Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTB0HBP1)

• DOT Name: Spliceosome-associated protein CWC27 homolog (CWC27)
• Synonyms: Antigen NY-CO-10; Probable inactive peptidyl-prolyl cis-trans isomerase CWC27 homolog; PPIase CWC27; Serologically defined colon cancer antigen 10
• Gene Name: CWC27
• Related Disease:
  Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome
  Bladder cancer
  Retinitis pigmentosa
  Urinary bladder cancer
  Urinary bladder neoplasm
• UniProt ID: CWC27_HUMAN
• PDB ID: 2HQ6; 4R3E; 5Z56; 5Z58; 6FF4; 6FF7; 6YVH; 7DVQ
• Pfam ID: PF00160
• Sequence:
  MSNIYIQEPPTNGKVLLKTTAGDIDIELWSKEAPKACRNFIQLCLEAYYDNTIFHRVVPG
  FIVQGGDPTGTGSGGESIYGAPFKDEFHSRLRFNRRGLVAMANAGSHDNGSQFFFTLGRA
  DELNNKHTIFGKVTGDTVYNMLRLSEVDIDDDERPHNPHKIKSCEVLFNPFDDIIPREIK
  RLKKEKPEEEVKKLKPKGTKNFSLLSFGEEAEEEEEEVNRVSQSMKGKSKSSHDLLKDDP
  HLSSVPVVESEKGDAPDLVDDGEDESAEHDEYIDGDEKNLMRERIAKKLKKDTSANVKSA
  GEGEVEKKSVSRSEELRKEARQLKRELLAAKQKKVENAAKQAEKRSEEEEAPPDGAVAEY
  RREKQKYEALRKQQSKKGTSREDQTLALLNQFKSKLTQAIAETPENDIPETEVEDDEGWM
  SHVLQFEDKSRKVKDASMQDSDTFEIYDPRNPVNKRRREESKKLMREKKERR
• Function: As part of the spliceosome, plays a role in pre-mRNA splicing. Probable inactive PPIase with no peptidyl-prolyl cis-trans isomerase activity. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs (Probable).
• Reactome Pathway: mRNA Splicing - Major Pathway (R-HSA-72163)

Molecular Interaction Atlas (MIA) of This DOT

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Metaphyseal chondrodysplasia-retinitis pigmentosa syndrome	DISGGEUO	Definitive	Autosomal recessive	[1]
Bladder cancer	DISUHNM0	Strong	Genetic Variation	[2]
Retinitis pigmentosa	DISCGPY8	Strong	Biomarker	[1]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[2]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Daunorubicin	DMQUSBT	Approved	Spliceosome-associated protein CWC27 homolog (CWC27) affects the response to substance of Daunorubicin.	[13]

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 Spliceosome-associated protein CWC27 homolog (CWC27).	[3]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[4]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[6]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[7]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[8]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[10]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[11]
[3H]methyltrienolone	DMTSGOW	Investigative	[3H]methyltrienolone increases the expression of Spliceosome-associated protein CWC27 homolog (CWC27).	[12]

References

• [1] Mutations in the Spliceosome Component CWC27 Cause Retinal Degeneration with or without Additional Developmental Anomalies. Am J Hum Genet. 2017 Apr 6;100(4):592-604. doi: 10.1016/j.ajhg.2017.02.008. Epub 2017 Mar 9.
• [2] Genome-Wide Association Study of Bladder Cancer in a Chinese Cohort Reveals a New Susceptibility Locus at 5q12.3.Cancer Res. 2016 Jun 1;76(11):3277-84. doi: 10.1158/0008-5472.CAN-15-2564. Epub 2016 Mar 29.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] 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.
• [5] 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.
• [6] The thioxotriazole copper(II) complex A0 induces endoplasmic reticulum stress and paraptotic death in human cancer cells. J Biol Chem. 2009 Sep 4;284(36):24306-19.
• [7] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [8] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [9] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [10] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [12] Analysis of the prostate cancer cell line LNCaP transcriptome using a sequencing-by-synthesis approach. BMC Genomics. 2006 Sep 29;7:246. doi: 10.1186/1471-2164-7-246.
• [13] Mapping genes that contribute to daunorubicin-induced cytotoxicity. Cancer Res. 2007 Jun 1;67(11):5425-33. doi: 10.1158/0008-5472.CAN-06-4431.