Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTTDRT2N)

• DOT Name: Cilia- and flagella-associated protein 298 (CFAP298)
• Synonyms: Protein kurly homolog
• Gene Name: CFAP298
• Related Disease:
  Chronic kidney disease
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia 26
  Primary ciliary dyskinesia
• UniProt ID: CF298_HUMAN
• Pfam ID: PF11069
• Sequence:
  MVLLHVKRGDESQFLLQAPGSTELEELTVQVARVYNGRLKVQRLCSEMEELAEHGIFLPP
  NMQGLTDDQIEELKLKDEWGEKCVPSGGAVFKKDDIGRRNGQAPNEKMKQVLKKTIEEAK
  AIISKKQVEAGVCVTMEMVKDALDQLRGAVMIVYPMGLPPYDPIRMEFENKEDLSGTQAG
  LNVIKEAEAQLWWAAKELRRTKKLSDYVGKNEKTKIIAKIQQRGQGAPAREPIISSEEQK
  QLMLYYHRRQEELKRLEENDDDAYLNSPWADNTALKRHFHGVKDIKWRPR
• Function: Plays a role in motile cilium function, possibly by acting on outer dynein arm assembly. Seems to be important for initiation rather than maintenance of cilium motility. Required for correct positioning of the cilium at the apical cell surface, suggesting an additional role in the planar cell polarity (PCP) pathway. May suppress canonical Wnt signaling activity.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Chronic kidney disease	DISW82R7	Strong	Genetic Variation	[1]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[2]
Primary ciliary dyskinesia 26	DISJNMG2	Moderate	Autosomal recessive	[3]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cilia- and flagella-associated protein 298 (CFAP298).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Cilia- and flagella-associated protein 298 (CFAP298).	[5]
Quercetin	DM3NC4M	Approved	Quercetin decreases the expression of Cilia- and flagella-associated protein 298 (CFAP298).	[6]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Cilia- and flagella-associated protein 298 (CFAP298).	[8]
QUERCITRIN	DM1DH96	Investigative	QUERCITRIN decreases the expression of Cilia- and flagella-associated protein 298 (CFAP298).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the methylation of Cilia- and flagella-associated protein 298 (CFAP298).	[7]

References

• [1] Identification of C21orf59 and ATG2A as novel determinants of renal function-related traits in Japanese by exome-wide association studies.Oncotarget. 2017 Jul 11;8(28):45259-45273. doi: 10.18632/oncotarget.16696.
• [2] Zebrafish Ciliopathy Screen Plus Human Mutational Analysis Identifies C21orf59 and CCDC65 Defects as Causing Primary Ciliary Dyskinesia. Am J Hum Genet. 2013 Oct 3;93(4):672-86. doi: 10.1016/j.ajhg.2013.08.015.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [7] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Molecular mechanisms of quercitrin-induced apoptosis in non-small cell lung cancer. Arch Med Res. 2014 Aug;45(6):445-54.