Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTL5PA3Y)

DOT Name	Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2)
Synonyms	Aging-associated gene 10 protein; HCV NS2 trans-regulated protein; NS2TP
Gene Name	CHCHD2
Related Disease	Autoimmune disease ( ) Breast cancer ( ) Breast carcinoma ( ) Charcot-Marie-Tooth disease type 1A ( ) Dementia ( ) Dilated cardiomyopathy 1A ( ) Essential tremor ( ) Frontotemporal dementia ( ) Huntington disease ( ) Invasive ductal breast carcinoma ( ) Lafora disease ( ) Late-onset Parkinson disease ( ) Lewy body dementia ( ) Lissencephaly spectrum disorders ( ) Mitochondrial disease ( ) Motor neurone disease ( ) Non-small-cell lung cancer ( ) Parkinson disease 22, autosomal dominant ( ) Parkinsonian disorder ( ) Pick disease ( ) Zika virus infection ( ) Advanced cancer ( ) Hepatocellular carcinoma ( ) Carcinoma of liver and intrahepatic biliary tract ( ) Clear cell renal carcinoma ( ) Hepatitis C virus infection ( ) Liver cancer ( ) Neoplasm ( ) Renal cell carcinoma ( )
UniProt ID	CHCH2_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
Pfam ID	PF06747
Sequence	MPRGSRSRTSRMAPPASRAPQMRAAPRPAPVAQPPAAAPPSAVGSSAAAPRQPGLMAQMA TTAAGVAVGSAVGHTLGHAITGGFSGGSNAEPARPDITYQEPQGTQPAQQQQPCLYEIKQ FLECAQNQGDIKLCEGFNEVLKQCRLANGLA
Function	Transcription factor. Binds to the oxygen responsive element of COX4I2 and activates its transcription under hypoxia conditions (4% oxygen), as well as normoxia conditions (20% oxygen).
Reactome Pathway	Mitochondrial protein import (R-HSA-1268020 )

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Autoimmune disease	DISORMTM	Strong	Biomarker	[1]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[1]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[1]
Charcot-Marie-Tooth disease type 1A	DISSRZG7	Strong	Genetic Variation	[2]
Dementia	DISXL1WY	Strong	Biomarker	[3]
Dilated cardiomyopathy 1A	DIS0RK9Z	Strong	Biomarker	[1]
Essential tremor	DIS7GBKQ	Strong	Genetic Variation	[4]
Frontotemporal dementia	DISKYHXL	Strong	Genetic Variation	[5]
Huntington disease	DISQPLA4	Strong	Biomarker	[6]
Invasive ductal breast carcinoma	DIS43J58	Strong	Biomarker	[1]
Lafora disease	DIS83JHH	Strong	Genetic Variation	[7]
Late-onset Parkinson disease	DIS9IOUI	Strong	Genetic Variation	[8]
Lewy body dementia	DISAE66J	Strong	Genetic Variation	[7]
Lissencephaly spectrum disorders	DISBCZL7	Strong	Altered Expression	[9]
Mitochondrial disease	DISKAHA3	Strong	Genetic Variation	[5]
Motor neurone disease	DISUHWUI	Strong	Genetic Variation	[10]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Parkinson disease 22, autosomal dominant	DIS6PY08	Strong	Autosomal dominant	[12]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[7]
Pick disease	DISP6X50	Strong	Genetic Variation	[5]
Zika virus infection	DISQUCTY	Strong	Biomarker	[13]
Advanced cancer	DISAT1Z9	moderate	Altered Expression	[14]
Hepatocellular carcinoma	DIS0J828	moderate	Biomarker	[14]
Carcinoma of liver and intrahepatic biliary tract	DIS8WA0W	Limited	Biomarker	[15]
Clear cell renal carcinoma	DISBXRFJ	Limited	Biomarker	[16]
Hepatitis C virus infection	DISQ0M8R	Limited	Biomarker	[15]
Liver cancer	DISDE4BI	Limited	Biomarker	[15]
Neoplasm	DISZKGEW	Limited	Altered Expression	[16]
Renal cell carcinoma	DISQZ2X8	Limited	Biomarker	[16]
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Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[17]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[19]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[20]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[21]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[23]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[24]
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⏷ Show the Full List of 7 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Coiled-coil-helix-coiled-coil-helix domain-containing protein 2 (CHCHD2).	[22]
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References

1	Mitochondrial autoimmunity and MNRR1 in breast carcinogenesis.BMC Cancer. 2019 May 2;19(1):411. doi: 10.1186/s12885-019-5575-7.
2	Abl2 kinase phosphorylates Bi-organellar regulator MNRR1 in mitochondria, stimulating respiration.Biochim Biophys Acta Mol Cell Res. 2017 Feb;1864(2):440-448. doi: 10.1016/j.bbamcr.2016.11.029. Epub 2016 Nov 30.
3	Mutation Screening of the CHCHD2 Gene for Alzheimer's Disease and Frontotemporal Dementia in Chinese Mainland Population.J Alzheimers Dis. 2018;61(4):1283-1288. doi: 10.3233/JAD-170692.
4	Mutation analysis of CHCHD2 gene in Chinese Han familial essential tremor patients and familial Parkinson's disease patients.Neurobiol Aging. 2017 Jan;49:218.e9-218.e11. doi: 10.1016/j.neurobiolaging.2016.10.001. Epub 2016 Oct 11.
5	PD-linked CHCHD2 mutations impair CHCHD10 and MICOS complex leading to mitochondria dysfunction.Hum Mol Genet. 2019 Apr 1;28(7):1100-1116. doi: 10.1093/hmg/ddy413.
6	Early transcriptional changes linked to naturally occurring Huntington's disease mutations in neural derivatives of human embryonic stem cells.Hum Mol Genet. 2012 Sep 1;21(17):3883-95. doi: 10.1093/hmg/dds216. Epub 2012 Jun 7.
7	Mitochondrial targeting sequence variants of the CHCHD2 gene are a risk for Lewy body disorders.Neurology. 2015 Dec 8;85(23):2016-25. doi: 10.1212/WNL.0000000000002170. Epub 2015 Nov 11.
8	Varied pathological and therapeutic response effects associated with CHCHD2 mutant and risk variants.Hum Mutat. 2017 Aug;38(8):978-987. doi: 10.1002/humu.23234. Epub 2017 May 22.
9	CHCHD2 is down-regulated in neuronal cells differentiated from iPS cells derived from patients with lissencephaly.Genomics. 2015 Oct;106(4):196-203. doi: 10.1016/j.ygeno.2015.07.001. Epub 2015 Jul 15.
10	Mitochondrial CHCHD2 and CHCHD10: Roles in Neurological Diseases and Therapeutic Implications.Neuroscientist. 2020 Apr;26(2):170-184. doi: 10.1177/1073858419871214. Epub 2019 Sep 16.
11	CHCHD2 Is Coamplified with EGFR in NSCLC and Regulates Mitochondrial Function and Cell Migration.Mol Cancer Res. 2015 Jul;13(7):1119-29. doi: 10.1158/1541-7786.MCR-14-0165-T. Epub 2015 Mar 17.
12	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.
13	Quantitative Proteomic Analysis of Mosquito C6/36 Cells Reveals Host Proteins Involved in Zika Virus Infection.J Virol. 2017 May 26;91(12):e00554-17. doi: 10.1128/JVI.00554-17. Print 2017 Jun 15.
14	CHCHD2 promotes hepatocellular carcinoma and indicates poor prognosis of hepatocellular carcinoma patients.J Cancer. 2019 Nov 1;10(27):6822-6828. doi: 10.7150/jca.31158. eCollection 2019.
15	Cyclic adenosine monophosphate response element-binding protein transcriptionally regulates CHCHD2 associated with the molecular pathogenesis of hepatocellular carcinoma.Mol Med Rep. 2015 Jun;11(6):4053-62. doi: 10.3892/mmr.2015.3256. Epub 2015 Jan 26.
16	Knockdown of CHCHD2 inhibits migration and angiogenesis of human renal cell carcinoma: A potential molecular marker for treatment of RCC.Oncol Lett. 2019 Jan;17(1):765-772. doi: 10.3892/ol.2018.9686. Epub 2018 Nov 12.
17	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.
18	Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
19	Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
20	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.
21	Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
22	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.
23	Bisphenol A Exposure Changes the Transcriptomic and Proteomic Dynamics of Human Retinoblastoma Y79 Cells. Genes (Basel). 2021 Feb 11;12(2):264. doi: 10.3390/genes12020264.
24	From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.