Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2DH1SN)

• DOT Name: Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C)
• Synonyms: Protein FAM120C; Tumor antigen BJ-HCC-21
• Gene Name: FAM120C
• Related Disease:
  Syndromic X-linked intellectual disability Siderius type
  Autism spectrum disorder
  Kaposi sarcoma
  Pervasive developmental disorder
  Autism
• UniProt ID: F120C_HUMAN
• Sequence:
  MGVQGFQEFLEKRCPGAVVPVDLLKLARTVSRQQQQQHLHRQLPPTAALAPGAPRAARGS
  VPLQPPLPPAALGAYSGGAGPTRHHHPAHHFHHHGQAQPGLHPPLPPPPPPQLPGARVLV
  DAGSALPRLYGGYQTDWVCGGQWNAMLGYLSALCQACAYPGGDGLELVVMFPGGLGKDRL
  AEWGRRCQAERQTAQLIVGHVGNKGTPPPRAWFLPPACLSHCVRLALIRFRVKVFQSLED
  HHLEVVAFFRENGFHGLLAHDSEYALYNIPSYYSSHALKLSWNGKNLTTNQFLMQEVAKQ
  LGLKRMNFPIFAALLGNHILPDEDLAAFHWSLLGPEHPLASLKVRAHQLVLPPCDVVIKA
  VSEYVSSIKDPSNLDVVGKDVFKQSQSRTEDKIERFKKAVEYYSVTTKLSSLPVGPSFLG
  FRNNRLGNPPLPRNQVGTISAGKPMFSHQVPQKVKYPPPFPVGPNSSLLFSSHALGESHA
  FSEDPMLQNSPFANWAVSYDSSASQFPNYLPSKASPPLGPDSSHSSSSDGDEPNGASSDH
  ITEAFHHQPEWGNPNRDRGSWAQPVDTGVSEASLGDGEPHIPSLLSMSTRNHMDITIPPL
  PPVAPEVLRVAEHRHRRGLMYPYIYHVLTKGEIKIPVCIEDECNMELPPAALLFRSARQY
  VYGVLFSLAETQRKMERLAMRRRLPVEVPSVILKEWSAYKGKSPQTPELVSALTFREWTC
  PNLKKLWLGKAVEDKNRRMRAFLACMKSDTPSMLNPANVPTHLLLMCCVLRYMVQWPGGR
  ILHRHELDTFLAQAVSTQLYEPDRLQELKIEKLDARGIQLAALFMSGVDTALFANDACGQ
  PVPWEHCCPWIYFDGKLFQSKLIKAGRERVSLVELCDGQADLATKVEKMRQSILEGVNMN
  HPPPSALLPSPTFVPPMVPSLYPVSLYSRAMGSMPLPPQGRSRGFAGLHPIPPQGGKLEI
  AGMVVGQWAGSRSSRGRGSFGMQVVSVGGPGKGHGKEQTGRGSKGHKKGNKQGSSDGVSK
  SLELHQGRSRSQVNGNSGALIKEEKSDHRLPAPSQCALSRDSNECNNGNRYLPMNNREKN
  HLQEQKLETVAQRKED
• Tissue Specificity: Expressed at low levels in a number of tissues.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Syndromic X-linked intellectual disability Siderius type	DISN00RJ	Definitive	Genetic Variation	[1]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[2]
Kaposi sarcoma	DISC1H1Z	Strong	Altered Expression	[3]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[2]
Autism	DISV4V1Z	Limited	Biomarker	[2]

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 Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[8]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Constitutive coactivator of PPAR-gamma-like protein 2 (FAM120C).	[11]

References

• [1] Autism-associated familial microdeletion of Xp11.22.Clin Genet. 2008 Aug;74(2):134-44. doi: 10.1111/j.1399-0004.2008.01028.x. Epub 2008 May 21.
• [2] A complex Xp11.22 deletion in a patient with syndromic autism: exploration of FAM120C as a positional candidate gene for autism.Am J Med Genet A. 2014 Dec;164A(12):3035-41. doi: 10.1002/ajmg.a.36752. Epub 2014 Sep 24.
• [3] Kaposi's Sarcoma-Associated Herpesvirus ORF66 Is Essential for Late Gene Expression and Virus Production via Interaction with ORF34.J Virol. 2020 Jan 6;94(2):e01300-19. doi: 10.1128/JVI.01300-19. Print 2020 Jan 6.
• [4] 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.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [8] 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.
• [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] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [11] 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.