Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTT2FRCJ)

• DOT Name: Cystatin-8 (CST8)
• Synonyms: Cystatin-related epididymal spermatogenic protein
• Gene Name: CST8
• Related Disease:
  Craniosynostosis
  Male infertility
  Melanoma
  Pituitary gland disorder
• UniProt ID: CST8_HUMAN
• Pfam ID: PF00031
• Sequence:
  MPRCRWLSLILLTIPLALVARKDPKKNETGVLRKLKPVNASNANVKQCLWFAMQEYNKES
  EDKYVFLVVKTLQAQLQVTNLLEYLIDVEIARSDCRKPLSTNEICAIQENSKLKRKLSCS
  FLVGALPWNGEFTVMEKKCEDA
• Function: Performs a specialized role during sperm development and maturation.
• Tissue Specificity: Proximal caput region of the epididymis. Lower expression in the testis. Within the testis it is localized to the elongating spermatids, whereas within the epididymis it is exclusively synthesized by the proximal caput epithelium.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Craniosynostosis	DIS6J405	Strong	Biomarker	[1]
Male infertility	DISY3YZZ	Strong	Biomarker	[2]
Melanoma	DIS1RRCY	Strong	Biomarker	[3]
Pituitary gland disorder	DIS7XB48	Strong	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Cystatin-8 (CST8).	[5]
Fluorouracil	DMUM7HZ	Approved	Fluorouracil affects the expression of Cystatin-8 (CST8).	[6]

1 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 increases the methylation of Cystatin-8 (CST8).	[7]

References

• [1] Cytokine release syndrome: grading, modeling, and new therapy.J Hematol Oncol. 2018 Sep 24;11(1):121. doi: 10.1186/s13045-018-0653-x.
• [2] Reduced fertility in vitro in mice lacking the cystatin CRES (cystatin-related epididymal spermatogenic): rescue by exposure of spermatozoa to dibutyryl cAMP and isobutylmethylxanthine.Biol Reprod. 2011 Jan;84(1):140-52. doi: 10.1095/biolreprod.110.084855. Epub 2010 Sep 1.
• [3] Expression analysis of genes identified by molecular profiling of VGP melanomas and MGP melanoma-positive lymph nodes.Cancer Biol Ther. 2004 Jan;3(1):110-20. doi: 10.4161/cbt.3.1.662. Epub 2004 Jan 24.
• [4] CCAAT/enhancer binding protein beta regulates expression of the cystatin-related epididymal spermatogenic (Cres) gene.Biol Reprod. 2001 Nov;65(5):1452-61. doi: 10.1095/biolreprod65.5.1452.
• [5] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [6] Multi-level gene expression profiles affected by thymidylate synthase and 5-fluorouracil in colon cancer. BMC Genomics. 2006 Apr 3;7:68. doi: 10.1186/1471-2164-7-68.
• [7] 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.