Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0GKNAU)

• DOT Name: Cilia- and flagella-associated protein 251 (CFAP251)
• Synonyms: WD repeat-containing protein 66
• Gene Name: CFAP251
• Related Disease:
  Spermatogenic failure 33
  Obsolete non-syndromic male infertility due to sperm motility disorder
• UniProt ID: CF251_HUMAN
• PDB ID: 8J07
• Pfam ID: PF00400
• Sequence:
  MSDAAEAPREATGENGETEMKEEEEPNPNYKEVEDPQQESKDDTIAWRESQEEERKTGEE
  EGEEEGKEDKKIVMEETEEKAGEVQEKEASGIQEETTVEPQEVTASMIRLETQITDSQSI
  TSGIFPKTQRGSKSKLSLQLEDAETDELLRDLSTQIEFLDLDQISPEEQQISSPERQPSG
  ELEEKTDRMPQDELGQERRDLEPENREEGQERRVSDIQSKAGISRESLVSSTTEDILFQK
  DKSTPVYPLTMTWSFGWNSSLPVYYIREERQRVLLYVCAHTAIIYNVFRNNQYHLQGHAN
  IISCLCVSEDRRWIATADKGPDCLVIIWDSFTGIPVHTIFDSCPEGNGIMAMAMTHDAKY
  LATISDAEVQKVCIWKWTLAVETPACTLELPTEYGVQNYVTFNPTNNKELVSNSKTRAIY
  YAWYEERDTLAHSAPLLTEKTFNKLVGKFSQSIFHLNLTQILSATMEGKLVVWDIHRPPS
  SASTFLGFPYIKPCKLVHLQKEGITVLTTIDSYIVTGDIKGNIKFYDHTLSIVNWYSHLK
  LGAIRTLSFSKTPATPPTEKSNYPPDCTLKGDLFVLRNFIIGTSDAAVYHLTTDGTKLEK
  LFVEPKDAICAISCHPYQPLIAIGSICGMIKVWNYENKQYLFSRVFEKGLGVQSLTYNPE
  GALLGAGFTEGTVYILDAMSLENESPEPFKYSRTSVTHISFSHDSQYMATADRSFTVAVY
  MLVVRNGQRVWEYLARLRSHRKSIRSLLFGVYLDSNEPRLLSLGTDRLLIEYDLLRSYKD
  HLEVLDIHHTDQGCYPTCMVWYPPLTRELFLLICNSGYKVKLFNATTKMCRKTLLGPAYG
  SPIEQTQVLPVRSMAELQKRYLVFINRDKVGLQILPVDGNPHKTSAIVCHPNGVAGMAVS
  YDGCYAFTAGGHDRSVVQWKITLSVLEAAVSLGGEDLTPFYGLLSGGREGKFYRELEDYF
  YYSQLRSQGIDTMETRKVSEHICLSELPFVMRAIGFYPSEEKIDDIFNEIKFGEYVDTGK
  LIDKINLPDFLKVYLNHKPPFGNTMSGIHKSFEVLGYTNSKGKKAIRREDFLRLLVTKGE
  HMTEEEMLDCFASLFGLNPEGWKSEPATCSVKGSEICLEEELPDEITAEIFATEILGLTI
  SEDSGQDGQ
• Function: Involved in spermatozoa motility. May also regulate cilium motility through its role in the assembly of the axonemal radial spokes.
• Tissue Specificity: Isoform 1 is highly expressed in testis and, at lower levels, in lung. Very low levels are detected in kidney and brain . In testis, expressed in spermatozoa (at protein level) . Isoform 2 is not detected in testis, lung, kidney, nor in brain .

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spermatogenic failure 33	DISLE1RM	Strong	Autosomal recessive	[1]
Obsolete non-syndromic male infertility due to sperm motility disorder	DISG7641	Supportive	Autosomal recessive	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[2]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[4]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[5]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[6]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[7]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[9]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Cilia- and flagella-associated protein 251 (CFAP251).	[10]

References

• [1] A Homozygous Ancestral SVA-Insertion-Mediated Deletion in WDR66 Induces Multiple Morphological Abnormalities of the Sperm Flagellum and Male Infertility. Am J Hum Genet. 2018 Sep 6;103(3):400-412. doi: 10.1016/j.ajhg.2018.07.014. Epub 2018 Aug 16.
• [2] Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther. 2016 Apr;99(4):432-41.
• [3] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [4] 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.
• [5] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [6] 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.
• [7] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [8] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [9] 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.
• [10] Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.