Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTESP4WL)

• DOT Name: Clusterin-associated protein 1 (CLUAP1)
• Synonyms: Qilin
• Gene Name: CLUAP1
• Related Disease:
  Cardiovascular disease
  Colon cancer
  Colon carcinoma
  Colonic neoplasm
  Cystic kidney disease
  Joubert syndrome
  Leber congenital amaurosis 9
  Lung neoplasm
  Male infertility
  Osteosarcoma
  Leber congenital amaurosis
• UniProt ID: CLUA1_HUMAN
• Pfam ID: PF10234
• Sequence:
  MSFRDLRNFTEMMRALGYPRHISMENFRTPNFGLVSEVLLWLVKRYEPQTDIPPDVDTEQ
  DRVFFIKAIAQFMATKAHIKLNTKKLYQADGYAVKELLKITSVLYNAMKTKGMEGSEIVE
  EDVNKFKFDLGSKIADLKAARQLASEITSKGASLYDLLGMEVELREMRTEAIARPLEINE
  TEKVMRIAIKEILTQVQKTKDLLNNVASDEANLEAKIEKRKLELERNRKRLETLQSVRPC
  FMDEYEKTEEELQKQYDTYLEKFQNLTYLEQQLEDHHRMEQERFEEAKNTLCLIQNKLKE
  EEKRLLKSGSNDDSDIDIQEDDESDSELEERRLPKPQTAMEMLMQGRPGKRIVGTMQGGD
  SDDNEDSEESEIDMEDDDDEDDDLEDESISLSPTKPNRRVRKSEPLDESDNDF
• Function: Required for cilia biogenesis. Appears to function within the multiple intraflagellar transport complex B (IFT-B). Key regulator of hedgehog signaling.
• Tissue Specificity: Expressed in testis, thyroid and trachea and to a lower extent in spinal cord and adrenal gland. Highly expressed in colon cancer and osteosarcoma cell lines.
• Reactome Pathway: Intraflagellar transport (R-HSA-5620924)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[1]
Colon cancer	DISVC52G	Strong	Altered Expression	[2]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[2]
Colonic neoplasm	DISSZ04P	Strong	Altered Expression	[2]
Cystic kidney disease	DISRT1LM	Strong	Biomarker	[3]
Joubert syndrome	DIS7P5CO	Strong	Genetic Variation	[4]
Leber congenital amaurosis 9	DIS35YGW	Strong	Autosomal recessive	[5]
Lung neoplasm	DISVARNB	Strong	Altered Expression	[6]
Male infertility	DISY3YZZ	Strong	Biomarker	[7]
Osteosarcoma	DISLQ7E2	Strong	Altered Expression	[6]
Leber congenital amaurosis	DISMGH8F	Limited	Autosomal recessive	[5]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Clusterin-associated protein 1 (CLUAP1).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Clusterin-associated protein 1 (CLUAP1).	[9]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Clusterin-associated protein 1 (CLUAP1).	[10]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Clusterin-associated protein 1 (CLUAP1).	[8]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Clusterin-associated protein 1 (CLUAP1).	[12]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Clusterin-associated protein 1 (CLUAP1).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Clusterin-associated protein 1 (CLUAP1).	[15]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Clusterin-associated protein 1 (CLUAP1).	[16]
chloropicrin	DMSGBQA	Investigative	chloropicrin decreases the expression of Clusterin-associated protein 1 (CLUAP1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Clusterin-associated protein 1 (CLUAP1).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Clusterin-associated protein 1 (CLUAP1).	[14]

References

• [1] Leveraging Polygenic Functional Enrichment to Improve GWAS Power.Am J Hum Genet. 2019 Jan 3;104(1):65-75. doi: 10.1016/j.ajhg.2018.11.008. Epub 2018 Dec 27.
• [2] Isolation and characterization of a novel gene CLUAP1 whose expression is frequently upregulated in colon cancer.Oncogene. 2004 Dec 9;23(57):9289-94. doi: 10.1038/sj.onc.1208100.
• [3] Qilin is essential for cilia assembly and normal kidney development in zebrafish.PLoS One. 2011;6(11):e27365. doi: 10.1371/journal.pone.0027365. Epub 2011 Nov 15.
• [4] Compound heterozygous alterations in intraflagellar transport protein CLUAP1 in a child with a novel Joubert and oral-facial-digital overlap syndrome.Cold Spring Harb Mol Case Stud. 2017 Jul 5;3(4):a001321. doi: 10.1101/mcs.a001321. Print 2017 Jul.
• [5] Hypomorphic mutations identified in the candidate Leber congenital amaurosis gene CLUAP1. Genet Med. 2016 Oct;18(10):1044-51. doi: 10.1038/gim.2015.205. Epub 2016 Jan 28.
• [6] Identification of CLUAP1 as a human osteosarcoma tumor-associated antigen recognized by the humoral immune system.Int J Oncol. 2007 Feb;30(2):461-7.
• [7] Qilin pills alleviate oligoasthenospermia by inhibiting Bax-caspase-9 apoptosis pathway in the testes of model rats.Oncotarget. 2018 Apr 24;9(31):21770-21782. doi: 10.18632/oncotarget.24985. eCollection 2018 Apr 24.
• [8] 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.
• [9] 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.
• [10] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [11] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [12] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [13] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [14] 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.
• [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] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [17] Transcriptomic analysis of human primary bronchial epithelial cells after chloropicrin treatment. Chem Res Toxicol. 2015 Oct 19;28(10):1926-35.