Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTLUUDH1)

• DOT Name: Voltage-gated monoatomic cation channel TMEM109 (TMEM109)
• Synonyms: Mitsugumin-23; Mg23; Transmembrane protein 109
• Gene Name: TMEM109
• Related Disease:
  Cardiac failure
  Congestive heart failure
  Myasthenia gravis
• UniProt ID: TM109_HUMAN
• Pfam ID: PF14965
• Sequence:
  MAASSISSPWGKHVFKAILMVLVALILLHSALAQSRRDFAPPGQQKREAPVDVLTQIGRS
  VRGTLDAWIGPETMHLVSESSSQVLWAISSAISVAFFALSGIAAQLLNALGLAGDYLAQG
  LKLSPGQVQTFLLWGAGALVVYWLLSLLLGLVLALLGRILWGLKLVIFLAGFVALMRSVP
  DPSTRALLLLALLILYALLSRLTGSRASGAQLEAKVRGLERQVEELRWRQRRAAKGARSV
  EEE
• Function: Functions as a voltage-gated monoatomic cation channel permeable to both potassium and calcium. Plays a role in the cellular response to DNA damage.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiac failure	DISDC067	Strong	Altered Expression	[1]
Congestive heart failure	DIS32MEA	Strong	Altered Expression	[1]
Myasthenia gravis	DISELRCI	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Voltage-gated monoatomic cation channel TMEM109 (TMEM109).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Voltage-gated monoatomic cation channel TMEM109 (TMEM109).	[4]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Voltage-gated monoatomic cation channel TMEM109 (TMEM109).	[5]
Marinol	DM70IK5	Approved	Marinol decreases the expression of Voltage-gated monoatomic cation channel TMEM109 (TMEM109).	[6]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Voltage-gated monoatomic cation channel TMEM109 (TMEM109).	[7]

References

• [1] Dysregulated Zn(2+) homeostasis impairs cardiac type-2 ryanodine receptor and mitsugumin 23 functions, leading to sarcoplasmic reticulum Ca(2+) leakage.J Biol Chem. 2017 Aug 11;292(32):13361-13373. doi: 10.1074/jbc.M117.781708. Epub 2017 Jun 19.
• [2] Different molecular expression in thymoma with ocular or generalized myasthenia gravis.J Neurol Sci. 2012 Feb 15;313(1-2):27-31. doi: 10.1016/j.jns.2011.09.037. Epub 2011 Oct 13.
• [3] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [4] 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.
• [5] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [6] JunD is involved in the antiproliferative effect of Delta9-tetrahydrocannabinol on human breast cancer cells. Oncogene. 2008 Aug 28;27(37):5033-44.
• [7] 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.