Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTSSXF56)

• DOT Name: Cilia- and flagella-associated protein 52 (CFAP52)
• Synonyms: WD repeat-containing protein 16; WD40-repeat protein up-regulated in HCC
• Gene Name: CFAP52
• Related Disease:
  Hepatocellular carcinoma
  Hydrocephalus
  Situs inversus
  Visceral heterotaxy
• UniProt ID: CFA52_HUMAN
• PDB ID: 7UNG; 8J07
• Pfam ID: PF00400
• Sequence:
  MDNKISPEAQVAELELDAVIGFNGHVPTGLKCHPDQEHMIYPLGCTVLIQAINTKEQNFL
  QGHGNNVSCLAISRSGEYIASGQVTFMGFKADIILWDYKNRELLARLSLHKGKIEALAFS
  PNDLYLVSLGGPDDGSVVVWSIAKRDAICGSPAAGLNVGNATNVIFSRCRDEMFMTAGNG
  TIRVWELDLPNRKIWPTECQTGQLKRIVMSIGVDDDDSFFYLGTTTGDILKMNPRTKLLT
  DVGPAKDKFSLGVSAIRCLKMGGLLVGSGAGLLVFCKSPGYKPIKKIQLQGGITSITLRG
  EGHQFLVGTEESHIYRVSFTDFKETLIATCHFDAVEDIVFPFGTAELFATCAKKDIRVWH
  TSSNRELLRITVPNMTCHGIDFMRDGKSIISAWNDGKIRAFAPETGRLMYVINNAHRIGV
  TAIATTSDCKRVISGGGEGEVRVWQIGCQTQKLEEALKEHKSSVSCIRVKRNNEECVTAS
  TDGTCIIWDLVRLRRNQMILANTLFQCVCYHPEEFQIITSGTDRKIAYWEVFDGTVIREL
  EGSLSGSINGMDITQEGVHFVTGGNDHLVKVWDYNEGEVTHVGVGHSGNITRIRISPGNQ
  YIVSVSADGAILRWKYPYTS
• Function: Microtubule inner protein (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme. Important for proper ciliary and flagellar beating. May act in cooperation with CFAP45 and axonemal dynein subunit DNAH11. May play a role in cell growth and/or survival.
• Tissue Specificity: Expressed in respiratory cells and sperm (at protein level) . Highly expressed in testis . Up-regulated in hepatocellular carcinoma (HCC) .

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Hepatocellular carcinoma	DIS0J828	Strong	Altered Expression	[1]
Hydrocephalus	DISIZUF7	Strong	Biomarker	[2]
Situs inversus	DISFA7AJ	Supportive	Autosomal dominant	[2]
Visceral heterotaxy	DIS1DV90	Limited	Autosomal recessive	[3]

2 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 Cilia- and flagella-associated protein 52 (CFAP52).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cilia- and flagella-associated protein 52 (CFAP52).	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cilia- and flagella-associated protein 52 (CFAP52).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cilia- and flagella-associated protein 52 (CFAP52).	[6]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cilia- and flagella-associated protein 52 (CFAP52).	[7]

References

• [1] WDRPUH, a novel WD-repeat-containing protein, is highly expressed in human hepatocellular carcinoma and involved in cell proliferation.Neoplasia. 2005 Apr;7(4):348-55. doi: 10.1593/neo.04544.
• [2] A human laterality disorder associated with a homozygous WDR16 deletion. Eur J Hum Genet. 2015 Sep;23(9):1262-5. doi: 10.1038/ejhg.2014.265. Epub 2014 Dec 3.
• [3] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [7] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [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.