Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNF4CR7)

• DOT Name: Transmembrane protein 138 (TMEM138)
• Gene Name: TMEM138
• Related Disease:
  Joubert syndrome 16
  Ciliopathy
  Joubert syndrome with oculorenal defect
  Joubert syndrome
• UniProt ID: TM138_HUMAN
• Pfam ID: PF14935
• Sequence:
  MLQTSNYSLVLSLQFLLLSYDLFVNSFSELLQKTPVIQLVLFIIQDIAVLFNIIIIFLMF
  FNTFVFQAGLVNLLFHKFKGTIILTAVYFALSISLHVWVMNLRWKNSNSFIWTDGLQMLF
  VFQRLAAVLYCYFYKRTAVRLGDPHFYQDSLWLRKEFMQVRR
• Function: Required for ciliogenesis.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Joubert syndrome 16	DIS7K1LK	Strong	Autosomal recessive	[1]
Ciliopathy	DIS10G4I	Moderate	Autosomal recessive	[2]
Joubert syndrome with oculorenal defect	DISU0IPO	Supportive	Autosomal recessive	[1]
Joubert syndrome	DIS7P5CO	Limited	Biomarker	[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 Transmembrane protein 138 (TMEM138).	[3]

9 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 Transmembrane protein 138 (TMEM138).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 138 (TMEM138).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Transmembrane protein 138 (TMEM138).	[6]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Transmembrane protein 138 (TMEM138).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Transmembrane protein 138 (TMEM138).	[8]
GSK2110183	DMZHB37	Phase 2	GSK2110183 decreases the expression of Transmembrane protein 138 (TMEM138).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Transmembrane protein 138 (TMEM138).	[10]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Transmembrane protein 138 (TMEM138).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Transmembrane protein 138 (TMEM138).	[12]

References

• [1] Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science. 2012 Feb 24;335(6071):966-9. doi: 10.1126/science.1213506. Epub 2012 Jan 26.
• [2] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [3] 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.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] 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.
• [8] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [9] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [10] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] 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.