Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT57EPQC)

• DOT Name: Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6)
• Gene Name: C1QTNF6
• Related Disease:
  Arteriosclerosis
  Atherosclerosis
  Autoimmune disease
  Autoimmune disease, susceptibility to, 6
  Hereditary hemochromatosis
  Hypothyroidism
  Lentivirus infection
  Multiple sclerosis
  Renal fibrosis
  Rheumatoid arthritis
  STAT3-related early-onset multisystem autoimmune disease
  Stomach cancer
  Type-1 diabetes
  Vitiligo
  Cardiovascular disease
  Hepatocellular carcinoma
  High blood pressure
  Arthritis
  Enterovirus infection
  Graves disease
  Nervous system inflammation
  Obesity
  Systemic lupus erythematosus
• UniProt ID: C1QT6_HUMAN
• Pfam ID: PF00386 ; PF01391
• Sequence:
  MQWLRVRESPGEATGHRVTMGTAALGPVWAALLLFLLMCEIPMVELTFDRAVASGCQRCC
  DSEDPLDPAHVSSASSSGRPHALPEIRPYINITILKGDKGDPGPMGLPGYMGREGPQGEP
  GPQGSKGDKGEMGSPGAPCQKRFFAFSVGRKTALHSGEDFQTLLFERVFVNLDGCFDMAT
  GQFAAPLRGIYFFSLNVHSWNYKETYVHIMHNQKEAVILYAQPSERSIMQSQSVMLDLAY
  GDRVWVRLFKRQRENAIYSNDFDTYITFSGHLIKAEDD

Molecular Interaction Atlas (MIA) of This DOT

23 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Arteriosclerosis	DISK5QGC	Strong	Biomarker	[1]
Atherosclerosis	DISMN9J3	Strong	Biomarker	[1]
Autoimmune disease	DISORMTM	Strong	Genetic Variation	[2]
Autoimmune disease, susceptibility to, 6	DISHNUXI	Strong	Genetic Variation	[2]
Hereditary hemochromatosis	DISVG5MT	Strong	Biomarker	[3]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[2]
Lentivirus infection	DISX17PY	Strong	Biomarker	[4]
Multiple sclerosis	DISB2WZI	Strong	Genetic Variation	[5]
Renal fibrosis	DISMHI3I	Strong	Biomarker	[6]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[7]
STAT3-related early-onset multisystem autoimmune disease	DISAXTN7	Strong	Genetic Variation	[2]
Stomach cancer	DISKIJSX	Strong	Biomarker	[4]
Type-1 diabetes	DIS7HLUB	Strong	Genetic Variation	[8]
Vitiligo	DISR05SL	Strong	Genetic Variation	[9]
Cardiovascular disease	DIS2IQDX	moderate	Biomarker	[10]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[11]
High blood pressure	DISY2OHH	moderate	Altered Expression	[12]
Arthritis	DIST1YEL	Limited	Biomarker	[7]
Enterovirus infection	DISH2UDP	Limited	Genetic Variation	[13]
Graves disease	DISU4KOQ	Limited	Genetic Variation	[14]
Nervous system inflammation	DISB3X5A	Limited	Biomarker	[7]
Obesity	DIS47Y1K	Limited	Biomarker	[15]
Systemic lupus erythematosus	DISI1SZ7	Limited	Genetic Variation	[16]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[23]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[20]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[19]
Zoledronate	DMIXC7G	Approved	Zoledronate decreases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[21]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[22]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[24]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[25]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde decreases the expression of Complement C1q tumor necrosis factor-related protein 6 (C1QTNF6).	[26]

References

• [1] Flavone of Hippophae (H-flavone) lowers atherosclerotic risk factors via upregulation of the adipokine C1q/tumor necrosis factor-related protein 6 (CTRP6) in macrophages.Biosci Biotechnol Biochem. 2019 Nov;83(11):2000-2007. doi: 10.1080/09168451.2019.1634997. Epub 2019 Jun 28.
• [2] 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.
• [3] Lentivirus-mediated CTRP6 silencing ameliorates diet-induced obesity in mice.Exp Cell Res. 2018 Jun 1;367(1):15-23. doi: 10.1016/j.yexcr.2018.01.027. Epub 2018 Jan 31.
• [4] C1QTNF6 is overexpressed in gastric carcinoma and contributes to the proliferation and migration of gastric carcinoma cells.Int J Mol Med. 2019 Jan;43(1):621-629. doi: 10.3892/ijmm.2018.3978. Epub 2018 Nov 6.
• [5] Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci.Ann Neurol. 2011 Dec;70(6):897-912. doi: 10.1002/ana.22609.
• [6] CTRP6 inhibits cell proliferation and ECM expression in rat mesangial cells cultured under TGF-1.Biomed Pharmacother. 2018 Jan;97:280-285. doi: 10.1016/j.biopha.2017.10.091. Epub 2017 Nov 6.
• [7] CTRP6 is an endogenous complement regulator that can effectively treat induced arthritis.Nat Commun. 2015 Sep 25;6:8483. doi: 10.1038/ncomms9483.
• [8] Fine mapping of type 1 diabetes susceptibility loci and evidence for colocalization of causal variants with lymphoid gene enhancers.Nat Genet. 2015 Apr;47(4):381-6. doi: 10.1038/ng.3245. Epub 2015 Mar 9.
• [9] Genome-wide association studies of autoimmune vitiligo identify 23 new risk loci and highlight key pathways and regulatory variants.Nat Genet. 2016 Nov;48(11):1418-1424. doi: 10.1038/ng.3680. Epub 2016 Oct 10.
• [10] C1qTNF-related protein-6 protects against doxorubicin-induced cardiac injury.J Cell Biochem. 2019 Jun;120(6):10748-10755. doi: 10.1002/jcb.28366. Epub 2019 Feb 5.
• [11] Inhibition of CTRP6 prevented survival and migration in hepatocellular carcinoma through inactivating the AKT signaling pathway.J Cell Biochem. 2019 Oct;120(10):17059-17066. doi: 10.1002/jcb.28967. Epub 2019 May 20.
• [12] Adipokine CTRP6 improves PPAR activation to alleviate angiotensin II-induced hypertension and vascular endothelial dysfunction in spontaneously hypertensive rats.Biochem Biophys Res Commun. 2017 Jan 22;482(4):727-734. doi: 10.1016/j.bbrc.2016.11.102. Epub 2016 Nov 18.
• [13] Genetic Determinants of Enterovirus Infections: Polymorphisms in Type 1 Diabetes and Innate Immune Genes in the MIDIA Study.Viral Immunol. 2015 Dec;28(10):556-63. doi: 10.1089/vim.2015.0067. Epub 2015 Oct 20.
• [14] Association Analysis of Single Nucleotide Polymorphisms in C1QTNF6, RAC2, and an Intergenic Region at 14q32.2 with Graves' Disease in Chinese Han Population.Genet Test Mol Biomarkers. 2017 Aug;21(8):479-484. doi: 10.1089/gtmb.2017.0009. Epub 2017 Jun 30.
• [15] Circulating CTRP6 Levels are Increased in Overweight or Obese Chinese Individuals and Associated with Insulin Resistance Parameters: A Pilot Study.Exp Clin Endocrinol Diabetes. 2021 Jul;129(7):535-541. doi: 10.1055/a-0929-6072. Epub 2019 Aug 14.
• [16] Transancestral mapping and genetic load in systemic lupus erythematosus.Nat Commun. 2017 Jul 17;8:16021. doi: 10.1038/ncomms16021.
• [17] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [18] 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.
• [19] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [20] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [21] Interleukin-19 as a translational indicator of renal injury. Arch Toxicol. 2015 Jan;89(1):101-6.
• [22] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [23] 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.
• [24] 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.
• [25] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
• [26] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.