Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTNE3T6Z)

• DOT Name: Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2)
• Synonyms: BrX-like translocated in leukemia
• Gene Name: CHIC2
• Related Disease:
  Leukemia
  Lymphosarcoma
  Systemic mastocytosis
  Acute myelogenous leukaemia
• UniProt ID: CHIC2_HUMAN
• Pfam ID: PF10256
• Sequence:
  MADFDEIYEEEEDEERALEEQLLKYSPDPVVVRGSGHVTVFGLSNKFESEFPSSLTGKVA
  PEEFKASINRVNSCLKKNLPVNVRWLLCGCLCCCCTLGCSMWPVICLSKRTRRSIEKLLE
  WENNRLYHKLCLHWRLSKRKCETNNMMEYVILIEFLPKTPIFRPD

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Leukemia	DISNAKFL	Strong	Altered Expression	[1]
Lymphosarcoma	DISGYV3F	Strong	Genetic Variation	[2]
Systemic mastocytosis	DISNQ2OY	moderate	Genetic Variation	[3]
Acute myelogenous leukaemia	DISCSPTN	No Known	Unknown	[4]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Mitomycin	DMH0ZJE	Approved	Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2) affects the response to substance of Mitomycin.	[19]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[5]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the ubiquitination of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[8]

12 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 Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[9]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[11]
Phenobarbital	DMXZOCG	Approved	Phenobarbital affects the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[12]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[13]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[15]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[16]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[17]
chloropicrin	DMSGBQA	Investigative	chloropicrin increases the expression of Cysteine-rich hydrophobic domain-containing protein 2 (CHIC2).	[18]

References

• [1] Fusion of a novel gene, BTL, to ETV6 in acute myeloid leukemias with a t(4;12)(q11-q12;p13).Blood. 1999 Sep 1;94(5):1820-4.
• [2] Characterization of differentially expressed genes in the bovine T lymphoma cell line.Vet Immunol Immunopathol. 1998 Apr 16;62(3):209-19. doi: 10.1016/s0165-2427(98)00098-1.
• [3] CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy.Blood. 2003 Nov 1;102(9):3093-6. doi: 10.1182/blood-2003-05-1627. Epub 2003 Jul 3.
• [4] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [5] 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.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Quantitative Assessment of Arsenite-Induced Perturbation of Ubiquitinated Proteome. Chem Res Toxicol. 2022 Sep 19;35(9):1589-1597. doi: 10.1021/acs.chemrestox.2c00197. Epub 2022 Aug 22.
• [9] Minimal peroxide exposure of neuronal cells induces multifaceted adaptive responses. PLoS One. 2010 Dec 17;5(12):e14352. doi: 10.1371/journal.pone.0014352.
• [10] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [11] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [12] Reproducible chemical-induced changes in gene expression profiles in human hepatoma HepaRG cells under various experimental conditions. Toxicol In Vitro. 2009 Apr;23(3):466-75. doi: 10.1016/j.tiv.2008.12.018. Epub 2008 Dec 30.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [15] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [17] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [18] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.
• [19] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.