Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTS62YA2)

• DOT Name: F-box only protein 40 (FBXO40)
• Synonyms: Muscle disease-related protein
• Gene Name: FBXO40
• Related Disease:
  Autism
  Limb-girdle muscular dystrophy
• UniProt ID: FBX40_HUMAN
• Pfam ID: PF15966 ; PF15965
• Sequence:
  MGKARRSPPGHHRHCEGCFNRHCHIPVEPNTSCLVISCHLLCGATFHMCKEAEHQLLCPL
  EQVPCLNSEYGCPLSMSRHKLAKHLQVCPASVVCCSMEWNRWPNVDSETTLHENIMKETP
  SEECLDTALALQDQKVLFRSLKMVELFPETREATEEEPTMNGETSVEEMGGAVGGVDIGL
  VPHGLSATNGEMAELSQEEREVLAKTKEGMDLVKFGQWENIFSKEHAASALTNSSASCES
  KNKNDSEKEQISSGHNMVEGEGAPKKKEPQENQKQQDVRTAMETTGLAPWQDGVLERLKT
  AVDAKDYNMYLVHNGRMLIHFGQMPACTPKERDFVYGKLEAQEVKTVYTFKVPVSYCGKR
  ARLGDAMLSCKPSEHKAVDTSDLGITVEDLPKSDLIKTTLQCALERELKGHVISESRSID
  GLFMDFATQTYNFEPEQFSSGTVLADLTAATPGGLHVELHSECVTRRHNKSSSAFTFTCN
  KFFRRDEFPLHFKNVHTDIQSCLNGWFQHRCPLAYLGCTFVQNHFRPPGQKAKVIYSQEL
  KTFAIKPEVAPELSEGRKNNHLLGHGGKSQNSLTSLPLEILKYIAGFLDSVSLAQLSQVS
  VLMRNICATLLQERGMVLLQWKKKRYSHGGTSWRVHREIWQFSSLFSKIKSWEFNEVTSM
  SEHLKSCPFNIVEHKTDPILLTSMCQPREQARESLVSTFRIRPRGRYVS
• Function: Probable substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex that may function in myogenesis.
• Tissue Specificity: Expressed only in heart and skeletal muscle.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism	DISV4V1Z	Strong	Biomarker	[1]
Limb-girdle muscular dystrophy	DISI9Y1Z	moderate	Altered Expression	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of F-box only protein 40 (FBXO40).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of F-box only protein 40 (FBXO40).	[4]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of F-box only protein 40 (FBXO40).	[5]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of F-box only protein 40 (FBXO40).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of F-box only protein 40 (FBXO40).	[7]
Maleic Acid	DM4L0R7	Investigative	Maleic Acid increases the expression of F-box only protein 40 (FBXO40).	[8]

References

• [1] Autism genome-wide copy number variation reveals ubiquitin and neuronal genes.Nature. 2009 May 28;459(7246):569-73. doi: 10.1038/nature07953. Epub 2009 Apr 28.
• [2] FBXO40, a gene encoding a novel muscle-specific F-box protein, is upregulated in denervation-related muscle atrophy.Gene. 2007 Dec 1;404(1-2):53-60. doi: 10.1016/j.gene.2007.08.020. Epub 2007 Sep 7.
• [3] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [4] 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.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [7] 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.
• [8] Profiling transcriptomes of human SH-SY5Y neuroblastoma cells exposed to maleic acid. PeerJ. 2017 Apr 5;5:e3175.