Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB5ZUYF)

• DOT Name: Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD)
• Gene Name: MTHFSD
• Related Disease:
  Amyotrophic lateral sclerosis
  Huntington disease
• UniProt ID: MTHSD_HUMAN
• PDB ID: 2E5J
• Pfam ID: PF01812 ; PF00076
• Sequence:
  MEPRAVGVSKQDIREQIWGYMESQNLADFPRPVHHRIPNFKGSYLACQNIKDLDVFARTQ
  EVKVDPDKPLEGVRLLVLQSKKTLLVPTPRLRTGLFNKITPPPGATKDILRKCATSQGVR
  NYSVPIGLDSRVLVDLVVVGSVAVSEKGWRIGKGEGYADLEYAMMVSMGAVSKETPVVTI
  VHDCQVVDIPEELVEEHDITVDYILTPTRVIATGCKRPKPMGITWFKISLEMMEKIPILR
  SLRAREQQAGKDVTLQGEHQHLPEPGCQQTVPLSVGRRPPDTPGPETNSMEAAPGSPPGE
  GAPLAADVYVGNLPGDARVSDLKRALRELGSVPLRLTWQGPRRRAFLHYPDSAAAQQAVS
  CLQGLRLGTDTLRVALARQQRDK

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Genetic Variation	[1]
Huntington disease	DISQPLA4	Limited	Genetic Variation	[1]

6 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 Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[2]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[4]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[2]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[7]

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 affects the methylation of Methenyltetrahydrofolate synthase domain-containing protein (MTHFSD).	[5]

References

• [1] Rare homozygosity in amyotrophic lateral sclerosis suggests the contribution of recessive variants to disease genetics.J Neurol Sci. 2019 Jul 15;402:62-68. doi: 10.1016/j.jns.2019.05.006. Epub 2019 May 8.
• [2] 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.
• [3] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.