Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1273MD)

• DOT Name: Cilia- and flagella-associated protein 44 (CFAP44)
• Synonyms: WD repeat-containing protein 52
• Gene Name: CFAP44
• Related Disease:
  Colon cancer
  Colorectal adenocarcinoma
  Colorectal cancer
  Colorectal cancer, susceptibility to, 1
  Colorectal cancer, susceptibility to, 10
  Colorectal cancer, susceptibility to, 12
  Colorectal carcinoma
  Colorectal neoplasm
  Male infertility
  Spermatogenic failure 20
  Obsolete non-syndromic male infertility due to sperm motility disorder
• UniProt ID: CFA44_HUMAN
• PDB ID: 8J07
• Pfam ID: PF00400
• Sequence:
  MKEPDDQDTDGEKSVTSKSDGKKSLRSSKSESRSPVQEDNTFLEDDTDETFTKGEGSYLE
  EDSDEERLEGSLSSFQYGDLQSTTVPQQTPAPAVEEAEEEVKKKISESFFYDYMELASMP
  FVTLDSNIPLDLLTLVHSFGYDCRKRANLQLLDDSIAIYIAGNQLIFLNLKTKEQIYLRS
  SSGEGIGVIGVHPHKTYFTVAEKGSFPDIIIYEYPSLRPYRVLRDGTEKGYAYVDFNYSG
  NLLASVGSNPDYTLTIWNWKEEQPILRTKAFSQEVFKVTFNPDKEEQLTTSGSGHIKFWE
  MAFTFTGLKLQGSLGRFGKTITTDIEGYMELPDGKVLSGSEWGNMLLWEGGLIKVELCRG
  TSKSCHNGPINQIMLYEGEVITVGSDGYVRIWDFETIDTADVIDETGLLEIEPINELQVD
  KNVNLFSMIKMNETGNNFWLAQDANGAIWKLDLSFSNITQDPECLFSFHSGAIEAVAVSP
  LTYLMATTALDCSVRIYDFASKTPLAQMKFKQGGTALVWVPRMVNFTGAQIIVGFEDGVV
  RILELYDPKGLTIFAGRKKILDADIQLKQVFKPHTACVTALAYERDGEILATGSKDQTVF
  FFEVERDYKPIGYINTPGPVCQLMWSPMSHPESTLLIICENGYILEAPLPTIKQEEDDHD
  VVSYEIKDMCIKCFHFSSVKSKILRLIEIEKRERQRELKEKIREERRNKLAAEMGEDGEK
  EFQEEEEEKEEEEEEEEPLPEIFIPSTPSPILCGFYSEPGKFWVSLGGYDSGFLYHCEFP
  PCDESSDFKEQKDEPIDVRYLADTEDNPIQTITFNINKVMMFCGMKNGAIRVYVLNQNDP
  SLTSLVDYWHFNMHDNNYGCIKSIANSFDDRFLVTAGADGNIFVFNIFSEFMLRKDMKAK
  VPSPRFGIETEPIPEDIEDPKAYSIENARRKREHDKLMKEVGEIKARKREQIKALRSEFC
  NLLEMNEKLPKHMQFKRTDFDVDSQIRAEMHRKTAFKIQQVEKELAWEKEKHELGLMKLK
  NRFRDPLESDTIVVHAILSDHKISSYRLVQPSKYSKFKRASQSERKPSKLDRFEKEGPGR
  KDSQRDAGGSVTIQEESIIEKGKKFRPKTLSEIIVENQIEKTRKLILKAERAQLKIQQRK
  KEWEELYKSKPGDDYEDPKDLQAIKEAQVYMGDFNLKTAPDYKIPEHMRINAAKKEEELG
  HLDSLVHGNKRHMNKCILSLRDLKVAVVEEIQCLVQELKNIQSTLHISKHIPIPKIPQIH
  PEEVPEKRFQYDEETLLNFKQQQMKSKDEKSPGVEQTGSGGPVGGFLKLSSRKDGDLTTR
  DSISRSSKASTFSLDIPKCLEFEKAEPTDVELEIMKRDEIKHVYMQQYLVNRIKELVVTF
  DAELRLLRHQKLKLDTQMKLSDLHHVTLFQEILLLKNFEKQENILQERVNSLDKEEQYMQ
  WKINETLKEMEEKKNEITKLQEQEKALYAGFQAAIGENNKFANFLMKVLKKKIKRVKKKE
  VEGDADEDEESEESSEEESSLESDEDESESEDEVFDDSICPTNCDVALFELALHLREKRL
  DIEEALVEEKKIVDNLKKEYDTLSKKVKIVATNLNAAEEALEAYQREKQQRLNELLVVIP
  LKLHQIEYVVFGEIPSDLSGTLVFSNHALRRLQERIHELQEENSKQQKLNKEWRERRKQL
  IREKREMTKTIHKMEETVRQLMISKFGRVVNLEALQTLSVNTTLEELKIRKLRKELANAK
  EMKMWEEKIAQMRWELMMKTKEHTRKLYQMNDLCIEKKKLDSRLNTLQNQQGNAFQGPRE
  ADVVAREEVTELIQLQAERISALKEEIALLRRKGSLILPPIQSPREKEIQPADL
• Function: Flagellar protein involved in sperm flagellum axoneme organization and function.
• Tissue Specificity: Testis-specific.

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Colon cancer	DISVC52G	Strong	Genetic Variation	[1]
Colorectal adenocarcinoma	DISPQOUB	Strong	Genetic Variation	[1]
Colorectal cancer	DISNH7P9	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 1	DISZ794C	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 10	DISQXMYM	Strong	Genetic Variation	[1]
Colorectal cancer, susceptibility to, 12	DIS4FXJX	Strong	Genetic Variation	[1]
Colorectal carcinoma	DIS5PYL0	Strong	Genetic Variation	[1]
Colorectal neoplasm	DISR1UCN	Strong	Genetic Variation	[1]
Male infertility	DISY3YZZ	Strong	Genetic Variation	[2]
Spermatogenic failure 20	DISPF5HX	Moderate	Autosomal recessive	[3]
Obsolete non-syndromic male infertility due to sperm motility disorder	DISG7641	Supportive	Autosomal recessive	[4]

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 44 (CFAP44).	[5]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cilia- and flagella-associated protein 44 (CFAP44).	[12]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[7]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[8]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[10]
Hydroquinone	DM6AVR4	Approved	Hydroquinone decreases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[8]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cilia- and flagella-associated protein 44 (CFAP44).	[13]

References

• [1] Bayesian and frequentist analysis of an Austrian genome-wide association study of colorectal cancer and advanced adenomas.Oncotarget. 2017 Oct 9;8(58):98623-98634. doi: 10.18632/oncotarget.21697. eCollection 2017 Nov 17.
• [2] Mutations in CFAP43 and CFAP44 cause male infertility and flagellum defects in Trypanosoma and human.Nat Commun. 2018 Feb 15;9(1):686. doi: 10.1038/s41467-017-02792-7.
• [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] Biallelic Mutations in CFAP43 and CFAP44 Cause Male Infertility with Multiple Morphological Abnormalities of the Sperm Flagella. Am J Hum Genet. 2017 Jun 1;100(6):854-864. doi: 10.1016/j.ajhg.2017.04.012. Epub 2017 May 25.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [8] 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.
• [9] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [10] The contribution of methotrexate exposure and host factors on transcriptional variance in human liver. Toxicol Sci. 2007 Jun;97(2):582-94.
• [11] Keratinocyte-derived IL-36gama plays a role in hydroquinone-induced chemical leukoderma through inhibition of melanogenesis in human epidermal melanocytes. Arch Toxicol. 2019 Aug;93(8):2307-2320.
• [12] 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.
• [13] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.