Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8JJ5TP)

• DOT Name: Complex I assembly factor TMEM126B, mitochondrial (TMEM126B)
• Synonyms: Transmembrane protein 126B
• Gene Name: TMEM126B
• Related Disease:
  Mitochondrial disease
  Cardiomyopathy
  Chronic kidney disease
  Metabolic disorder
  Mitochondrial complex 1 deficiency, nuclear type 29
  Myopathy
  Mitochondrial complex I deficiency
• UniProt ID: T126B_HUMAN
• Pfam ID: PF07114
• Sequence:
  MVVFGYEAGTKPRDSGVVPVGTEEAPKVFKMAASMHGQPSPSLEDAKLRRPMVIEIIEKN
  FDYLRKEMTQNIYQMATFGTTAGFSGIFSNFLFRRCFKVKHDALKTYASLATLPFLSTVV
  TDKLFVIDALYSDNISKENCVFRSSLIGIVCGVFYPSSLAFTKNGRLATKYHTVPLPPKG
  RVLIHWMTLCQTQMKLMAIPLVFQIMFGILNGLYHYAVFEETLEKTIHEE
• Function: As part of the MCIA complex, involved in the assembly of the mitochondrial complex I. Participates in constructing the membrane arm of complex I.
• Reactome Pathway: Complex I biogenesis (R-HSA-6799198)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[1]
Cardiomyopathy	DISUPZRG	Strong	Genetic Variation	[2]
Chronic kidney disease	DISW82R7	Strong	Biomarker	[3]
Metabolic disorder	DIS71G5H	Strong	Biomarker	[3]
Mitochondrial complex 1 deficiency, nuclear type 29	DIS8S5LP	Strong	Autosomal recessive	[4]
Myopathy	DISOWG27	Strong	Genetic Variation	[2]
Mitochondrial complex I deficiency	DIS13M7V	Supportive	Autosomal recessive	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Complex I assembly factor TMEM126B, mitochondrial (TMEM126B).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Complex I assembly factor TMEM126B, mitochondrial (TMEM126B).	[6]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Complex I assembly factor TMEM126B, mitochondrial (TMEM126B).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Complex I assembly factor TMEM126B, mitochondrial (TMEM126B).	[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 Complex I assembly factor TMEM126B, mitochondrial (TMEM126B).	[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] Biallelic Mutations in TMEM126B Cause Severe Complex I Deficiency with a Variable Clinical Phenotype.Am J Hum Genet. 2016 Jul 7;99(1):217-27. doi: 10.1016/j.ajhg.2016.05.021. Epub 2016 Jun 30.
• [3] Transmembrane protein 126B protects against high fat diet (HFD)-induced renal injury by suppressing dyslipidemia via inhibitionof ROS.Biochem Biophys Res Commun. 2019 Jan 29;509(1):40-47. doi: 10.1016/j.bbrc.2018.12.003. Epub 2018 Dec 20.
• [4] Mutations in Complex I Assembly Factor TMEM126B Result in Muscle Weakness and Isolated Complex I Deficiency. Am J Hum Genet. 2016 Jul 7;99(1):208-16. doi: 10.1016/j.ajhg.2016.05.022. Epub 2016 Jun 30.
• [5] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [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] 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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.