Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQ0J3DT)

• DOT Name: Protein PET100 homolog, mitochondrial (PET100)
• Gene Name: PET100
• Related Disease:
  Cytochrome-c oxidase deficiency disease
  Mitochondrial complex 4 deficiency, nuclear type 12
  Intellectual disability
  Leigh syndrome
  Obsolete Leigh syndrome with leukodystrophy
• UniProt ID: PT100_HUMAN
• Pfam ID: PF09803
• Sequence:
  MGVKLEIFRMIIYLTFPVAMFWVSNQAEWFEDDVIQRKRELWPPEKLQEIEEFKERLRKR
  REEKLLRDAQQNS
• Function: Plays an essential role in mitochondrial complex IV maturation and assembly.

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cytochrome-c oxidase deficiency disease	DISK7N3G	Strong	Autosomal recessive	[1]
Mitochondrial complex 4 deficiency, nuclear type 12	DISUR31D	Strong	Autosomal recessive	[2]
Intellectual disability	DISMBNXP	moderate	Biomarker	[3]
Leigh syndrome	DISWQU45	Moderate	Autosomal recessive	[4]
Obsolete Leigh syndrome with leukodystrophy	DISABU9D	Supportive	Autosomal recessive	[5]

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 Protein PET100 homolog, mitochondrial (PET100).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Protein PET100 homolog, mitochondrial (PET100).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein PET100 homolog, mitochondrial (PET100).	[8]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Protein PET100 homolog, mitochondrial (PET100).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Protein PET100 homolog, mitochondrial (PET100).	[10]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Protein PET100 homolog, mitochondrial (PET100).	[11]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [3] A truncating PET100 variant causing fatal infantile lactic acidosis and isolated cytochrome c oxidase deficiency.Eur J Hum Genet. 2015 Jul;23(7):935-9. doi: 10.1038/ejhg.2014.214. Epub 2014 Oct 8.
• [4] 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.
• [5] A founder mutation in PET100 causes isolated complex IV deficiency in Lebanese individuals with Leigh syndrome. Am J Hum Genet. 2014 Feb 6;94(2):209-22. doi: 10.1016/j.ajhg.2013.12.015. Epub 2014 Jan 23.
• [6] 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.
• [7] 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.
• [8] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [9] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [10] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [11] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.