Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTP0OY77)

• DOT Name: Mitochondrial coenzyme A transporter SLC25A42 (SLC25A42)
• Synonyms: Solute carrier family 25 member 42
• Gene Name: SLC25A42
• Related Disease: Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression
• UniProt ID: S2542_HUMAN
• Pfam ID: PF00153
• Sequence:
  MGNGVKEGPVRLHEDAEAVLSSSVSSKRDHRQVLSSLLSGALAGALAKTAVAPLDRTKII
  FQVSSKRFSAKEAFRVLYYTYLNEGFLSLWRGNSATMVRVVPYAAIQFSAHEEYKRILGS
  YYGFRGEALPPWPRLFAGALAGTTAASLTYPLDLVRARMAVTPKEMYSNIFHVFIRISRE
  EGLKTLYHGFMPTVLGVIPYAGLSFFTYETLKSLHREYSGRRQPYPFERMIFGACAGLIG
  QSASYPLDVVRRRMQTAGVTGYPRASIARTLRTIVREEGAVRGLYKGLSMNWVKGPIAVG
  ISFTTFDLMQILLRHLQS
• Function: Mitochondrial carrier mediating the transport of coenzyme A (CoA) in mitochondria in exchange for intramitochondrial (deoxy)adenine nucleotides and adenosine 3',5'-diphosphate.
• Reactome Pathway: Vitamin B5 (pantothenate) metabolism (R-HSA-199220)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metabolic crises, recurrent, with variable encephalomyopathic features and neurologic regression	DISYBJBJ	Strong	Autosomal recessive	[1]

5 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 Mitochondrial coenzyme A transporter SLC25A42 (SLC25A42).	[2]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Mitochondrial coenzyme A transporter SLC25A42 (SLC25A42).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Mitochondrial coenzyme A transporter SLC25A42 (SLC25A42).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Mitochondrial coenzyme A transporter SLC25A42 (SLC25A42).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Mitochondrial coenzyme A transporter SLC25A42 (SLC25A42).	[6]

References

• [1] Mutation of the mitochondrial carrier SLC25A42 causes a novel form of mitochondrial myopathy in humans. Hum Genet. 2016 Jan;135(1):21-30. doi: 10.1007/s00439-015-1608-8. Epub 2015 Nov 5.
• [2] 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.
• [3] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [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] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [6] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.