Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTRZZHB9)

• DOT Name: Cilia- and flagella-associated protein 46 (CFAP46)
• Synonyms: Tetratricopeptide repeat protein 40
• Gene Name: CFAP46
• Related Disease: Nasopharyngeal carcinoma
• UniProt ID: CFA46_HUMAN
• Pfam ID: PF03568
• Sequence:
  MDLVITQELARAESQQDAASLKKAYELIKSANLGKSEFDPSESFSPDLFVLCAEQALKMR
  QPEVSEDCIQMYFKVKAPITQFLGRAHLCRAQMCAPKSAENLEEFENCVTEYMKAINFAK
  GEPRYYFLVYNASVLYWQMVRPFLKPGYRHHLIPSLSQIINVLSQTEEEDKEWRAELMLE
  LLECYLQAGRKEEAARFCSTAAPFIKSHVPQKYRQIFSVMVRHELMDELQLKEEKKNSIS
  LSVTFYINMLKAKAEQNDLPGDISVILRKAYRHLGHYNHQRFPSISEEKMLLLFELARFS
  LTLKCMEISSACLSDLKKMESKDPGKLIEMECLECESEALRLESKMKVYNRAAVEAQLDI
  IQRLDVALQRAVRLGDPRVIHVVCATQWNTCLPLLQHNLRHHLRKPLAGVADVLEKLDSL
  MTLLRCQVHMEMAQIEEDEDRLEPATEHLRKAARLDSLGLYRDRIQMASTRLRLCTTLYQ
  APERAEDKAIMAVEQAKKATPKDSVRKKRALLVNAGLALAPDAFQIVLDSENEAKVSTGK
  NRGRFTYLCAKAWHHTVSVDKAAGHLRRLGNENDKERIQIWAELAKVARKQGVWDVCRTA
  SRFCLLYDNVKVKKLRLRRGKKKRGRDGSVQDTWSQPEVVLQRQVCPDLLRKFAEVGFIH
  AEATVHLLRSEGVELNDRAIPPEDLSQHPAGYVPEPPEVNAEWITYRTWIESLSRCAMNN
  WLRSAEIGQEIQEAWIVQNAVVYVLNHNHHLILAGRQKELVDALYHLLSIVKATGHSGDP
  VMLVTLCNTLARGLIISWIPVQAAEKSRKFMRPNAFHSPLDAGATSEIKTAVEVCEFALN
  LTNGSAPEETVPTGTRQQLIATWVKAKQLLQQQIGPRLGTEEQGTNEDVSSVTRVLVALE
  MYSCNGLGLMDFTVPSLAQLVKMASECNWSDPLVELQTLTRLTHFAHAARDHETTMACAH
  RALEMGIKYLKKFGPEESRLVAEMLCTATAIQGRSIMENLKGRKQLRLVAAKAFTESARF
  GGIAGSSALVMLAARHYWNAWLPLLSSAVYRKKAKGALKRLIGIINKTEARKQEKGKTLL
  LHQWPTADFQGGGTTEGYFLPGAEDDLALRAALYGLLFHSHADQDDWEGGLKVLDEAVQV
  LPRTAHRLLIFKHMVIVKAKLGQNFSMEIQKFKAESEDYLARMWHRLALNSPSVSGELAC
  YNNAIQALQKPEMEWQKVEYLMEFGQWLHHRHFPLEDVVFHLRWAVEILLAMKPPGDVPE
  PQPTPDGEYVAVEMPPRSPVSEAEEAVSLEQLRSVRQLEALARVHILLALVLSPGAEGYE
  DCCLAAYAFFRHIWQVSLMTAGKSVLENRPLAATSSHLLLPKKEKENERSKEKEKERSKE
  KENERSKEKDKEKGKEEKVKEPKQSQSPAPIKQLEDLPMSIEEWASYSCPEEVLSVLKQD
  RSDSTVNPSSIQKPTYSLYFLDHLVKALQKMCLHELTVPVLQLGVLISDSVVGSKGLSDL
  YHLRLAHACSELKLREAAARHEEAVGQVCVSELEQASCRKEIALKKEKNKEPLLEESLPA
  LNEQTLPVQPGEIKPLDAKDKILKMNGETGRDLDGTSFPHLWMLKAEVLLEMNLYQPARL
  LLSEAYLAFQELDEPCAEAQCLLLLAQLANKEKNYGQAKKMIAQAQHLGGSEEFWYNSTL
  TLAEALLSMEHSGREATVCHIFQKLINAFKILKKERPNRLPLLEFMITDLEARCLSLRVR
  VAQHSAVTEPTECSLLLKEMDDGLLEIERKFIDCGCKENCVDVKLERAKIKRLRAQNEKD
  EEQKTAYYLEAYGLAQGAVAEEEGRLHSIQGLYGLAQGAMAEEEGRLHSVQGLLSLQDLQ
  NVNTPLMRKLARLKLGLVEMALDMLQFIWEEAHGQQSEQGSLEKLLADYLQNTSDYTSVG
  LQWFTLKRTLAHGALAQLGSLQPLSVGCVEIRARLLGLAGRALHLLAMQADPVHPTCYWE
  AGPSVGAKLSGLKSLELEVEEEGATKSSRDPPASRAAPEEHCRRGEDLKRRMVLAQQYLA
  QASEVLLQCLQVALGSGLLDVAAAASLEMVECVGTLDPATTCQFLALSQSCSASETMRDV
  LLAATANTSSSQLAALLQLQHQLRCQDRTTTSLGARVEQRLAAVSKAWQNLCVTEQHFNL
  LNEMPPTFWILFLHLSGDRSRLYGAAYEKPKFITAAKGKVQAVGGSCKVMRLAISPTAFS
  HLLACAQQFRKQTQAQVYSEDMALNIGSEPEGLQVEEKERPVQRLSSVLGPLEELLQPLF
  PLLSLSKARVQTPAVVADSGKSKGKDKERKTSTGQHSTVQPEVADKIVLVADRHLLELPL
  EGLSVFDEGTISSVSREFSLQMLWNRLHKEETEGGVKKEGRSRDPKKRSLAKKGRKGSIP
  RTIPPDCIIVDSDNFKFVVDPYEEAQGPEMLTPVSITQDILERFQDTFTSRWAGHLGSKH
  FPSQAQWEQALGSCSGFFFYGMESFLSHILVERLVAMNLQECQVAVLLDLARSYQSLKRH
  MESVEHRRSVGRWEANWRNSASPSEDEWRRGGEPRRGFSDLEGQAAAAPKLRAPSHHAQL
  GPVWAAAPSHRVVQAWTCLPSAAGAPALASALGSAPLPTHPHLPAPIPSSQLALPFLGLS
  PALGAASARDPPPATSRKAAAWTSSSACLCAPWGLRRGWSCVSSRGQDKGGLPLAALVLS
  CLDQKTIQTVSLFLI
• Function: As part of the central apparatus of the cilium axoneme plays a role in cilium movement.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nasopharyngeal carcinoma	DISAOTQ0	moderate	Posttranslational Modification	[1]

3 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 46 (CFAP46).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cilia- and flagella-associated protein 46 (CFAP46).	[6]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of Cilia- and flagella-associated protein 46 (CFAP46).	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cilia- and flagella-associated protein 46 (CFAP46).	[3]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Cilia- and flagella-associated protein 46 (CFAP46).	[4]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cilia- and flagella-associated protein 46 (CFAP46).	[5]

References

• [1] Identification of a novel methylated gene in nasopharyngeal carcinoma: TTC40.Biomed Res Int. 2014;2014:691742. doi: 10.1155/2014/691742. Epub 2014 Jun 30.
• [2] 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.
• [3] 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.
• [4] The exosome-like vesicles derived from androgen exposed-prostate stromal cells promote epithelial cells proliferation and epithelial-mesenchymal transition. Toxicol Appl Pharmacol. 2021 Jan 15;411:115384. doi: 10.1016/j.taap.2020.115384. Epub 2020 Dec 25.
• [5] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [6] 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.
• [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.