Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0F9NFP)

• DOT Name: Cilia- and flagella-associated protein 418 (CFAP418)
• Gene Name: CFAP418
• Related Disease:
  Cone-rod dystrophy 16
  Bardet-biedl syndrome 21
• UniProt ID: CF418_HUMAN
• Pfam ID: PF14996
• Sequence:
  MAEDLDELLDEVESKFCTPDLLRRGMVEQPKGCGGGTHSSDRNQAKAKETLRSTETFKKE
  DDLDSLINEILEEPNLDKKPSKLKSKSSGNTSVRASIEGLGKSCSPVYLGGSSIPCGIGT
  NISWRACDHLRCIACDFLVVSYDDYMWDKSCDYLFFRNNMPEFHKLKAKLIKKKGTRAYA
  CQCSWRTIEEVTDLQTDHQLRWVCGKH
• Function: May be involved in photoreceptor outer segment disk morphogenesis.
• Tissue Specificity: Widely expressed, with highest levels in heart and brain. Also expressed in the retina (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy 16	DISIUGQN	Definitive	Autosomal recessive	[1]
Bardet-biedl syndrome 21	DISSZ8FS	Limited	Autosomal recessive	[2]

3 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 418 (CFAP418).	[3]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Cilia- and flagella-associated protein 418 (CFAP418).	[4]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cilia- and flagella-associated protein 418 (CFAP418).	[5]

References

• [1] Novel C8orf37 Mutations in Patients with Early-onset Retinal Dystrophy, Macular Atrophy, Cataracts, and High Myopia. Ophthalmic Genet. 2016;37(1):68-75. doi: 10.3109/13816810.2014.949380. Epub 2014 Aug 12.
• [2] 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.
• [3] 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.
• [4] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [5] 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.