Details of Drug Off-Target (DOT)

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

• DOT Name: Ceramide transfer protein (CERT1)
• Synonyms: hCERT; Collagen type IV alpha-3-binding protein; Goodpasture antigen-binding protein; GPBP; START domain-containing protein 11; StARD11; StAR-related lipid transfer protein 11
• Gene Name: CERT1
• Related Disease:
  Intellectual disability, autosomal dominant 40
  Advanced cancer
  Alzheimer disease
  Atrial fibrillation
  Autoimmune disease
  Breast cancer
  Breast carcinoma
  Cardiac failure
  Cardiovascular disease
  Epilepsy
  Glomerulonephritis
  Intellectual disability
  Intellectual disability, autosomal dominant 34
  Neurodevelopmental disorder
  Non-small-cell lung cancer
  Stroke
  Type-1/2 diabetes
  Epithelial ovarian cancer
  Ovarian cancer
  Ovarian neoplasm
• UniProt ID: CERT_HUMAN
• PDB ID: 2E3M; 2E3N; 2E3O; 2E3P; 2E3Q; 2E3R; 2E3S; 2RSG; 2Z9Y; 2Z9Z; 3H3Q; 3H3R; 3H3S; 3H3T; 4HHV; 5JJD; 5ZYG; 5ZYH; 5ZYI; 5ZYJ; 5ZYK; 5ZYL; 5ZYM; 6IEZ; 6IF0; 6J0O; 6J81
• Pfam ID: PF00169 ; PF01852
• Sequence:
  MSDNQSWNSSGSEEDPETESGPPVERCGVLSKWTNYIHGWQDRWVVLKNNALSYYKSEDE
  TEYGCRGSICLSKAVITPHDFDECRFDISVNDSVWYLRAQDPDHRQQWIDAIEQHKTESG
  YGSESSLRRHGSMVSLVSGASGYSATSTSSFKKGHSLREKLAEMETFRDILCRQVDTLQK
  YFDACADAVSKDELQRDKVVEDDEDDFPTTRSDGDFLHSTNGNKEKLFPHVTPKGINGID
  FKGEAITFKATTAGILATLSHCIELMVKREDSWQKRLDKETEKKRRTEEAYKNAMTELKK
  KSHFGGPDYEEGPNSLINEEEFFDAVEAALDRQDKIEEQSQSEKVRLHWPTSLPSGDAFS
  SVGTHRFVQKPYSRSSSMSSIDLVSASDDVHRFSSQVEEMVQNHMTYSLQDVGGDANWQL
  VVEEGEMKVYRREVEENGIVLDPLKATHAVKGVTGHEVCNYFWNVDVRNDWETTIENFHV
  VETLADNAIIIYQTHKRVWPASQRDVLYLSVIRKIPALTENDPETWIVCNFSVDHDSAPL
  NNRCVRAKINVAMICQTLVSPPEGNQEISRDNILCKITYVANVNPGGWAPASVLRAVAKR
  EYPKFLKRFTSYVQEKTAGKPILF
• Function: Shelters ceramides and diacylglycerol lipids inside its START domain and mediates the intracellular trafficking of ceramides and diacylglycerol lipids in a non-vesicular manner.
• Tissue Specificity: Widely expressed.

Molecular Interaction Atlas (MIA) of This DOT

20 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Intellectual disability, autosomal dominant 40	DISAI0IH	Definitive	Autosomal dominant	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Atrial fibrillation	DIS15W6U	Strong	Genetic Variation	[4]
Autoimmune disease	DISORMTM	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Altered Expression	[6]
Breast carcinoma	DIS2UE88	Strong	Altered Expression	[6]
Cardiac failure	DISDC067	Strong	Genetic Variation	[4]
Cardiovascular disease	DIS2IQDX	Strong	Genetic Variation	[7]
Epilepsy	DISBB28L	Strong	Biomarker	[8]
Glomerulonephritis	DISPZIQ3	Strong	Biomarker	[9]
Intellectual disability	DISMBNXP	Strong	Biomarker	[1]
Intellectual disability, autosomal dominant 34	DISZXLIC	Strong	Autosomal dominant	[10]
Neurodevelopmental disorder	DIS372XH	Strong	Biomarker	[8]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[11]
Stroke	DISX6UHX	Strong	Genetic Variation	[4]
Type-1/2 diabetes	DISIUHAP	Strong	Genetic Variation	[4]
Epithelial ovarian cancer	DIS56MH2	moderate	Altered Expression	[12]
Ovarian cancer	DISZJHAP	moderate	Altered Expression	[12]
Ovarian neoplasm	DISEAFTY	moderate	Altered Expression	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Gefitinib	DM15F0X	Approved	Ceramide transfer protein (CERT1) affects the response to substance of Gefitinib.	[11]

12 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 Ceramide transfer protein (CERT1).	[13]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Ceramide transfer protein (CERT1).	[14]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Ceramide transfer protein (CERT1).	[15]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ceramide transfer protein (CERT1).	[16]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Ceramide transfer protein (CERT1).	[17]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Ceramide transfer protein (CERT1).	[18]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Ceramide transfer protein (CERT1).	[19]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Ceramide transfer protein (CERT1).	[21]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Ceramide transfer protein (CERT1).	[21]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Ceramide transfer protein (CERT1).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Ceramide transfer protein (CERT1).	[23]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Ceramide transfer protein (CERT1).	[26]

3 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 Ceramide transfer protein (CERT1).	[20]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Ceramide transfer protein (CERT1).	[24]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Ceramide transfer protein (CERT1).	[25]

References

• [1] Large-scale discovery of novel genetic causes of developmental disorders. Nature. 2015 Mar 12;519(7542):223-8. doi: 10.1038/nature14135. Epub 2014 Dec 24.
• [2] N,O-Dialkyl deoxynojirimycin derivatives as CERT START domain ligands.Bioorg Med Chem Lett. 2020 Jan 15;30(2):126796. doi: 10.1016/j.bmcl.2019.126796. Epub 2019 Nov 9.
• [3] Goodpasture antigen-binding protein/ceramide transporter binds to human serum amyloid P-component and is present in brain amyloid plaques.J Biol Chem. 2012 Apr 27;287(18):14897-911. doi: 10.1074/jbc.M111.299545. Epub 2012 Mar 6.
• [4] Pleiotropic Meta-Analyses of Longitudinal Studies Discover Novel Genetic Variants Associated with Age-Related Diseases.Front Genet. 2016 Oct 13;7:179. doi: 10.3389/fgene.2016.00179. eCollection 2016.
• [5] The ceramide transporter and the Goodpasture antigen binding protein: one protein--one function?.J Neurochem. 2010 Jun;113(6):1369-86. doi: 10.1111/j.1471-4159.2010.06673.x. Epub 2010 Mar 17.
• [6] Loss of the ceramide transfer protein augments EGF receptor signaling in breast cancer.Cancer Res. 2012 Jun 1;72(11):2855-66. doi: 10.1158/0008-5472.CAN-11-3069. Epub 2012 Apr 3.
• [7] 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.
• [8] De novo variants in neurodevelopmental disorders with epilepsy.Nat Genet. 2018 Jul;50(7):1048-1053. doi: 10.1038/s41588-018-0143-7. Epub 2018 Jun 25.
• [9] Increased Goodpasture antigen-binding protein expression induces type IV collagen disorganization and deposit of immunoglobulin A in glomerular basement membrane.Am J Pathol. 2007 Nov;171(5):1419-30. doi: 10.2353/ajpath.2007.070205. Epub 2007 Oct 4.
• [10] Diagnostic exome sequencing in persons with severe intellectual disability. N Engl J Med. 2012 Nov 15;367(20):1921-9. doi: 10.1056/NEJMoa1206524. Epub 2012 Oct 3.
• [11] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.
• [12] Regulators of mitotic arrest and ceramide metabolism are determinants of sensitivity to paclitaxel and other chemotherapeutic drugs.Cancer Cell. 2007 Jun;11(6):498-512. doi: 10.1016/j.ccr.2007.04.011.
• [13] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [14] 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.
• [15] Increased mitochondrial ROS formation by acetaminophen in human hepatic cells is associated with gene expression changes suggesting disruption of the mitochondrial electron transport chain. Toxicol Lett. 2015 Apr 16;234(2):139-50.
• [16] 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.
• [17] Extremely low copper concentrations affect gene expression profiles of human prostate epithelial cell lines. Chem Biol Interact. 2010 Oct 6;188(1):214-9.
• [18] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [19] 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.
• [20] 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.
• [21] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [22] Transcriptional signature of human macrophages exposed to the environmental contaminant benzo(a)pyrene. Toxicol Sci. 2010 Apr;114(2):247-59.
• [23] 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.
• [24] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [25] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [26] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [27] Prediction of sensitivity of advanced non-small cell lung cancers to gefitinib (Iressa, ZD1839). Hum Mol Genet. 2004 Dec 15;13(24):3029-43. doi: 10.1093/hmg/ddh331. Epub 2004 Oct 20.