Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9SPG2X)

• DOT Name: Putative transferase CAF17, mitochondrial (IBA57)
• Synonyms: EC 2.1.-.-; Iron-sulfur cluster assembly factor homolog
• Gene Name: IBA57
• Related Disease:
  Mitochondrial disease
  Multiple mitochondrial dysfunctions syndrome 4
  Hereditary spastic paraplegia
  Leukodystrophy
  Multiple mitochondrial dysfunctions syndrome 3
  Myopathy
  Hereditary spastic paraplegia 74
  Lactic acidosis
• UniProt ID: CAF17_HUMAN
• PDB ID: 6GEU; 6QE3; 6QE4
• EC Number: 2.1.-.-
• Sequence:
  MATAALLRGATPGRGGPVWRWRLRAAPRCRLAHSSCSPGGDPTAGAAWACFRLDGRTLLR
  VRGPDAAPFLLGLLTNELPLPSPAAAGAPPAARAGYAHFLNVQGRTLYDVILYGLQEHSE
  VSGFLLECDSSVQGALQKHLALYRIRRKVTVEPHPELRVWAVLPSSPEACGAASLQERAG
  AAAILIRDPRTARMGWRLLTQDEGPALVPGGRLGDLWDYHQHRYLQGVPEGVRDLPPGVA
  LPLESNLAFMNGVSFTKGCYIGQELTARTHHMGVIRKRLFPVRFLDPLPTSGITPGATVL
  TASGQTVGKFRAGQGNVGLALLWSEKIKGPLHIRASEGAQVALAASVPDWWPTVSK
• Function: Involved in the maturation of mitochondrial 4Fe-4S proteins functioning late in the iron-sulfur cluster assembly pathway.
• Tissue Specificity: Expressed in skin fibroblasts and skeletal muscle (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Mitochondrial disease	DISKAHA3	Definitive	Autosomal recessive	[1]
Multiple mitochondrial dysfunctions syndrome 4	DIS42DWP	Definitive	Biomarker	[2]
Hereditary spastic paraplegia	DISGZQV1	Strong	Genetic Variation	[3]
Leukodystrophy	DISVY1TT	Strong	Genetic Variation	[4]
Multiple mitochondrial dysfunctions syndrome 3	DISTIUPO	Strong	Autosomal recessive	[5]
Myopathy	DISOWG27	Strong	Genetic Variation	[6]
Hereditary spastic paraplegia 74	DIS2QRMP	Supportive	Autosomal recessive	[3]
Lactic acidosis	DISZI1ZK	Limited	Biomarker	[7]

4 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Putative transferase CAF17, mitochondrial (IBA57).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Putative transferase CAF17, mitochondrial (IBA57).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Putative transferase CAF17, mitochondrial (IBA57).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Putative transferase CAF17, mitochondrial (IBA57).	[11]

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] ISCA1 mutation in a patient with infantile-onset leukodystrophy causes defects in mitochondrial [4Fe-4S] proteins.Hum Mol Genet. 2018 Aug 1;27(15):2739-2754. doi: 10.1093/hmg/ddy183.
• [3] Fe/S protein assembly gene IBA57 mutation causes hereditary spastic paraplegia. Neurology. 2015 Feb 17;84(7):659-67. doi: 10.1212/WNL.0000000000001270. Epub 2015 Jan 21.
• [4] Expanding the phenotype of IBA57 mutations: related leukodystrophy can remain asymptomatic.J Hum Genet. 2018 Dec;63(12):1223-1229. doi: 10.1038/s10038-018-0516-x. Epub 2018 Sep 27.
• [5] The Gene Curation Coalition: A global effort to harmonize gene-disease evidence resources. Genet Med. 2022 Aug;24(8):1732-1742. doi: 10.1016/j.gim.2022.04.017. Epub 2022 May 4.
• [6] Mutation of the iron-sulfur cluster assembly gene IBA57 causes severe myopathy and encephalopathy. Hum Mol Genet. 2013 Jul 1;22(13):2590-602. doi: 10.1093/hmg/ddt107. Epub 2013 Mar 5.
• [7] Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes.J Neurol. 2017 Jan;264(1):102-111. doi: 10.1007/s00415-016-8312-z. Epub 2016 Oct 26.
• [8] 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.
• [9] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [10] 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.
• [11] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.