVVMDMFTDVDLLSEVLEAAARRVPVYIL
  LDEMNAQHFLDMADKCRVNLQHVDFLRVRTVAGPTYYCRTGKSFKGHVKEKFLLVDCAVV
  MSGSYSFMWSFEKIHRSLAHVFQGELVSSFDEEFRILFAQSEPLVPSAAALARMDAYALA
  PYAGAGPLVGVPGVGAPTPFSFPKRAHLLFPPPREEGLGFPSFLDPDRHFLSAFRREEPP
  RMPGGALEPHAGLRPLSRRLEAEAGPAGELAGARGFFQARHLEMDAFKRHSFATEGAGAV
  ENFAAARQVSRQTFLSHGDDFRFQTSHFHRDQLYQQQYQWDPQLTPARPQGLFEKLRGGR
  AGFADPDDFTLGAGPRFPELGPDGHQRLDYVPSSASREVRHGSDPAFAPGPRGLEPSGAP
  RPNLTQRFPCQAAARPGPDPAPEAEPERRGGPEGRAGLRRWRLASYLSGCHGEDGGDDGL
  PAPMEAEAYEDDVLAPGGRAPAGDLLPSAFRVPAAFPTKVPVPGPGSGGNGPEREGPEEP
  GLAKQDSFRSRLNPLVQRSSRLRSSLIFSTSQAEGAAGAAAATEKVQLLHKEQTVSETLG
  PGGEAVRSAASTKVAELLEKYKGPARDPGGGAGAITVASHSKAVVSQAWREEVAAPGAVG
  GERRSLESCLLDLRDSFAQQLHQEAERQPGAASLTAAQLLDTLGRSGSDRLPSRFLSAQS
  HSTSPQGLDSPLPLEGSGAHQVLHNESKGSPTSAYPERKGSPTPGFSTRRGSPTTGFIEQ
  KGSPTSAYPERRGSPVPPVPERRSSPVPPVPERRGSLTLTISGESPKAGPAEEGPSGPME
  VLRKGSLRLRQLLSPKGERRMEDEGGFPVPQENGQPESPRRLSLGQGDSTEAATEERGPR
  ARLSSATANALYSSNLRDDTKAILEQISAHGQKHRAVPAPSPGPTHNSPELGRPPAAGVL
  APDMSDKDKCSAIFRSDSLGTQGRLSRTLPASAEERDRLLRRMESMRKEKRVYSRFEVFC
  KKEEASSPGAGEGPAEEGTRDSKVGKFVPKILGTFKSKK
• Function: May play a major role in the structural organization and calcification of developing enamel. May play a role in keratin cytoskeleton disassembly by recruiting CSNK1A1 to keratin filaments. Thereby, it may regulate epithelial cell migration.
• Tissue Specificity: Expressed in the tooth follicle.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Bone osteosarcoma	DIST1004	Definitive	Altered Expression	[1]
Osteosarcoma	DISLQ7E2	Definitive	Altered Expression	[1]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[2]
Amelogenesis imperfecta	DISGYR9E	Strong	Altered Expression	[3]
Amelogenesis imperfecta, type 3A	DISP3OJG	Strong	Autosomal dominant	[4]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Strong	Biomarker	[5]
Cervical cancer	DISFSHPF	Strong	Altered Expression	[2]
Cervical carcinoma	DIST4S00	Strong	Altered Expression	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[6]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[5]
Liver cancer	DISDE4BI	Strong	Biomarker	[5]
Neoplasm	DISZKGEW	Strong	Altered Expression	[2]
Kidney cancer	DISBIPKM	moderate	Biomarker	[7]
Renal carcinoma	DISER9XT	moderate	Biomarker	[7]
Renal cell carcinoma	DISQZ2X8	moderate	Altered Expression	[7]
Patent ductus arteriosus	DIS9P8YS	Limited	Altered Expression	[8]

5 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 FAM83H (FAM83H).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Protein FAM83H (FAM83H).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Protein FAM83H (FAM83H).	[15]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Protein FAM83H (FAM83H).	[17]
Coumarin	DM0N8ZM	Investigative	Coumarin affects the phosphorylation of Protein FAM83H (FAM83H).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein FAM83H (FAM83H).	[10]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Protein FAM83H (FAM83H).	[12]
Liothyronine	DM6IR3P	Approved	Liothyronine increases the expression of Protein FAM83H (FAM83H).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein FAM83H (FAM83H).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein FAM83H (FAM83H).	[16]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Protein FAM83H (FAM83H).	[18]

References

• [1] FAM83H is involved in stabilization of -catenin and progression of osteosarcomas.J Exp Clin Cancer Res. 2019 Jun 18;38(1):267. doi: 10.1186/s13046-019-1274-0.
• [2] Family with Sequence Similarity 83 Member H Promotes the Viability and Metastasis of Cervical Cancer Cells and Indicates a Poor Prognosis.Yonsei Med J. 2019 Jul;60(7):611-618. doi: 10.3349/ymj.2019.60.7.611.
• [3] Immunohistochemical Localization of Fam83h During Fluorosis-induced Mouse Molar Development.J Histochem Cytochem. 2018 Sep;66(9):663-671. doi: 10.1369/0022155418772289. Epub 2018 Apr 20.
• [4] FAM83H mutations in families with autosomal-dominant hypocalcified amelogenesis imperfecta. Am J Hum Genet. 2008 Feb;82(2):489-94. doi: 10.1016/j.ajhg.2007.09.020.
• [5] FAM83H is involved in the progression of hepatocellular carcinoma and is regulated by MYC.Sci Rep. 2017 Jun 12;7(1):3274. doi: 10.1038/s41598-017-03639-3.
• [6] A novel mechanism of keratin cytoskeleton organization through casein kinase I and FAM83H in colorectal cancer.J Cell Sci. 2013 Oct 15;126(Pt 20):4721-31. doi: 10.1242/jcs.129684. Epub 2013 Jul 31.
• [7] The Expression Patterns of FAM83H and PANX2 Are Associated With Shorter Survival of Clear Cell Renal Cell Carcinoma Patients.Front Oncol. 2019 Jan 22;9:14. doi: 10.3389/fonc.2019.00014. eCollection 2019.
• [8] Comprehensive characterisation of compartment-specific long non-coding RNAs associated with pancreatic ductal adenocarcinoma.Gut. 2019 Mar;68(3):499-511. doi: 10.1136/gutjnl-2017-314353. Epub 2018 Feb 10.
• [9] 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.
• [10] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [11] 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.
• [12] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [13] Monitoring of deiodinase deficiency based on transcriptomic responses in SH-SY5Y cells. Arch Toxicol. 2013 Jun;87(6):1103-13. doi: 10.1007/s00204-013-1018-4. Epub 2013 Feb 10.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] 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.
• [16] 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.
• [17] 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.
• [18] Characterization of the Molecular Alterations Induced by the Prolonged Exposure of Normal Colon Mucosa and Colon Cancer Cells to Low-Dose Bisphenol A. Int J Mol Sci. 2022 Oct 1;23(19):11620. doi: 10.3390/ijms231911620.