Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWS63BY)

DOT Name	Vitamin D-binding protein (GC)
Synonyms	DBP; VDB; Gc protein-derived macrophage activating factor; Gc-MAF; GcMAF; Gc-globulin; Group-specific component; Gc; Vitamin D-binding protein-macrophage activating factor; DBP-maf
Gene Name	GC
Related Disease	Lung cancer ( ) Acute kidney injury ( ) Acute liver failure ( ) Acute myocardial infarction ( ) Advanced cancer ( ) Ankylosing spondylitis ( ) Arteriosclerosis ( ) Asthma ( ) Atherosclerosis ( ) Chronic obstructive pulmonary disease ( ) Clear cell renal carcinoma ( ) Colon cancer ( ) Colon carcinoma ( ) Coronary atherosclerosis ( ) Coronary heart disease ( ) Cystic fibrosis ( ) Endometriosis ( ) Hepatic coma ( ) Hepatic encephalopathy ( ) Hepatocellular carcinoma ( ) Liver cancer ( ) Liver cirrhosis ( ) Lung neoplasm ( ) Metabolic bone disease ( ) Neoplasm ( ) Non-alcoholic fatty liver disease ( ) Obesity ( ) Parkinson disease ( ) Renal cell carcinoma ( ) Schizophrenia ( ) Toxic shock syndrome ( ) Type-1 diabetes ( ) Type-1/2 diabetes ( ) Chronic kidney disease ( ) Graves disease ( ) Non-insulin dependent diabetes ( ) Polycystic ovarian syndrome ( ) Vitamin D deficiency ( ) Cutaneous melanoma ( ) Breast cancer ( ) Breast carcinoma ( ) Hepatitis C virus infection ( ) Inflammatory bowel disease ( ) Lupus nephritis ( ) Melanoma ( ) Osteoporosis ( )
UniProt ID	VTDB_HUMAN
3D Structure	Download 2D Sequence (FASTA) Download 3D Structure (PDB) Download
PDB ID	1J78; 1J7E; 1KW2; 1KXP; 1LOT; 1MA9
Pfam ID	PF00273 ; PF09164
Sequence	MKRVLVLLLAVAFGHALERGRDYEKNKVCKEFSHLGKEDFTSLSLVLYSRKFPSGTFEQV SQLVKEVVSLTEACCAEGADPDCYDTRTSALSAKSCESNSPFPVHPGTAECCTKEGLERK LCMAALKHQPQEFPTYVEPTNDEICEAFRKDPKEYANQFMWEYSTNYGQAPLSLLVSYTK SYLSMVGSCCTSASPTVCFLKERLQLKHLSLLTTLSNRVCSQYAAYGEKKSRLSNLIKLA QKVPTADLEDVLPLAEDITNILSKCCESASEDCMAKELPEHTVKLCDNLSTKNSKFEDCC QEKTAMDVFVCTYFMPAAQLPELPDVELPTNKDVCDPGNTKVMDKYTFELSRRTHLPEVF LSKVLEPTLKSLGECCDVEDSTTCFNAKGPLLKKELSSFIDKGQELCADYSENTFTEYKK KLAERLKAKLPDATPTELAKLVNKHSDFASNCCSINSPPLYCDSEIDAELKNIL
Function	Involved in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5 alpha for neutrophils in inflammation and macrophage activation.
Tissue Specificity	Expressed in the liver. Found in plasma, ascites, cerebrospinal fluid and urine.
Reactome Pathway	Vitamin D (calciferol) metabolism (R-HSA-196791 )

Molecular Interaction Atlas (MIA) of This DOT

46 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance
Lung cancer	DISCM4YA	Definitive	Altered Expression	[1]
Acute kidney injury	DISXZG0T	Strong	Biomarker	[2]
Acute liver failure	DIS5EZKX	Strong	Genetic Variation	[3]
Acute myocardial infarction	DISE3HTG	Strong	Genetic Variation	[4]
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[5]
Ankylosing spondylitis	DISRC6IR	Strong	Genetic Variation	[6]
Arteriosclerosis	DISK5QGC	Strong	Genetic Variation	[7]
Asthma	DISW9QNS	Strong	Genetic Variation	[8]
Atherosclerosis	DISMN9J3	Strong	Genetic Variation	[7]
Chronic obstructive pulmonary disease	DISQCIRF	Strong	Genetic Variation	[9]
Clear cell renal carcinoma	DISBXRFJ	Strong	Biomarker	[10]
Colon cancer	DISVC52G	Strong	Biomarker	[11]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[11]
Coronary atherosclerosis	DISKNDYU	Strong	Genetic Variation	[12]
Coronary heart disease	DIS5OIP1	Strong	Genetic Variation	[12]
Cystic fibrosis	DIS2OK1Q	Strong	Biomarker	[13]
Endometriosis	DISX1AG8	Strong	Biomarker	[14]
Hepatic coma	DISILSPO	Strong	Biomarker	[15]
Hepatic encephalopathy	DISEAKAN	Strong	Biomarker	[15]
Hepatocellular carcinoma	DIS0J828	Strong	Biomarker	[16]
Liver cancer	DISDE4BI	Strong	Biomarker	[16]
Liver cirrhosis	DIS4G1GX	Strong	Biomarker	[17]
Lung neoplasm	DISVARNB	Strong	Biomarker	[18]
Metabolic bone disease	DISO7RI8	Strong	Biomarker	[19]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[20]
Non-alcoholic fatty liver disease	DISDG1NL	Strong	Biomarker	[21]
Obesity	DIS47Y1K	Strong	Biomarker	[22]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[23]
Renal cell carcinoma	DISQZ2X8	Strong	Biomarker	[10]
Schizophrenia	DISSRV2N	Strong	Biomarker	[24]
Toxic shock syndrome	DISX5S53	Strong	Biomarker	[25]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[26]
Type-1/2 diabetes	DISIUHAP	Strong	Biomarker	[27]
Chronic kidney disease	DISW82R7	moderate	Biomarker	[28]
Graves disease	DISU4KOQ	moderate	Genetic Variation	[29]
Non-insulin dependent diabetes	DISK1O5Z	moderate	Posttranslational Modification	[30]
Polycystic ovarian syndrome	DISZ2BNG	moderate	Biomarker	[31]
Vitamin D deficiency	DISAWKYI	moderate	Genetic Variation	[32]
Cutaneous melanoma	DIS3MMH9	Disputed	Genetic Variation	[33]
Breast cancer	DIS7DPX1	Limited	Genetic Variation	[34]
Breast carcinoma	DIS2UE88	Limited	Genetic Variation	[34]
Hepatitis C virus infection	DISQ0M8R	Limited	Genetic Variation	[35]
Inflammatory bowel disease	DISGN23E	Limited	Biomarker	[36]
Lupus nephritis	DISCVGPZ	Limited	Biomarker	[37]
Melanoma	DIS1RRCY	Limited	Genetic Variation	[33]
Osteoporosis	DISF2JE0	Limited	Biomarker	[38]
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⏷ Show the Full List of 46 Disease(s)

Molecular Interaction Atlas (MIA)

MIA Detail

Jump to Detail Molecular Interaction Atlas of This DOT

This DOT Affected the Regulation of Drug Effects of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Calcitriol	DM8ZVJ7	Approved	Vitamin D-binding protein (GC) affects the abundance of Calcitriol.	[49]
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This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Cholecalciferol	DMGU74E	Approved	Vitamin D-binding protein (GC) affects the binding of Cholecalciferol.	[50]
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8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Vitamin D-binding protein (GC).	[39]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Vitamin D-binding protein (GC).	[40]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Vitamin D-binding protein (GC).	[41]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Vitamin D-binding protein (GC).	[42]
Ethanol	DMDRQZU	Approved	Ethanol decreases the expression of Vitamin D-binding protein (GC).	[43]
Acocantherin	DM7JT24	Approved	Acocantherin affects the expression of Vitamin D-binding protein (GC).	[44]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Vitamin D-binding protein (GC).	[46]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Vitamin D-binding protein (GC).	[47]
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⏷ Show the Full List of 8 Drug(s)

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Olanzapine	DMPFN6Y	Approved	Olanzapine affects the phosphorylation of Vitamin D-binding protein (GC).	[24]
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1 Drug(s) Affected the Protein Interaction/Cellular Processes of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the binding of Vitamin D-binding protein (GC).	[48]
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References

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4	Vitamin D-binding protein (rs4588) T/T genotype is associated with anteroseptal myocardial infarction in coronary artery disease patients.Ann Transl Med. 2019 Aug;7(16):374. doi: 10.21037/atm.2019.07.49.
5	Association of the vitamin D metabolism gene GC and CYP27B1 polymorphisms with cancer susceptibility: a meta-analysis and trial sequential analysis.Biosci Rep. 2019 Sep 13;39(9):BSR20190368. doi: 10.1042/BSR20190368. Print 2019 Sep 30.
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12	Polymorphisms within vitamin D binding protein gene within a Preeclamptic South African population.Hypertens Pregnancy. 2019 Nov;38(4):260-267. doi: 10.1080/10641955.2019.1667383. Epub 2019 Sep 27.
13	Vitamin D binding protein, a new nutritional marker in cystic fibrosis patients.Clin Chem Lab Med. 2008;46(3):365-70. doi: 10.1515/CCLM.2008.084.
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20	Association of rs2282679 A>C polymorphism in vitamin D binding protein gene with colorectal cancer risk and survival: effect modification by dietary vitamin D intake.BMC Cancer. 2018 Feb 6;18(1):155. doi: 10.1186/s12885-018-4026-1.
21	Association of vitamin D levels and vitamin D-related gene polymorphisms with liver fibrosis in patients with biopsy-proven nonalcoholic fatty liver disease.Dig Liver Dis. 2019 Jul;51(7):1036-1042. doi: 10.1016/j.dld.2018.12.022. Epub 2019 Jan 9.
22	Bioavailable and free 25-hydroxyvitamin D and vitamin D binding protein in polycystic ovary syndrome: Relationships with obesity and insulin resistance.J Steroid Biochem Mol Biol. 2018 Mar;177:209-215. doi: 10.1016/j.jsbmb.2017.07.012. Epub 2017 Jul 19.
23	GC and VDR SNPs and Vitamin D Levels in Parkinson's Disease: The Relevance to Clinical Features.Neuromolecular Med. 2017 Mar;19(1):24-40. doi: 10.1007/s12017-016-8415-9. Epub 2016 Jun 9.
24	Effects of olanzapine on serum protein phosphorylation patterns in patients with schizophrenia. Proteomics Clin Appl. 2015 Oct;9(9-10):907-16. doi: 10.1002/prca.201400148. Epub 2015 May 15.
25	Comparison of rocket and crossed immuno-electrophoresis assays for determination of the level of actin complexing of Gc globulin.Scand J Clin Lab Invest. 2007;67(7):767-77. doi: 10.1080/00365510701326909.
26	Maternal and Newborn Vitamin D-Binding Protein, Vitamin D Levels, Vitamin D Receptor Genotype, and Childhood Type 1 Diabetes.Diabetes Care. 2019 Apr;42(4):553-559. doi: 10.2337/dc18-2176. Epub 2019 Jan 28.
27	Vitamin D-Binding Protein Clearance Ratio Is Significantly Associated with Glycemic Status and Diabetes Complications in a Predominantly Vitamin D-Deficient Population.J Diabetes Res. 2018 May 20;2018:6239158. doi: 10.1155/2018/6239158. eCollection 2018.
28	Fractional excretion as a new marker of tubular damage in children with chronic kidney disease.Clin Chim Acta. 2018 May;480:99-106. doi: 10.1016/j.cca.2018.02.001. Epub 2018 Feb 6.
29	The functional polymorphisms of VDR, GC and CYP2R1 are involved in the pathogenesis of autoimmune thyroid diseases.Clin Exp Immunol. 2014 Nov;178(2):262-9. doi: 10.1111/cei.12420.
30	Methylation in 3' near region of GC gene and its association with the level of vitamin D binding protein and type 2 diabetes mellitus.Nutr Res. 2018 Jun;54:52-59. doi: 10.1016/j.nutres.2018.03.016. Epub 2018 Apr 6.
31	Serum Vitamin D Binding Protein Level Associated with Metabolic Cardiovascular Risk Factors in Women with the Polycystic Ovary Syndrome.Horm Metab Res. 2019 Jan;51(1):54-61. doi: 10.1055/a-0759-7533. Epub 2018 Nov 8.
32	Prevalence of vitamin D deficiency in women from southern Brazil and association with vitamin D-binding protein levels and GC-DBPgene polymorphisms.PLoS One. 2019 Dec 12;14(12):e0226215. doi: 10.1371/journal.pone.0226215. eCollection 2019.
33	Genetic variants in the vitamin D pathway genes VDBP and RXRA modulate cutaneous melanoma disease-specific survival.Pigment Cell Melanoma Res. 2016 Mar;29(2):176-85. doi: 10.1111/pcmr.12437. Epub 2016 Jan 29.
34	Genetic Variants in Group-Specific Component (GC) Gene Are Associated with Breast Cancer Risk among Chinese Women.Biomed Res Int. 2019 Nov 15;2019:3295781. doi: 10.1155/2019/3295781. eCollection 2019.
35	Vitamin D binding protein polymorphisms influence susceptibility to hepatitis C virus infection in a high-risk Chinese population.Gene. 2018 Dec 30;679:405-411. doi: 10.1016/j.gene.2018.09.021. Epub 2018 Sep 12.
36	The Role of Inflammation on Vitamin D Levels in a Cohort of Pediatric Patients With Inflammatory Bowel Disease.J Pediatr Gastroenterol Nutr. 2018 Oct;67(4):501-506. doi: 10.1097/MPG.0000000000002049.
37	Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare.Lupus. 2018 Sep;27(10):1600-1615. doi: 10.1177/0961203318778774. Epub 2018 Jun 29.
38	Serum Proteomic Analysis Reveals Vitamin D-Binding Protein (VDBP) as a Potential Biomarker for Low Bone Mineral Density in Mexican Postmenopausal Women.Nutrients. 2019 Nov 21;11(12):2853. doi: 10.3390/nu11122853.
39	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.
40	Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
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46	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.
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48	Systems toxicology approach explores target-pathway relationship and adverse health impacts of ubiquitous environmental pollutant bisphenol A. J Toxicol Environ Health A. 2022 Mar 19;85(6):217-229. doi: 10.1080/15287394.2021.1994492. Epub 2021 Oct 27.
49	Influence of the vitamin D-binding protein on the serum concentration of 1,25-dihydroxyvitamin D3. Significance of the free 1,25-dihydroxyvitamin D3 concentration. J Clin Invest. 1981 Mar;67(3):589-96. doi: 10.1172/JCI110072.
50	Affinity differences for vitamin D metabolites associated with the genetic isoforms of the human serum carrier protein (DBP). Hum Genet. 1993 Sep;92(2):183-8. doi: 10.1007/BF00219689.