Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9O7UZE)

• DOT Name: Complex III assembly factor LYRM7 (LYRM7)
• Synonyms: LYR motif-containing protein 7
• Gene Name: LYRM7
• Related Disease:
  Mitochondrial disease
  Mitochondrial complex III deficiency nuclear type 8
  Mitochondrial complex III deficiency
• UniProt ID: LYRM7_HUMAN
• Pfam ID: PF05347
• Sequence:
  MGRAVKVLQLFKTLHRTRQQVFKNDARALEAARIKINEEFKNNKSETSSKKIEELMKIGS
  DVELLLRTSVIQGIHTDHNTLKLVPRKDLLVENVPYCDAPTQKQ
• Function: Assembly factor required for Rieske Fe-S protein UQCRFS1 incorporation into the cytochrome b-c1 (CIII) complex. Functions as a chaperone, binding to this subunit within the mitochondrial matrix and stabilizing it prior to its translocation and insertion into the late CIII dimeric intermediate within the mitochondrial inner membrane.

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]
Mitochondrial complex III deficiency nuclear type 8	DIST3PXS	Strong	Autosomal recessive	[2]
Mitochondrial complex III deficiency	DISSUPJ6	Supportive	Autosomal recessive	[2]

6 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 Complex III assembly factor LYRM7 (LYRM7).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Complex III assembly factor LYRM7 (LYRM7).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Complex III assembly factor LYRM7 (LYRM7).	[5]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Complex III assembly factor LYRM7 (LYRM7).	[6]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Complex III assembly factor LYRM7 (LYRM7).	[7]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Complex III assembly factor LYRM7 (LYRM7).	[8]

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] A homozygous mutation in LYRM7/MZM1L associated with early onset encephalopathy, lactic acidosis, and severe reduction of mitochondrial complex III activity. Hum Mutat. 2013 Dec;34(12):1619-22. doi: 10.1002/humu.22441. Epub 2013 Sep 23.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [6] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [7] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [8] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.