Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4PTCTF)

• DOT Name: Adhesion G protein-coupled receptor F4 (ADGRF4)
• Synonyms: G-protein coupled receptor 115; G-protein coupled receptor PGR18
• Gene Name: ADGRF4
• Related Disease:
  Lung squamous cell carcinoma
  Advanced cancer
  Schizophrenia
• UniProt ID: AGRF4_HUMAN
• Pfam ID: PF00002 ; PF01825
• Sequence:
  MKMKSQATMICCLVFFLSTECSHYRSKIHLKAGDKLQSPEGKPKTGRIQEKCEGPCISSS
  NCSQPCAKDFHGEIGFTCNQKKWQKSAETCTSLSVEKLFKDSTGASRLSVAAPSIPLHIL
  DFRAPETIESVAQGIRKNCPFDYACITDMVKSSETTSGNIAFIVELLKNISTDLSDNVTR
  EKMKSYSEVANHILDTAAISNWAFIPNKNASSDLLQSVNLFARQLHIHNNSENIVNELFI
  QTKGFHINHNTSEKSLNFSMSMNNTTEDILGMVQIPRQELRKLWPNASQAISIAFPTLGA
  ILREAHLQNVSLPRQVNGLVLSVVLPERLQEIILTFEKINKTRNARAQCVGWHSKKRRWD
  EKACQMMLDIRNEVKCRCNYTSVVMSFSILMSSKSMTDKVLDYITCIGLSVSILSLVLCL
  IIEATVWSRVVVTEISYMRHVCIVNIAVSLLTANVWFIIGSHFNIKAQDYNMCVAVTFFS
  HFFYLSLFFWMLFKALLIIYGILVIFRRMMKSRMMVIGFAIGYGCPLIIAVTTVAITEPE
  KGYMRPEACWLNWDNTKALLAFAIPAFVIVAVNLIVVLVVAVNTQRPSIGSSKSQDVVII
  MRISKNVAILTPLLGLTWGFGIATLIEGTSLTFHIIFALLNAFQGFFILLFGTIMDHKIR
  DALRMRMSSLKGKSRAAENASLGPTNGSKLMNRQG
• Function: Orphan receptor.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lung squamous cell carcinoma	DISXPIBD	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Biomarker	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adhesion G protein-coupled receptor F4 (ADGRF4).	[4]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Adhesion G protein-coupled receptor F4 (ADGRF4).	[5]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Adhesion G protein-coupled receptor F4 (ADGRF4).	[6]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Adhesion G protein-coupled receptor F4 (ADGRF4).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Adhesion G protein-coupled receptor F4 (ADGRF4).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Adhesion G protein-coupled receptor F4 (ADGRF4).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Adhesion G protein-coupled receptor F4 (ADGRF4).	[8]

References

• [1] TRIM58/cg26157385 methylation is associated with eight prognostic genes in lung squamous cell carcinoma.Oncol Rep. 2018 Jul;40(1):206-216. doi: 10.3892/or.2018.6426. Epub 2018 May 8.
• [2] Analysis of the interplay between methylation and expression reveals its potential role in cancer aetiology.Funct Integr Genomics. 2017 Jan;17(1):53-68. doi: 10.1007/s10142-016-0533-9. Epub 2016 Nov 7.
• [3] Exome sequencing supports a de novo mutational paradigm for schizophrenia.Nat Genet. 2011 Aug 7;43(9):864-8. doi: 10.1038/ng.902.
• [4] 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.
• [5] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [6] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [7] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [8] 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.
• [9] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.