Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTM46L89)

• DOT Name: Transmembrane protein 218 (TMEM218)
• Gene Name: TMEM218
• Related Disease:
  Joubert syndrome 39
  Medullary sponge kidney
  Nephronophthisis
  Senior-Loken syndrome
  Senior-Loken syndrome 4
  Senior-Loken syndrome 5
  Senior-Loken syndrome 7
• UniProt ID: TM218_HUMAN
• Sequence:
  MAGTVLGVGAGVFILALLWVAVLLLCVLLSRASGAARFSVIFLFFGAVIITSVLLLFPRA
  GEFPAPEVEVKIVDDFFIGRYVLLAFLSAIFLGGLFLVLIHYVLEPIYAKPLHSY
• Function: May be involved in ciliary biogenesis or function.

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Joubert syndrome 39	DISIUBWI	Strong	Autosomal recessive	[1]
Medullary sponge kidney	DISA0949	Strong	Biomarker	[1]
Nephronophthisis	DISXU4HY	Strong	Biomarker	[1]
Senior-Loken syndrome	DISGBSGP	Strong	Biomarker	[1]
Senior-Loken syndrome 4	DISRY70P	Strong	Biomarker	[1]
Senior-Loken syndrome 5	DISAQTI0	Strong	Biomarker	[1]
Senior-Loken syndrome 7	DISJOZC5	Strong	Biomarker	[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 218 (TMEM218).	[2]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Transmembrane protein 218 (TMEM218).	[5]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Transmembrane protein 218 (TMEM218).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 218 (TMEM218).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 218 (TMEM218).	[4]
Panobinostat	DM58WKG	Approved	Panobinostat decreases the expression of Transmembrane protein 218 (TMEM218).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Transmembrane protein 218 (TMEM218).	[7]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Transmembrane protein 218 (TMEM218).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Transmembrane protein 218 (TMEM218).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Transmembrane protein 218 (TMEM218).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Transmembrane protein 218 (TMEM218).	[11]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Transmembrane protein 218 (TMEM218).	[12]

References

• [1] Nephronophthisis and retinal degeneration in tmem218-/- mice: a novel mouse model for Senior-L?ken syndrome?. Vet Pathol. 2015 May;52(3):580-95. doi: 10.1177/0300985814547392. Epub 2014 Aug 26.
• [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] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] 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.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [10] Cystathionine metabolic enzymes play a role in the inflammation resolution of human keratinocytes in response to sub-cytotoxic formaldehyde exposure. Toxicol Appl Pharmacol. 2016 Nov 1;310:185-194.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.