Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNNPM61)

• DOT Name: MICOS complex subunit MIC13 (MICOS13)
• Synonyms: Protein P117
• Gene Name: MICOS13
• Related Disease:
  Mitochondrial disease
  3-methylglutaconic aciduria
  3-methylglutaconic aciduria type 3
• UniProt ID: MIC13_HUMAN
• Pfam ID: PF15884
• Sequence:
  MVARVWSLMRFLIKGSVAGGAVYLVYDQELLGPSDKSQAALQKAGEVVPPAMYQFSQYVC
  QQTGLQIPQLPAPPKIYFPIRDSWNAGIMTVMSALSVAPSKAREYSKEGWEYVKARTK
• Function: Component of the MICOS complex, a large protein complex of the mitochondrial inner membrane that plays crucial roles in the maintenance of crista junctions, inner membrane architecture, and formation of contact sites to the outer membrane. Constituent of mature MICOS complex, it is required for the formation of cristae junction (CJ) and maintenance of cristae morphology. Required for the incorporation of MICOS10/MIC10 into the MICOS complex.
• Reactome Pathway: Cristae formation (R-HSA-8949613)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[1]
3-methylglutaconic aciduria	DIS8G1WP	moderate	Genetic Variation	[2]
3-methylglutaconic aciduria type 3	DISDQMDY	Supportive	Autosomal recessive	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of MICOS complex subunit MIC13 (MICOS13).	[3]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of MICOS complex subunit MIC13 (MICOS13).	[4]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of MICOS complex subunit MIC13 (MICOS13).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of MICOS complex subunit MIC13 (MICOS13).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of MICOS complex subunit MIC13 (MICOS13).	[7]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of MICOS complex subunit MIC13 (MICOS13).	[8]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of MICOS complex subunit MIC13 (MICOS13).	[9]

References

• [1] 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.
• [2] Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a MICOS complex subunit. Eur J Hum Genet. 2016 Dec;24(12):1778-1782. doi: 10.1038/ejhg.2016.83. Epub 2016 Aug 3.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Low doses of cisplatin induce gene alterations, cell cycle arrest, and apoptosis in human promyelocytic leukemia cells. Biomark Insights. 2016 Aug 24;11:113-21.
• [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] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] 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.
• [8] 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.
• [9] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.