Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7H1YOY)

• DOT Name: Cysteine-rich protein 3 (CRIP3)
• Synonyms: CRP-3; Chromosome 6 LIM domain only protein; h6LIMo
• Gene Name: CRIP3
• Related Disease:
  Rheumatoid arthritis
  Early-onset anterior polar cataract
  Gout
  High blood pressure
  Neoplasm
  Stroke
  Squamous cell carcinoma
  Venous thromboembolism
• UniProt ID: CRIP3_HUMAN
• Pfam ID: PF00412
• Sequence:
  MSWTCPRCQQPVFFAEKVSSLGKNWHRFCLKCERCHSILSPGGHAEHNGRPYCHKPCYGA
  LFGPRGVNIGGVGSYLYNPPTPSPGCTTPLSPSSFSPPRPRTGLPQGKKSPPHMKTFTGE
  TSLCPGCGEPVYFAEKVMSLGRNWHRPCLRCQRCHKTLTAGSHAEHDGVPYCHVPCYGYL
  FGPKGGQPHPRHWDGMYMPEVWHVHGLWVCVDNFPCG
• Tissue Specificity: Expressed in most tissues, but not in skeletal muscle.

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Rheumatoid arthritis	DISTSB4J	Definitive	Biomarker	[1]
Early-onset anterior polar cataract	DISTOPIY	Strong	Altered Expression	[2]
Gout	DISHC0U7	Strong	Genetic Variation	[3]
High blood pressure	DISY2OHH	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Stroke	DISX6UHX	moderate	Genetic Variation	[6]
Squamous cell carcinoma	DISQVIFL	Limited	Posttranslational Modification	[7]
Venous thromboembolism	DISUR7CR	Limited	Genetic Variation	[8]

8 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 Cysteine-rich protein 3 (CRIP3).	[9]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cysteine-rich protein 3 (CRIP3).	[11]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cysteine-rich protein 3 (CRIP3).	[12]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cysteine-rich protein 3 (CRIP3).	[13]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Cysteine-rich protein 3 (CRIP3).	[14]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Cysteine-rich protein 3 (CRIP3).	[15]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Cysteine-rich protein 3 (CRIP3).	[16]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cysteine-rich protein 3 (CRIP3).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the methylation of Cysteine-rich protein 3 (CRIP3).	[10]

References

• [1] Identifying Clinical Factors Associated With Low Disease Activity and Remission of Rheumatoid Arthritis During Pregnancy.Arthritis Care Res (Hoboken). 2017 Sep;69(9):1297-1303. doi: 10.1002/acr.23143. Epub 2017 Aug 13.
• [2] The moderate predictive value of serial serum CRP and PCT levels for the prognosis of hospitalized community-acquired pneumonia.Respir Res. 2018 Oct 1;19(1):193. doi: 10.1186/s12931-018-0877-x.
• [3] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [4] Interethnic analyses of blood pressure loci in populations of East Asian and European descent.Nat Commun. 2018 Nov 28;9(1):5052. doi: 10.1038/s41467-018-07345-0.
• [5] Assessment of biological parameters in head and neck cancer based on in vivo distribution of (18)F-FDG-FLT-FMISO-PET/CT images.Tumori. 2020 Feb;106(1):33-38. doi: 10.1177/0300891619868012. Epub 2019 Aug 26.
• [6] Genetic polymorphisms and the risk of stroke after cardiac surgery.Stroke. 2005 Sep;36(9):1854-8. doi: 10.1161/01.STR.0000177482.23478.dc. Epub 2005 Jul 28.
• [7] A low DNA methylation epigenotype in lung squamous cell carcinoma and its association with idiopathic pulmonary fibrosis and poorer prognosis.Int J Cancer. 2020 Jan 15;146(2):388-399. doi: 10.1002/ijc.32532. Epub 2019 Jul 8.
• [8] C-reactive protein 3' UTR +1444C>T polymorphism in patients with spontaneous venous thromboembolism.Atherosclerosis. 2006 Oct;188(2):406-11. doi: 10.1016/j.atherosclerosis.2005.11.006. Epub 2005 Dec 13.
• [9] 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.
• [10] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [11] Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
• [12] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [13] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [14] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [15] Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
• [16] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [17] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.