Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKB5HWT)

• DOT Name: Cilia- and flagella-associated protein 47 (CFAP47)
• Gene Name: CFAP47
• Related Disease: Spermatogenic failure, X-linked, 3
• UniProt ID: CFA47_HUMAN
• Sequence:
  MNTQKGSLTINVHRGSLAMSIQRGSLVPRDMDSSGRDMQLRVIPAEVKFLDTMAGRVYRL
  PITVHNICRWNQKIRFKEPVKPQFKLMLTSLDKELASGLQMTAMVEYHPDKDEDTFDRLL
  ISIENKTTEIPLIGLIPSCQLEIESVVNFGTLVANSKVYSKEITITNHGKAPGIFKAEYH
  GQLPILIFPTSGIVDAKSSMVIKVDFCADQPRIVDEEAIVILQGQPEMLLSIKAHVVEQI
  IELLSMSSDRRLECIHFGPVFFGSSKIKHARVYNNSPEPINWVAIIQDDAVGEELGTDIQ
  QRTDIALNNLTYIRKIKNIDTTIIISCLPNEGTLQPYQKTVITFCFTPKLMAVGKKDIGP
  SYRQDYALFLRFESVGSKDGFLRDDDYKTIKSERFQKVELALTGTGLPVLLQFDPGPVLN
  FKPCFMGERSEIQCIIKNQCELLPVTYHFKKTANFEIDPEKGKITGGGMVDVMCSFVPHQ
  LGVFKVKQMIEIIGLVAEEDLQSLSVKSFHHVYLAFNSICKASTKKVVMKFDPGILPSIR
  NPTGKFVVKDLAKRKNYAPVAMLQSAMTRTHNHRSCEEPVKDMLLAFPNDRAATIRSKDH
  HKHFRPIFTKVPRFNYVNHDFAYTTFEKQQKKLHENYYAMYLKYLRSVRLQKKQAERERM
  YSYDDTDIGLEPGSGLKSPSLSEAEIEEELSSAANSIRANRLLTTRGIASQEEESVRRKV
  LKGLKSEPSTPQEKHDCSLMLTPKQIHQVIVGPSVLNFGNICVNSPNTHLLHVINMLPMH
  VLLQLDTDLEELQKTNQFSYVILPTSSTYISMVFDSPTIGKFWKSFTFTVNNVPSGHILV
  VAVVQPVTLELSSNELVLRPRGFFMKTCFRGTVRLYNRQNCCAQFQWQPVNTGRGIAFSI
  CPAKGTVEAYSSLECEVTWQQGFSSPEEGEFILHVFQGNALKLKCVAHLGRTKVLLLQPR
  ILFSNCPQGLTTWRKAILQNVGQNHAYFKVCSQSLLPIINIIPSQGIVPFGGITVLNISC
  KPTVAEKFDTRAKVSIRHANVIDLRIGGSAEIADVEINPDVFNFSGAYIGGTQIIPFVIK
  NKGITRARVEFNLKDFPDFSMDLKDKSEEFKDPAVPYIYSLELEENTSLECSITFSPKEV
  TVVEFIIQVQINFFESSKLYTKYLSSSPSNPKTVPLIRPCYVQATALQSPLNLSSTKFVF
  EIPLHEMNPNNKVTKTQNLVLYNITKHHVTWTLDLSNTGKLFKDGTFKFSVLNGILRPNE
  KYNVSISFCPNRPGTYTADIPMLLNYIPVCYKILHLTGEVKSPELLFDPPFIFFTPVPLD
  ITTVMDINILPQNYFRNSTLCVQIPTVRLLDGEEIHPLSVKFPKGRVIPGSHSGINNKLT
  CHLSFKSSKPVSFFTNLLFCDDRKNWFSLPVTATAENCILTIYPYMAIHLDKQNIILKND
  KDEYLKKTRDGVLPPYQDAKPPSPASIKKTYTTSKFNDAEPAKGNLFIGVEVLPENLHLD
  ESETSEEDHGSLEKEKYEQFLSLEEGTKAHYFFEKVVNAAQTWFSLFGWPEGPHSFSIPE
  TIRRDVYKMQFYSSTSPPQKFSRQNDFSKYNKTIYDVLLHLSGKMPPGINSSQSLPVDNH
  EKRVIQLHLQHSSLLDFLNAQGGCISHVLPEFLLEPEDYKRWIEIMSSTNTMPVSSCTPK
  KKCSIVIEMSKFEAWSKRAWTDVFLQIYKVLVLSRVVPYCSNNMPPICVQNTPKVNPCFA
  SSNIYSDSERILLSWMNINYENTRHVIWKNCHKDVIPSERWIVNFDKDLSDGLVFATQLG
  AYCPFLIESHFINMYTRPKSPEEYLHNCLIIVNTLYEIDFDVEIQATDICDPNPILMLML
  CVYMYERLPTYLPKKVVSFECTLHDTVLNKILLKNSSSRNLVYNARIVGRDAADFSLSQK
  GNVVTISPRNEINVTLKFTSRFIRPAEASLLLISKPKNAVRGITMTFALKGKVLDFKAID
  IIKCESPCYQFQEVTVNVKNPFHTAGDFSVILVESSTFVSSPTKLTESRQYPKHDDDMSS
  SGSDTDQGCSDSPNVLHTSIKSTFIREFFCSMHTVHLGVKGTSSLELRFLPFNMHVRYCV
  IILSNKKIGQLIYVAEGKGMTPLPSSCLPMNTSSSPVYYSTTREEGPNKKYPVLYLKCKP
  YQILYVDLKLPMTNEAKEKALAFAAQQQMSSIEYERRLITGTLESSSIRVAIALLGLTKI
  ETLMLFRISKLRKPKTVSYTTEVSLPKYFYIPEKISIPWIPEPQVIKLSKAKASDGSVPL
  PLQFLPLQSGRYPCKILLKSRYDVRAYYVEGIVNEEQPEAKFEFETPAFEALTQNIPIKN
  QTNDKWTFQVTIEGEWFYGPVDLHVGPDEIVEYPLTFKPIFECVITGKLILQNEVDGREH
  IFDIKGVGKKPSALEHITVECQVGNVTQKHITLPHFTNTALTFKVTADLPIVWGNPQITV
  YPYKEILYLIHVRPWKRGILKGTITFSTTRRCTTRRKHDDYEEDTDQDQALSCLDSITEQ
  SSILDDADTYGNFNNLRFWYNLEIHSTPGPPIEIMEMTCIALDSTCIEIPLSNPKDRGLH
  LEVQLTSAALNGDNEIILSPLQCTKYIVWYSPATTGYSDESIIFQPEMAEEFWYLLKLTI
  ELPKPTTMPEIQCDLGKHVTQIIPLVNCTHETLKLQVTNSNPENFVLDINRKSQLIISPH
  STTELPVLFYPSALGRADHQACINFYCTQFTEWKFYLSGVGLFPQPLDTERITTRIGLQS
  TIVIPFKNPTMEDVLIDIILTSVEHPRNLVMDHCWDSFIYESSAFRFSSPSEIQGIALPP
  KGNIDISLLFIPQIMKLHKTMVIIEMTKANGKYWPIDNFDELDIKFKSIVGIDSEEIQAI
  HWIYPIVGLPQAPPPKSPPVVIQCQSRKRAEEKVEIILNAGFFGFSLTPDLTEVLVIPKR
  NSHNFCEDPNEIPKIHEFEYEIQFESEAMKSKLESCVALYMIEKSYDIMAKRITFIFNLV
  FTPKKPLRSHITLKIECVTEGIWKFPIMLIATEPDTDAVIDIEGVGLFKESVFELRLKSQ
  TRNPEPFTAHFLPGSDLEFFVKPQAGELLPFNTNGTLITVGFKPKMYCRKYKATLVIQTE
  EMYWKYEINGLTPTTVPPKNAKAKIDATHKTHDNMPVRPHNFVRENTKLIRTGVSSTIKG
  APLVKNQ
• Function: Plays a role in flagellar formation and sperm motility.
• Tissue Specificity: Highly expressed in spermatzoa (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spermatogenic failure, X-linked, 3	DISNVHUB	Limited	X-linked	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Cilia- and flagella-associated protein 47 (CFAP47).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the methylation of Cilia- and flagella-associated protein 47 (CFAP47).	[6]

3 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 47 (CFAP47).	[3]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Cilia- and flagella-associated protein 47 (CFAP47).	[4]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Cilia- and flagella-associated protein 47 (CFAP47).	[5]

References

• [1] 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.
• [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] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [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.