Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRT51D9)

• DOT Name: Transmembrane protein 39A (TMEM39A)
• Gene Name: TMEM39A
• Related Disease:
  Primary biliary cholangitis
  Systemic lupus erythematosus
• UniProt ID: TM39A_HUMAN
• Pfam ID: PF10271
• Sequence:
  MPGGRRGPSRQQLSRSALPSLQTLVGGGCGNGTGLRNRNGSAIGLPVPPITALITPGPVR
  HCQIPDLPVDGSLLFEFLFFIYLLVALFIQYINIYKTVWWYPYNHPASCTSLNFHLIDYH
  LAAFITVMLARRLVWALISEATKAGAASMIHYMVLISARLVLLTLCGWVLCWTLVNLFRS
  HSVLNLLFLGYPFGVYVPLCCFHQDSRAHLLLTDYNYVVQHEAVEESASTVGGLAKSKDF
  LSLLLESLKEQFNNATPIPTHSCPLSPDLIRNEVECLKADFNHRIKEVLFNSLFSAYYVA
  FLPLCFVKSTQYYDMRWSCEHLIMVWINAFVMLTTQLLPSKYCDLLHKSAAHLGKWQKLE
  HGSYSNAPQHIWSENTIWPQGVLVRHSRCLYRAMGPYNVAVPSDVSHARFYFLFHRPLRL
  LNLLILIEGSVVFYQLYSLLRSEKWNHTLSMALILFCNYYVLFKLLRDRIVLGRAYSYPL
  NSYELKAN
• Function: Regulates autophagy by controlling the spatial distribution and levels of the intracellular phosphatidylinositol 4-phosphate (PtdIns(4)P) pools. Modulates (PtdIns(4)P) levels by regulating the ER-to-Golgi trafficking of the phosphatidylinositide phosphatase SACM1L ; (Microbial infection) Positively regulates the replication of encephalomyocarditis virus (EMCV) via autophagy-dependent pathway.
• Tissue Specificity: Up-regulated in brain tumor glioblastoma multiforme cells (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Primary biliary cholangitis	DIS43E0O	Strong	Genetic Variation	[1]
Systemic lupus erythematosus	DISI1SZ7	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Transmembrane protein 39A (TMEM39A).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Transmembrane protein 39A (TMEM39A).	[4]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Transmembrane protein 39A (TMEM39A).	[5]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 39A (TMEM39A).	[6]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Transmembrane protein 39A (TMEM39A).	[7]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Transmembrane protein 39A (TMEM39A).	[8]
Sulindac	DM2QHZU	Approved	Sulindac increases the expression of Transmembrane protein 39A (TMEM39A).	[9]
Dihydrotestosterone	DM3S8XC	Phase 4	Dihydrotestosterone increases the expression of Transmembrane protein 39A (TMEM39A).	[10]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Transmembrane protein 39A (TMEM39A).	[11]

References

• [1] A genome-wide association study identifies six novel risk loci for primary biliary cholangitis.Nat Commun. 2017 Apr 20;8:14828. doi: 10.1038/ncomms14828.
• [2] Association of novel polymorphisms in TMEM39A gene with systemic lupus erythematosus in a Chinese Han population.BMC Med Genet. 2017 Apr 20;18(1):43. doi: 10.1186/s12881-017-0405-8.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [7] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [8] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [9] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [10] LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. Proc Natl Acad Sci U S A. 2018 May 1;115(18):E4179-E4188.
• [11] Dose- and time-dependent transcriptional response of Ishikawa cells exposed to genistein. Toxicol Sci. 2016 May;151(1):71-87.