Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWFLPK2)

• DOT Name: Transmembrane protein 222 (TMEM222)
• Gene Name: TMEM222
• Related Disease: Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities
• UniProt ID: TM222_HUMAN
• Pfam ID: PF05608
• Sequence:
  MAEAEGSSLLLLPPPPPPPRMAEVEAPTAAETDMKQYQGSGGVAMDVERSRFPYCVVWTP
  IPVLTWFFPIIGHMGICTSTGVIRDFAGPYFVSEDNMAFGKPAKYWKLDPAQVYASGPNA
  WDTAVHDASEEYKHRMHNLCCDNCHSHVALALNLMRYNNSTNWNMVTLCFFCLLYGKYVS
  VGAFVKTWLPFILLLGIILTVSLVFNLR
• Tissue Specificity: Widely expressed. The highest expression is observed in the brain.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neurodevelopmental disorder with motor and speech delay and behavioral abnormalities	DISTCF37	Strong	Autosomal recessive	[1]

3 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 Transmembrane protein 222 (TMEM222).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Transmembrane protein 222 (TMEM222).	[8]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 decreases the phosphorylation of Transmembrane protein 222 (TMEM222).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Transmembrane protein 222 (TMEM222).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Transmembrane protein 222 (TMEM222).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Transmembrane protein 222 (TMEM222).	[3]
Selenium	DM25CGV	Approved	Selenium increases the expression of Transmembrane protein 222 (TMEM222).	[5]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Transmembrane protein 222 (TMEM222).	[6]
Nicotine	DMWX5CO	Approved	Nicotine increases the splicing of Transmembrane protein 222 (TMEM222).	[7]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol increases the expression of Transmembrane protein 222 (TMEM222).	[5]

References

• [1] Biallelic variants in TMEM222 cause a new autosomal recessive neurodevelopmental disorder. Genet Med. 2021 Jul;23(7):1246-1254. doi: 10.1038/s41436-021-01133-w. Epub 2021 Apr 6.
• [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] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [4] 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.
• [5] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [6] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [7] Characterizing the genetic basis for nicotine induced cancer development: a transcriptome sequencing study. PLoS One. 2013 Jun 18;8(6):e67252.
• [8] 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.
• [9] 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.