Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRD9AUH)

• DOT Name: Protein FAM222A (FAM222A)
• Gene Name: FAM222A
• Related Disease: Major depressive disorder
• UniProt ID: F222A_HUMAN
• Pfam ID: PF15258
• Sequence:
  MLACLQRTQNAPGQHLACPSKSLELRKCEAVASAMHSSRYPSPAELDAYAEKVANSPLSI
  KIFPTNIRVPQHKHLSRTVNGYDTSGQRYSPYPQHTAGYQGLLAIVKAAVSSSSTAAPAG
  PAKSVLKSAEGKRTKLSPAAVQVGIAPYPVPSTLGPLAYPKPPEAPAPPPGLPAAATAAS
  VIPLPGRGLPLPPSNLPSIHSLLYQLNQQCQAPGAAPPACQGMAIPHPSPAKHGPVPSFP
  SMAYSAAAGLPDCRKGTELGQGATQALTLAGAAKPAGYADSGLDYLLWPQKPPPPPPQPL
  RAYSGSTVASKSPEACGGRAYERASGSPLNCGVGLPTSFTVGQYFAAPWNSVLVTPTSDC
  YNPAAAVVVTELGPGAARELAGPPADALSGLPSKSVCNTSVLSSSLQSLEYLINDIRPPC
  IKEQMLGKGYETVAVPRLLDHQHAHIRLPVYR

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[1]

1 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 FAM222A (FAM222A).	[2]

15 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 Protein FAM222A (FAM222A).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Protein FAM222A (FAM222A).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein FAM222A (FAM222A).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein FAM222A (FAM222A).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein FAM222A (FAM222A).	[7]
Estradiol	DMUNTE3	Approved	Estradiol increases the expression of Protein FAM222A (FAM222A).	[8]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Protein FAM222A (FAM222A).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Protein FAM222A (FAM222A).	[10]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Protein FAM222A (FAM222A).	[11]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Protein FAM222A (FAM222A).	[12]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Protein FAM222A (FAM222A).	[13]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Protein FAM222A (FAM222A).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein FAM222A (FAM222A).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Protein FAM222A (FAM222A).	[15]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Protein FAM222A (FAM222A).	[16]

References

• [1] GWAS and systems biology analysis of depressive symptoms among smokers from the COPDGene cohort.J Affect Disord. 2019 Jan 15;243:16-22. doi: 10.1016/j.jad.2018.09.003. Epub 2018 Sep 7.
• [2] 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.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [5] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [6] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] 17-Estradiol Activates HSF1 via MAPK Signaling in ER-Positive Breast Cancer Cells. Cancers (Basel). 2019 Oct 11;11(10):1533. doi: 10.3390/cancers11101533.
• [9] 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.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [12] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [13] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [14] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [15] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.
• [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.