Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTJHEFE5)

• DOT Name: F-box only protein 15 (FBXO15)
• Gene Name: FBXO15
• Related Disease:
  Autism
  Invasive aspergillosis
  Meningococcal disease
  Narcolepsy
  Venous thromboembolism
  Pneumonia
  Tourette syndrome
• UniProt ID: FBX15_HUMAN
• Pfam ID: PF12937
• Sequence:
  MATGRGRILQQHWLGLQTLRGPSRGGGAARGRARAFGCRKGPGVKLSAGSAALRCHAGGG
  QHWESSFSCCSGFLDGMPSEILLKIFSYLDAVSLLCTGCVSRRFYHLANDNFIWIGIYST
  AFSPARSNWKFNSVEKIAMSMSFLSVQDKEAGYWKKEYITKQIASVKAALADILKPVNPY
  TGLPVKTKEALRIFGLGWAIILKEKGGKEYIMEHVDLSINDTSVTVIWYGKKWPCLASLS
  TLDLCGMTPVFTDWYKTPTKHRLRWHSLIAKYNLSHLTISTMIGCDRLIRIFCLHPGLLV
  GVWKKEEELAFVMANLHFHHLVERSTLGSATIPYELPPHSPFLDDSPEYGLHGYQLHVDL
  HSGGVFYLCGTFRNLFTKRGNIENGHVKLIVIHLKNNREHLPLIGKVGLSWKTDIFDGCI
  KSCSMMDVTLLDEHGKPFWCFSSPVCLRSPATPSDSSSFLGQTYNVDYVDAEGRVHVELV
  WIRETEEYLIVNLVLYLSIAKINHWFGTEY
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Invasive aspergillosis	DISAI029	Strong	Altered Expression	[2]
Meningococcal disease	DISGDM2Z	Strong	Genetic Variation	[3]
Narcolepsy	DISLCNLI	moderate	Genetic Variation	[4]
Venous thromboembolism	DISUR7CR	moderate	Genetic Variation	[5]
Pneumonia	DIS8EF3M	Limited	Biomarker	[6]
Tourette syndrome	DISX9D54	No Known	Unknown	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of F-box only protein 15 (FBXO15).	[8]

5 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 F-box only protein 15 (FBXO15).	[9]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of F-box only protein 15 (FBXO15).	[10]
Rosiglitazone	DMILWZR	Approved	Rosiglitazone increases the expression of F-box only protein 15 (FBXO15).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of F-box only protein 15 (FBXO15).	[12]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of F-box only protein 15 (FBXO15).	[13]

References

• [1] Genetic determinants of autism in individuals with deletions of 18q.Hum Genet. 2010 Aug;128(2):155-64. doi: 10.1007/s00439-010-0839-y. Epub 2010 May 25.
• [2] SCF Ubiquitin Ligase F-box Protein Fbx15 Controls Nuclear Co-repressor Localization, Stress Response and Virulence of the Human Pathogen Aspergillus fumigatus.PLoS Pathog. 2016 Sep 20;12(9):e1005899. doi: 10.1371/journal.ppat.1005899. eCollection 2016 Sep.
• [3] Genome-wide association study identifies variants in the CFH region associated with host susceptibility to meningococcal disease.Nat Genet. 2010 Sep;42(9):772-6. doi: 10.1038/ng.640. Epub 2010 Aug 8.
• [4] Using the Coriell Personalized Medicine Collaborative Data to conduct a genome-wide association study of sleep duration.Am J Med Genet B Neuropsychiatr Genet. 2015 Dec;168(8):697-705. doi: 10.1002/ajmg.b.32362. Epub 2015 Sep 3.
• [5] A genome-wide search for common SNP x SNP interactions on the risk of venous thrombosis.BMC Med Genet. 2013 Mar 20;14:36. doi: 10.1186/1471-2350-14-36.
• [6] E3 ligase subunit Fbxo15 and PINK1 kinase regulate cardiolipin synthase 1 stability and mitochondrial function in pneumonia.Cell Rep. 2014 Apr 24;7(2):476-487. doi: 10.1016/j.celrep.2014.02.048. Epub 2014 Apr 3.
• [7] Prevalence and architecture of de novo mutations in developmental disorders. Nature. 2017 Feb 23;542(7642):433-438. doi: 10.1038/nature21062. Epub 2017 Jan 25.
• [8] 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.
• [9] 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.
• [10] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [11] PPARgamma controls CD1d expression by turning on retinoic acid synthesis in developing human dendritic cells. J Exp Med. 2006 Oct 2;203(10):2351-62.
• [12] 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.
• [13] Persistence of epigenomic effects after recovery from repeated treatment with two nephrocarcinogens. Front Genet. 2018 Dec 3;9:558.