Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT76T8O0)

• DOT Name: Protein PET117 homolog, mitochondrial (PET117)
• Gene Name: PET117
• Related Disease:
  Mitochondrial disease
  Posterior polymorphous corneal dystrophy
  Cytochrome-c oxidase deficiency disease
  Leigh syndrome
  Mitochondrial complex 4 deficiency, nuclear type 19
• UniProt ID: PT117_HUMAN
• Pfam ID: PF15786
• Sequence:
  MSRSSKVVLGLSVLLTAATVAGVHVKQQWDQQRLRDGVIRDIERQIRKKENIRLLGEQII
  LTEQLEAEREKMLLAKGSQKS

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[1]
Posterior polymorphous corneal dystrophy	DISHAYH6	Strong	Genetic Variation	[2]
Cytochrome-c oxidase deficiency disease	DISK7N3G	Supportive	Autosomal recessive	[1]
Leigh syndrome	DISWQU45	Limited	Autosomal recessive	[3]
Mitochondrial complex 4 deficiency, nuclear type 19	DISTR4JU	Limited	Unknown	[1]

5 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 Protein PET117 homolog, mitochondrial (PET117).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein PET117 homolog, mitochondrial (PET117).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Protein PET117 homolog, mitochondrial (PET117).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein PET117 homolog, mitochondrial (PET117).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Protein PET117 homolog, mitochondrial (PET117).	[9]

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 Protein PET117 homolog, mitochondrial (PET117).	[8]

References

• [1] Mutated PET117 causes complex IV deficiency and is associated with neurodevelopmental regression and medulla oblongata lesions. Hum Genet. 2017 Jun;136(6):759-769. doi: 10.1007/s00439-017-1794-7. Epub 2017 Apr 6.
• [2] Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression.PLoS One. 2016 Jun 16;11(6):e0157577. doi: 10.1371/journal.pone.0157577. eCollection 2016.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] 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.
• [7] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [8] 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.
• [9] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.