Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT78DKOU)

• DOT Name: Splicing regulator ARVCF (ARVCF)
• Synonyms: Armadillo repeat protein deleted in velo-cardio-facial syndrome
• Gene Name: ARVCF
• Related Disease:
  Alzheimer disease
  Anorexia nervosa cachexia
  Myocardial infarction
  Prostate cancer
  Prostate carcinoma
  Hirschsprung disease, susceptibility to, 1
  Schizophrenia
• UniProt ID: ARVC_HUMAN
• Pfam ID: PF00514
• Sequence:
  MEDCNVHSAASILASVKEQEARFERLTRALEQERRHVALQLERAQQPGMVSGGMGSGQPL
  PMAWQQLVLQEQSPGSQASLATMPEAPDVLEETVTVEEDPGTPTSHVSIVTSEDGTTRRT
  ETKVTKTVKTVTTRTVRQVPVGPDGLPLLDGGPPLGPFADGALDRHFLLRGGGPVATLSR
  AYLSSGGGFPEGPEPRDSPSYGSLSRGLGMRPPRAGPLGPGPGDGCFTLPGHREAFPVGP
  EPGPPGGRSLPERFQAEPYGLEDDTRSLAADDEGGPELEPDYGTATRRRPECGRGLHTRA
  YEDTADDGGELADERPAFPMVTAPLAQPERGSMGSLDRLVRRSPSVDSARKEPRWRDPEL
  PEVLAMLRHPVDPVKANAAAYLQHLCFENEGVKRRVRQLRGLPLLVALLDHPRAEVRRRA
  CGALRNLSYGRDTDNKAAIRDCGGVPALVRLLRAARDNEVRELVTGTLWNLSSYEPLKMV
  IIDHGLQTLTHEVIVPHSGWEREPNEDSKPRDAEWTTVFKNTSGCLRNVSSDGAEARRRL
  RECEGLVDALLHALQSAVGRKDTDNKSVENCVCIMRNLSYHVHKEVPGADRYQEAEPGPL
  GSAVGSQRRRRDDASCFGGKKAKEEWFHQGKKDGEMDRNFDTLDLPKRTEAAKGFELLYQ
  PEVVRLYLSLLTESRNFNTLEAAAGALQNLSAGNWMWATYIRATVRKERGLPVLVELLQS
  ETDKVVRAVAIALRNLSLDRRNKDLIGSYAMAELVRNVRNAQAPPRPGACLEEDTVVAVL
  NTIHEIVSDSLDNARSLLQARGVPALVALVASSQSVREAKAASHVLQTVWSYKELRGTLQ
  KDGWTKARFQSAAATAKGPKGALSPGGFDDSTLPLVDKSLEGEKTGSRDVIPMDALGPDG
  YSTVDRRERRPRGASSAGEASEKEPLKLDPSRKAPPPGPSRPAVRLVDAVGDAKPQPVDS
  WV
• Function: Contributes to the regulation of alternative splicing of pre-mRNAs.
• Tissue Specificity: Found in all the examined tissues including heart, brain, liver and kidney. Found at low level in lung. Expressed in dermal connective tissue, salivary gland duct and in the corneal layer (at protein level) . Expressed in arrector pili muscle (at protein level) . High levels detected in epithelial cells with lower levels found in fibroblasts and T lymphocytes .

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Anorexia nervosa cachexia	DISFO5RQ	Strong	Biomarker	[2]
Myocardial infarction	DIS655KI	Strong	Genetic Variation	[3]
Prostate cancer	DISF190Y	moderate	Biomarker	[4]
Prostate carcinoma	DISMJPLE	moderate	Biomarker	[4]
Hirschsprung disease, susceptibility to, 1	DISDU2S6	Limited	Biomarker	[5]
Schizophrenia	DISSRV2N	Limited	Biomarker	[6]

5 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 Splicing regulator ARVCF (ARVCF).	[7]
Fulvestrant	DM0YZC6	Approved	Fulvestrant increases the methylation of Splicing regulator ARVCF (ARVCF).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Splicing regulator ARVCF (ARVCF).	[14]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 affects the phosphorylation of Splicing regulator ARVCF (ARVCF).	[16]
Hexadecanoic acid	DMWUXDZ	Investigative	Hexadecanoic acid decreases the phosphorylation of Splicing regulator ARVCF (ARVCF).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Splicing regulator ARVCF (ARVCF).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Splicing regulator ARVCF (ARVCF).	[9]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Splicing regulator ARVCF (ARVCF).	[10]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Splicing regulator ARVCF (ARVCF).	[11]
APR-246	DMNFADH	Phase 2	APR-246 affects the expression of Splicing regulator ARVCF (ARVCF).	[13]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Splicing regulator ARVCF (ARVCF).	[15]

References

• [1] Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer's disease with OSBPL6, PTPRG, and PDCL3.Mol Psychiatry. 2016 Nov;21(11):1608-1612. doi: 10.1038/mp.2015.218. Epub 2016 Feb 2.
• [2] Haplotype analysis of the COMT-ARVCF gene region in Israeli anorexia nervosa family trios.Am J Med Genet B Neuropsychiatr Genet. 2005 Nov 5;139B(1):45-50. doi: 10.1002/ajmg.b.30230.
• [3] Association of a polymorphism of BTN2A1 with myocardial infarction in East Asian populations.Atherosclerosis. 2011 Mar;215(1):145-52. doi: 10.1016/j.atherosclerosis.2010.12.005. Epub 2010 Dec 15.
• [4] Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality.Cancer Epidemiol Biomarkers Prev. 2011 Sep;20(9):1928-36. doi: 10.1158/1055-9965.EPI-11-0236. Epub 2011 Aug 16.
• [5] Exome-Wide Association Study Identified New Risk Loci for Hirschsprung's Disease.Mol Neurobiol. 2017 Apr;54(3):1777-1785. doi: 10.1007/s12035-016-9752-2. Epub 2016 Feb 18.
• [6] The schizophrenia genetics knowledgebase: a comprehensive update of findings from candidate gene studies.Transl Psychiatry. 2019 Aug 27;9(1):205. doi: 10.1038/s41398-019-0532-4.
• [7] 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.
• [8] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [11] Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro. Eur J Nutr. 2005 Mar;44(3):143-56. doi: 10.1007/s00394-004-0503-1. Epub 2004 Apr 30.
• [12] 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.
• [13] 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.
• [14] 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.
• [15] 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.
• [16] 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.
• [17] Functional lipidomics: Palmitic acid impairs hepatocellular carcinoma development by modulating membrane fluidity and glucose metabolism. Hepatology. 2017 Aug;66(2):432-448. doi: 10.1002/hep.29033. Epub 2017 Jun 16.