Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTVSJ1AR)

• DOT Name: Protein C19orf12 (C19ORF12)
• Gene Name: C19ORF12
• Related Disease:
  Dementia
  Neurodegeneration with brain iron accumulation 4
  Amyotrophic lateral sclerosis
  DiGeorge syndrome
  Dystonia
  Hereditary spastic paraplegia
  Juvenile amyotrophic lateral sclerosis
  Late-onset Parkinson disease
  Leigh syndrome
  Motor neurone disease
  Neurodegeneration with brain iron accumulation 2A
  Ovarian cancer
  Ovarian neoplasm
  Parkinson disease
  Parkinsonian disorder
  Parkinsonian-pyramidal syndrome
  Woodhouse-Sakati syndrome
  Behr syndrome
  Hereditary spastic paraplegia 43
  Pantothenate kinase-associated neurodegeneration
• UniProt ID: CS012_HUMAN
• Pfam ID: PF20721
• Sequence:
  MERLKSHKPATMTIMVEDIMKLLCSLSGERKMKAAVKHSGKGALVTGAMAFVGGLVGGPP
  GLAVGGAVGGLLGAWMTSGQFKPVPQILMELPPAEQQRLFNEAAAIIRHLEWTDAVQLTA
  LVMGSEALQQQLLAMLVNYVTKELRAEIQYDD

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Dementia	DISXL1WY	Definitive	Biomarker	[1]
Neurodegeneration with brain iron accumulation 4	DIS4BRAY	Definitive	Autosomal recessive	[2]
Amyotrophic lateral sclerosis	DISF7HVM	Strong	Biomarker	[3]
DiGeorge syndrome	DIST1RKO	Strong	Biomarker	[4]
Dystonia	DISJLFGW	Strong	Genetic Variation	[5]
Hereditary spastic paraplegia	DISGZQV1	Strong	Biomarker	[1]
Juvenile amyotrophic lateral sclerosis	DISKDZC9	Strong	Genetic Variation	[6]
Late-onset Parkinson disease	DIS9IOUI	Strong	Biomarker	[7]
Leigh syndrome	DISWQU45	Strong	Genetic Variation	[5]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[6]
Neurodegeneration with brain iron accumulation 2A	DIS9XEBF	Strong	Genetic Variation	[8]
Ovarian cancer	DISZJHAP	Strong	Biomarker	[9]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[9]
Parkinson disease	DISQVHKL	Strong	Biomarker	[7]
Parkinsonian disorder	DISHGY45	Strong	Genetic Variation	[7]
Parkinsonian-pyramidal syndrome	DISHIIPA	Strong	Genetic Variation	[10]
Woodhouse-Sakati syndrome	DISHLVWB	Strong	Genetic Variation	[11]
Behr syndrome	DIS0X9PZ	Limited	Genetic Variation	[12]
Hereditary spastic paraplegia 43	DISJGOU9	Limited	Autosomal recessive	[13]
Pantothenate kinase-associated neurodegeneration	DIS50V55	Limited	Biomarker	[14]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Protein C19orf12 (C19ORF12).	[15]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein C19orf12 (C19ORF12).	[16]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Protein C19orf12 (C19ORF12).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein C19orf12 (C19ORF12).	[18]
Dexamethasone	DMMWZET	Approved	Dexamethasone increases the expression of Protein C19orf12 (C19ORF12).	[20]
Fenofibrate	DMFKXDY	Approved	Fenofibrate increases the expression of Protein C19orf12 (C19ORF12).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Protein C19orf12 (C19ORF12).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein C19orf12 (C19ORF12).	[23]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Protein C19orf12 (C19ORF12).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Protein C19orf12 (C19ORF12).	[25]

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 Protein C19orf12 (C19ORF12).	[19]

References

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• [2] 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.
• [3] Mutation screening of SLC52A3, C19orf12, and TARDBP in Iranian ALS patients.Neurobiol Aging. 2019 Mar;75:225.e9-225.e14. doi: 10.1016/j.neurobiolaging.2018.11.003. Epub 2018 Nov 16.
• [4] Neuropathology of genetic synucleinopathies with parkinsonism: Review of the literature.Mov Disord. 2017 Nov;32(11):1504-1523. doi: 10.1002/mds.27193.
• [5] Movement disorders in mitochondrial diseases.Rev Neurol (Paris). 2016 Aug-Sep;172(8-9):524-529. doi: 10.1016/j.neurol.2016.07.003. Epub 2016 Jul 28.
• [6] C19orf12 mutations in neurodegeneration with brain iron accumulation mimicking juvenile amyotrophic lateral sclerosis.J Neurol. 2012 Nov;259(11):2434-9. doi: 10.1007/s00415-012-6521-7. Epub 2012 May 15.
• [7] Mutations in C19orf12 and intronic repeat expansions in C9orf72 not observed in Iranian Parkinson's disease patients.Neurobiol Aging. 2017 Jun;54:214.e11-214.e12. doi: 10.1016/j.neurobiolaging.2017.03.020. Epub 2017 Mar 18.
• [8] Excess iron harms the brain: the syndromes of neurodegeneration with brain iron accumulation (NBIA).J Neural Transm (Vienna). 2013 Apr;120(4):695-703. doi: 10.1007/s00702-012-0922-8. Epub 2012 Dec 2.
• [9] URI is an oncogene amplified in ovarian cancer cells and is required for their survival. Cancer Cell. 2011 Mar 8;19(3):317-32. doi: 10.1016/j.ccr.2011.01.019.
• [10] C19orf12 mutation leads to a pallido-pyramidal syndrome. Gene. 2014 Mar 10;537(2):352-6. doi: 10.1016/j.gene.2013.11.039. Epub 2013 Dec 17.
• [11] A diagnostic approach for neurodegeneration with brain iron accumulation: clinical features, genetics and brain imaging.Arq Neuropsiquiatr. 2016 Jul;74(7):587-96. doi: 10.1590/0004-282X20160080.
• [12] Behr syndrome with homozygous C19ORF12 mutation.J Neurol Sci. 2015 Oct 15;357(1-2):115-8. doi: 10.1016/j.jns.2015.07.009. Epub 2015 Jul 9.
• [13] 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.
• [14] "Eye of tiger sign" mimic in an adolescent boy with mitochondrial membrane protein associated neurodegeneration (MPAN).Brain Dev. 2016 May;38(5):516-9. doi: 10.1016/j.braindev.2015.10.017. Epub 2015 Nov 18.
• [15] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [16] 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.
• [17] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [18] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [19] 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.
• [20] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [21] Transcriptomic analysis of untreated and drug-treated differentiated HepaRG cells over a 2-week period. Toxicol In Vitro. 2015 Dec 25;30(1 Pt A):27-35.
• [22] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [23] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [24] 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.
• [25] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.