Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTA7XY4B)

• DOT Name: F-box/WD repeat-containing protein 12 (FBXW12)
• Synonyms: F-box and WD-40 domain-containing protein 12; F-box only protein 35
• Gene Name: FBXW12
• Related Disease:
  Parkinson disease
  Epithelial ovarian cancer
  Neoplasm
• UniProt ID: FBW12_HUMAN
• Pfam ID: PF12937
• Sequence:
  MEIRLPDLALKRIFSFLDLFGLLQVSQVNKHWNRIADSDYLWRSLSLQRWDCSNFTNQHL
  GTHTWKQFFLHQRRKELRLALAQPHNFIYKVTKNIAFETELAYLSGNRLTVDEQEKSIIC
  SVSPKQELCAWDVQEGTMIWSSPVQEFHFSNLVTLPQMHLAITMDRKKTIKVWNCQDRDA
  LAVLPMPQPCYCMEAYLTKDGPFLMVGDAAGDIYTFTLPGLRDVSKVTAFQYGIVLLHCS
  PDKKWVFACGTYSRTLPQVFLTESLLRPSEGSVPLSTFLPHKLCASACWTPKVKNRITLM
  SQSSTGKKTEFITFDLTTKKTGGQTVIQAYEIASFQVAAHLKCPIWMGASDGYMIVFTSG
  PYLLLFSITGFLLQRFEDHQAAINNFWVDPCYVLTTSENSVHVYMWEEGGRHPYLRSCCH
  LENTWHDHTTDSCISSVMCDNASIVLRVRKVSDSSILVMYSLNT
• Function: Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex. Promotes degradation of interleukin-22 receptor subunit IL22RA1 in resting and IL22-stimulated conditions by facilitating its ubiquitination. Functions as a cell growth suppressor.
• Tissue Specificity: Ubiquitously expressed.
• Reactome Pathway:
  Antigen processing (R-HSA-983168)
  Neddylation (R-HSA-8951664)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Parkinson disease	DISQVHKL	Definitive	Genetic Variation	[1]
Epithelial ovarian cancer	DIS56MH2	Strong	Biomarker	[2]
Neoplasm	DISZKGEW	Strong	Genetic Variation	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of F-box/WD repeat-containing protein 12 (FBXW12).	[3]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of F-box/WD repeat-containing protein 12 (FBXW12).	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of F-box/WD repeat-containing protein 12 (FBXW12).	[5]
D-glucose	DMMG2TO	Investigative	D-glucose increases the expression of F-box/WD repeat-containing protein 12 (FBXW12).	[6]

References

• [1] Genetic Analysis of FBXO2, FBXO6, FBXO12, and FBXO41 Variants in Han Chinese Patients with Sporadic Parkinson's Disease.Neurosci Bull. 2017 Oct;33(5):510-514. doi: 10.1007/s12264-017-0122-5. Epub 2017 Mar 24.
• [2] FBXW12, a novel F box protein-encoding gene, is deleted or methylated in some cases of epithelial ovarian cancer.Int J Clin Exp Pathol. 2015 Sep 1;8(9):10192-203. eCollection 2015.
• [3] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [4] 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.
• [5] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [6] Circ_0123996 promotes the proliferation, inflammation, and fibrosis of mesangial cells by sponging miR-203a-3p to upregulate SOX6 in diabetic nephropathy. J Biochem Mol Toxicol. 2022 Nov;36(11):e23139. doi: 10.1002/jbt.23139. Epub 2022 Sep 8.