Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2RPM4I)

• DOT Name: Caspase recruitment domain-containing protein 10 (CARD10)
• Synonyms: CARD-containing MAGUK protein 3; Carma 3
• Gene Name: CARD10
• Related Disease:
  Advanced cancer
  Autoimmune hepatitis
  B-cell neoplasm
  Bladder cancer
  Breast cancer
  Breast carcinoma
  Clear cell renal carcinoma
  Colon cancer
  Colon carcinoma
  Colorectal carcinoma
  Crohn disease
  Gastric cancer
  Glioma
  Hepatocellular carcinoma
  Lung cancer
  Lung carcinoma
  Neoplasm
  Non-small-cell lung cancer
  OPTN-related open angle glaucoma
  Ovarian neoplasm
  Pneumonia
  Pneumonitis
  Renal cell carcinoma
  Stomach cancer
  Urinary bladder cancer
  Urinary bladder neoplasm
  Metastatic malignant neoplasm
  Asthma
  Immunodeficiency 89 and autoimmunity
• UniProt ID: CAR10_HUMAN
• Pfam ID: PF00619
• Sequence:
  MPGRAEAGEAEEEAGAGSGSEAEEDALWERIEGVRHRLARALNPAKLTPYLRQCRVIDEQ
  DEEEVLSTYRFPCRVNRTGRLMDILRCRGKRGYEAFLEALEFYYPEHFTLLTGQEPAQRC
  SMILDEEGPEGLTQFLMTEVRRLREARKSQLQREQQLQARGRVLEEERAGLEQRLRDQQQ
  AQERCQRLREDWEAGSLELLRLKDENYMIAMRLAQLSEEKNSAVLRSRDLQLAVDQLKLK
  VSRLEEECALLRRARGPPPGAEEKEKEKEKEKEPDNVDLVSELRAENQRLTASLRELQEG
  LQQEASRPGAPGSERILLDILEHDWREAQDSRQELCQKLHAVQGELQWAEELRDQYLQEM
  EDLRLKHRTLQKDCDLYKHRMATVLAQLEEIEKERDQAIQSRDRIQLQYSQSLIEKDQYR
  KQVRGLEAERDELLTTLTSLEGTKALLEVQLQRAQGGTCLKACASSHSLCSNLSSTWSLS
  EFPSPLGGPEATGEAAVMGGPEPHNSEEATDSEKEINRLSILPFPPSAGSILRRQREEDP
  APPKRSFSSMSDITGSVTLKPWSPGLSSSSSSDSVWPLGKPEGLLARGCGLDFLNRSLAI
  RVSGRSPPGGPEPQDKGPDGLSFYGDRWSGAVVRRVLSGPGSARMEPREQRVEAAGLEGA
  CLEAEAQQRTLLWNQGSTLPSLMDSKACQSFHEALEAWAKGPGAEPFYIRANLTLPERAD
  PHALCVKAQEILRLVDSAYKRRQEWFCTRVDPLTLRDLDRGTVPNYQRAQQLLEVQEKCL
  PSSRHRGPRSNLKKRALDQLRLVRPKPVGAPAGDSPDQLLLEPCAEPERSLRPYSLVRPL
  LVSALRPVVLLPECLAPRLIRNLLDLPSSRLDFQVCPAESLSGEELCPSSAPGAPKAQPA
  TPGLGSRIRAIQESVGKKHCLLELGARGVRELVQNEIYPIVIHVEVTEKNVREVRGLLGR
  PGWRDSELLRQCRGSEQVLWGLPCSWVQVPAHEWGHAEELAKVVRGRILQEQARLVWVEC
  GSSRGCPSSSEA
• Function: Scaffold protein that plays an important role in mediating the activation of NF-kappa-B via BCL10 or EGFR.
• Tissue Specificity: Detected in adult heart, kidney and liver; lower levels in intestine, placenta, muscle and lung. Also found in fetal lung, liver and kidney.
• KEGG Pathway: NF-kappa B sig.ling pathway (hsa04064)

Molecular Interaction Atlas (MIA) of This DOT

29 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Biomarker	[1]
Autoimmune hepatitis	DISOX03Q	Strong	Genetic Variation	[2]
B-cell neoplasm	DISVY326	Strong	Genetic Variation	[3]
Bladder cancer	DISUHNM0	Strong	Biomarker	[4]
Breast cancer	DIS7DPX1	Strong	Biomarker	[5]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[5]
Clear cell renal carcinoma	DISBXRFJ	Strong	Altered Expression	[6]
Colon cancer	DISVC52G	Strong	Altered Expression	[7]
Colon carcinoma	DISJYKUO	Strong	Altered Expression	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[8]
Crohn disease	DIS2C5Q8	Strong	Altered Expression	[9]
Gastric cancer	DISXGOUK	Strong	Biomarker	[10]
Glioma	DIS5RPEH	Strong	Biomarker	[11]
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[12]
Lung cancer	DISCM4YA	Strong	Altered Expression	[13]
Lung carcinoma	DISTR26C	Strong	Altered Expression	[13]
Neoplasm	DISZKGEW	Strong	Biomarker	[14]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Altered Expression	[13]
OPTN-related open angle glaucoma	DISDR98A	Strong	SusceptibilityMutation	[15]
Ovarian neoplasm	DISEAFTY	Strong	Biomarker	[16]
Pneumonia	DIS8EF3M	Strong	Biomarker	[17]
Pneumonitis	DIS88E0K	Strong	Biomarker	[17]
Renal cell carcinoma	DISQZ2X8	Strong	Altered Expression	[6]
Stomach cancer	DISKIJSX	Strong	Biomarker	[10]
Urinary bladder cancer	DISDV4T7	Strong	Biomarker	[4]
Urinary bladder neoplasm	DIS7HACE	Strong	Biomarker	[4]
Metastatic malignant neoplasm	DIS86UK6	moderate	Altered Expression	[18]
Asthma	DISW9QNS	Limited	Biomarker	[19]
Immunodeficiency 89 and autoimmunity	DISKKZ45	Limited	Unknown	[20]

18 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 Caspase recruitment domain-containing protein 10 (CARD10).	[21]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[22]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[23]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[24]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[25]
Arsenic	DMTL2Y1	Approved	Arsenic increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[26]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[27]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[28]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[29]
Etoposide	DMNH3PG	Approved	Etoposide increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[25]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[30]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[31]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[32]
Belinostat	DM6OC53	Phase 2	Belinostat decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[31]
APR-246	DMNFADH	Phase 2	APR-246 increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[33]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[34]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[35]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Caspase recruitment domain-containing protein 10 (CARD10).	[32]

References

• [1] Caspase recruitment domain family member 10 regulates carbamoyl phosphate synthase 1 and promotes cancer growth in bladder cancer cells.J Cell Mol Med. 2019 Dec;23(12):8128-8138. doi: 10.1111/jcmm.14683. Epub 2019 Sep 29.
• [2] Genome-wide association study identifies variants associated with autoimmune hepatitis type 1.Gastroenterology. 2014 Aug;147(2):443-52.e5. doi: 10.1053/j.gastro.2014.04.022. Epub 2014 Apr 23.
• [3] Genetic errors of the human caspase recruitment domain-B-cell lymphoma 10-mucosa-associated lymphoid tissue lymphoma-translocation gene 1 (CBM) complex: Molecular, immunologic, and clinical heterogeneity.J Allergy Clin Immunol. 2015 Nov;136(5):1139-49. doi: 10.1016/j.jaci.2015.06.031. Epub 2015 Aug 12.
• [4] The circINTS4/miR-146b/CARMA3 axis promotes tumorigenesis in bladder cancer.Cancer Gene Ther. 2020 Apr;27(3-4):189-202. doi: 10.1038/s41417-019-0085-y. Epub 2019 Feb 6.
• [5] Epigenetic inactivation of the splicing RNA-binding protein CELF2 in human breast cancer.Oncogene. 2019 Nov;38(45):7106-7112. doi: 10.1038/s41388-019-0936-x. Epub 2019 Aug 13.
• [6] Evaluating the expression of CARMA3 as a prognostic tumor marker in renal cell carcinoma.Tumour Biol. 2013 Dec;34(6):3431-5. doi: 10.1007/s13277-013-0917-6. Epub 2013 Jun 15.
• [7] CARMA3 is overexpressed in colon cancer and regulates NF-B activity and cyclin D1 expression.Biochem Biophys Res Commun. 2012 Sep 7;425(4):781-7. doi: 10.1016/j.bbrc.2012.07.152. Epub 2012 Aug 2.
• [8] MicroRNA-195 inhibits colorectal cancer cell proliferation, colony-formation and invasion through targeting CARMA3.Mol Med Rep. 2014 Jul;10(1):473-8. doi: 10.3892/mmr.2014.2178. Epub 2014 Apr 24.
• [9] Caspase recruitment domain (CARD) family (CARD9, CARD10, CARD11, CARD14 and CARD15) are increased during active inflammation in patients with inflammatory bowel disease.J Inflamm (Lond). 2018 Jul 11;15:13. doi: 10.1186/s12950-018-0189-4. eCollection 2018.
• [10] microRNA-146a inhibits G protein-coupled receptor-mediated activation of NF-B by targeting CARD10 and COPS8 in gastric cancer.Mol Cancer. 2012 Sep 20;11:71. doi: 10.1186/1476-4598-11-71.
• [11] CARMA3 is overexpressed in human glioma and promotes cell invasion through MMP9 regulation in A172 cell line.Tumour Biol. 2014 Jan;35(1):149-54. doi: 10.1007/s13277-013-1018-2. Epub 2013 Jul 27.
• [12] CARMA3/NF-B signaling contributes to tumorigenesis of hepatocellular carcinoma and is inhibited by sodium aescinate.World J Gastroenterol. 2019 Sep 28;25(36):5483-5493. doi: 10.3748/wjg.v25.i36.5483.
• [13] Overexpression of CARMA3 in non-small-cell lung cancer is linked for tumor progression.PLoS One. 2012;7(5):e36903. doi: 10.1371/journal.pone.0036903. Epub 2012 May 15.
• [14] Silencing of CARMA3 inhibits bladder cancer cell migration and invasion via deactivating -catenin signaling pathway.Onco Targets Ther. 2019 Aug 9;12:6309-6322. doi: 10.2147/OTT.S191502. eCollection 2019.
• [15] Rare variants in optic disc area gene CARD10 enriched in primary open-angle glaucoma.Mol Genet Genomic Med. 2016 Oct 3;4(6):624-633. doi: 10.1002/mgg3.248. eCollection 2016 Nov.
• [16] Protein kinase C alpha-CARMA3 signaling axis links Ras to NF-kappa B for lysophosphatidic acid-induced urokinase plasminogen activator expression in ovarian cancer cells.Oncogene. 2008 Feb 21;27(9):1273-80. doi: 10.1038/sj.onc.1210746. Epub 2007 Aug 27.
• [17] CARMA3 Mediates Allergic Lung Inflammation in Response to Alternaria alternata.Am J Respir Cell Mol Biol. 2018 Dec;59(6):684-694. doi: 10.1165/rcmb.2017-0181OC.
• [18] The CBM Complex Underwrites NF-B Activation to Promote HER2-Associated Tumor Malignancy.Mol Cancer Res. 2016 Jan;14(1):93-102. doi: 10.1158/1541-7786.MCR-15-0229-T. Epub 2015 Sep 21.
• [19] CARMA3 mediates lysophosphatidic acid-stimulated cytokine secretion by bronchial epithelial cells.Am J Respir Cell Mol Biol. 2009 Mar;40(3):286-94. doi: 10.1165/rcmb.2008-0129OC. Epub 2008 Aug 28.
• [20] Mutant CARD10 in a family with progressive immunodeficiency and autoimmunity. Cell Mol Immunol. 2020 Jul;17(7):782-784. doi: 10.1038/s41423-020-0423-x. Epub 2020 Apr 1.
• [21] The neuroprotective action of the mood stabilizing drugs lithium chloride and sodium valproate is mediated through the up-regulation of the homeodomain protein Six1. Toxicol Appl Pharmacol. 2009 Feb 15;235(1):124-34.
• [22] 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.
• [23] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [24] 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.
• [25] Estrogen regulation of apoptosis in osteoblasts. Physiol Behav. 2010 Feb 9;99(2):181-5. doi: 10.1016/j.physbeh.2009.04.025. Epub 2009 May 5.
• [26] Genome-wide analysis of BEAS-2B cells exposed to trivalent arsenicals and dimethylthioarsinic acid. Toxicology. 2010 Jan 31;268(1-2):31-9.
• [27] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [28] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [29] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [30] Repurposing L-menthol for systems medicine and cancer therapeutics? L-menthol induces apoptosis through caspase 10 and by suppressing HSP90. OMICS. 2016 Jan;20(1):53-64.
• [31] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [32] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [33] Mutant p53 reactivation by PRIMA-1MET induces multiple signaling pathways converging on apoptosis. Oncogene. 2010 Mar 4;29(9):1329-38. doi: 10.1038/onc.2009.425. Epub 2009 Nov 30.
• [34] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [35] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.