Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUXN7CO)

• DOT Name: Cystin-1 (CYS1)
• Synonyms: Cilia-associated protein
• Gene Name: CYS1
• Related Disease:
  Autosomal recessive polycystic kidney disease
  Chronic bronchitis
  Chronic obstructive pulmonary disease
  Cystic kidney disease
  Nephronophthisis
  Senior-Boichis syndrome
  Polycystic kidney disease
• UniProt ID: CYS1_HUMAN
• Sequence:
  MGSGSSRSSRTLRRRRSPESLPAGPGAAALEGGTRRRVPVAAAEVPGAAAEEAPGRDPSP
  VAPPDGRDETLRLLDELLAESAAWGPPEPAPRRPARLRPTAVAGSAVCAEQSTEGHPGSG
  NVSEAPGSGRKKPERPAAISYDHSEEGLMASIEREYCR
• Tissue Specificity: Expressed at high levels in the kidney and pancreas. Moderate expression seen in the skeletal muscle, liver and heart. A weak expression seen in the brain, lung, uterus, prostate, testis, small intestine and colon.
• Reactome Pathway: Trafficking of myristoylated proteins to the cilium (R-HSA-5624138)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autosomal recessive polycystic kidney disease	DISPUS40	Strong	Biomarker	[1]
Chronic bronchitis	DISS8O8V	Strong	Genetic Variation	[2]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[2]
Cystic kidney disease	DISRT1LM	Strong	Biomarker	[3]
Nephronophthisis	DISXU4HY	Strong	Genetic Variation	[4]
Senior-Boichis syndrome	DISQ4EJN	Strong	Genetic Variation	[5]
Polycystic kidney disease	DISWS3UY	Moderate	Autosomal recessive	[6]

3 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 Cystin-1 (CYS1).	[7]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Cystin-1 (CYS1).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cystin-1 (CYS1).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cystin-1 (CYS1).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Cystin-1 (CYS1).	[10]

References

• [1] Cystin localizes to primary cilia via membrane microdomains and a targeting motif.J Am Soc Nephrol. 2009 Dec;20(12):2570-80. doi: 10.1681/ASN.2009020188. Epub 2009 Oct 22.
• [2] Genetic susceptibility for chronic bronchitis in chronic obstructive pulmonary disease.Respir Res. 2014 Sep 21;15(1):113. doi: 10.1186/s12931-014-0113-2.
• [3] Systems biology of autosomal dominant polycystic kidney disease (ADPKD): computational identification of gene expression pathways and integrated regulatory networks.Hum Mol Genet. 2009 Jul 1;18(13):2328-43. doi: 10.1093/hmg/ddp165. Epub 2009 Apr 3.
• [4] Mutational analysis in 119 families with nephronophthisis.Pediatr Nephrol. 2007 Mar;22(3):366-70. doi: 10.1007/s00467-006-0334-9. Epub 2006 Oct 24.
• [5] Identification of the human CYS1 gene and candidate gene analysis in Boichis disease.Pediatr Nephrol. 2003 Jun;18(6):498-505. doi: 10.1007/s00467-003-1141-1. Epub 2003 May 6.
• [6] 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.
• [7] Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
• [8] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [9] 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.
• [10] 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.
• [11] 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.