Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1GYXDM)

• DOT Name: Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1)
• Gene Name: CYSTM1
• Related Disease: Huntington disease
• UniProt ID: CYTM1_HUMAN
• Sequence:
  MNQENPPPYPGPGPTAPYPPYPPQPMGPGPMGGPYPPPQGYPYQGYPQYGWQGGPQEPPK
  TTVYVVEDQRRDELGPSTCLTACWTALCCCCLWDMLT
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Huntington disease	DISQPLA4	Strong	Biomarker	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[3]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[7]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[8]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[8]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[6]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol decreases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[9]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[10]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[11]
Milchsaure	DM462BT	Investigative	Milchsaure increases the expression of Cysteine-rich and transmembrane domain-containing protein 1 (CYSTM1).	[12]

References

• [1] Huntington's disease biomarker progression profile identified by transcriptome sequencing in peripheral blood.Eur J Hum Genet. 2015 Oct;23(10):1349-56. doi: 10.1038/ejhg.2014.281. Epub 2015 Jan 28.
• [2] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [9] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [10] 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.
• [11] 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.
• [12] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.