Details of Drug Off-Target (DOT)

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

• DOT Name: Major facilitator superfamily domain-containing protein 1 (MFSD1)
• Synonyms: Smooth muscle cell-associated protein 4; SMAP-4
• Gene Name: MFSD1
• Related Disease:
  Periodontitis
  High blood pressure
  Type-1/2 diabetes
• UniProt ID: MFSD1_HUMAN
• Pfam ID: PF07690
• Sequence:
  MEEEDEEARALLAGGPDEADRGAPAAPGALPALCDPSRLAHRLLVLLLMCFLGFGSYFCY
  DNPAALQTQVKRDMQVNTTKFMLLYAWYSWPNVVLCFFGGFLIDRVFGIRWGTIIFSCFV
  CIGQVVFALGGIFNAFWLMEFGRFVFGIGGESLAVAQNTYAVSWFKGKELNLVFGLQLSM
  ARIGSTVNMNLMGWLYSKIEALLGSAGHTTLGITLMIGGITCILSLICALALAYLDQRAE
  RILHKEQGKTGEVIKLTDVKDFSLPLWLIFIICVCYYVAVFPFIGLGKVFFTEKFGFSSQ
  AASAINSVVYVISAPMSPVFGLLVDKTGKNIIWVLCAVAATLVSHMMLAFTMWNPWIAMC
  LLGLSYSLLACALWPMVAFVVPEHQLGTAYGFMQSIQNLGLAIISIIAGMILDSRGYLFL
  EVFFIACVSLSLLSVVLLYLVNRAQGGNLNYSARQREEIKFSHTE
• Function: Lysosomal transporter which is essential for liver homeostasis. Required to maintain stability and lysosomal localization of GLMP.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Periodontitis	DISI9JOI	Strong	Biomarker	[1]
High blood pressure	DISY2OHH	Limited	Biomarker	[1]
Type-1/2 diabetes	DISIUHAP	Limited	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[6]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[7]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[8]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Major facilitator superfamily domain-containing protein 1 (MFSD1).	[10]

References

• [1] Screening of Genetic Factor in the Interaction Between Periodontitis and Metabolic Traits Using Candidate Gene Association Study (CGAS).Biochem Genet. 2019 Jun;57(3):466-474. doi: 10.1007/s10528-018-9899-9. Epub 2018 Dec 13.
• [2] Comparative gene expression profile and DNA methylation status in diabetic patients of Kazak and Han people.Medicine (Baltimore). 2018 Sep;97(36):e11982. doi: 10.1097/MD.0000000000011982.
• [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] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] 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.
• [7] 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.
• [8] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [9] 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.
• [10] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.