Details of Drug Off-Target (DOT)

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

• DOT Name: Ciliogenesis and planar polarity effector 1 (CPLANE1)
• Synonyms: Protein JBTS17
• Gene Name: CPLANE1
• Related Disease:
  Joubert syndrome 17
  Orofaciodigital syndrome type 6
  Holoprosencephaly
  Isolated congenital microcephaly
  Joubert syndrome 1
  Orofaciodigital syndrome
  Postaxial polydactyly
  Joubert syndrome
  Allergic asthma
  Cardiac arrest
  Ciliopathy
  Glaucoma/ocular hypertension
  Sickle-cell anaemia
  Vitelliform macular dystrophy
• UniProt ID: CPLN1_HUMAN
• Pfam ID: PF15392
• Sequence:
  MEIRLEILTSTGIKQKKPWPRVSWLGKEKEAVFLLDDKFINEINLLSGKIKKKIPSLQPF
  LKDVIVLTTSSNDAWLAGVLTTGELFLWNKDQDCLKTIPITEKPKEMIKATVASSLRLYL
  YVSGNGKRIVLITPSGCIFLWEYLELKNILSSKSLSLAGRWSQVIPEEAVLLPSTEDKEA
  VVNAVFIKNELFGDCCLCSFTFYSGECLKLTFLAIRWHENVFTSVRSLPYHVHWAQQDCH
  LCSLIPKCESVKSRGALISAFSRDGLTLAVTLNQKDPKATQVLFINTLNFVTLCGSLKGC
  SNKSPVVPATLIRSYWVGDISWTHDSLFLACMLKRGSLVLLTCQGELLTLITFGCSIEFG
  PAEFIPLHPLITYRPQQFTFQDSNNSVDSSASDSDPMRQRFSIKAHSRLPYLVISDGYMV
  TTLRFLDSLSPSVHMRSLLLDSTQRLEKIYQSVILSKPKGKGLNLRSLNSLRSSLLEHQG
  NESSADFTVPKFLQAEETINENAADFQDFEAEETNEGRHFPDNLCPFWNKRDDVLCSSMK
  EGRLEFASMFDTIHAKDDSEETDRTITELHSIQKSLLAAWTIGISKTVTEKNLMLNYIVV
  CITHFFYILQFIKCPFPKLDLVLSKSSRHNAWILCIFQLFHQCLSIHYWDIRYKQDVGHL
  IKLTSNTVKLLLTQQQKGQLFSEKLLACFYLLKMVADNLNGVYILQPEVISASADGSKIT
  AQDSLVVPIFQMFQDSGFQKNWSWNSFFKIHPQVVNPVQQPGHRLLILWRILYKKTLWYQ
  AQLNRRVPEADSQLTEKMTHEASTVKSLLCHLQANLQSTGDCLNQTLELKSINGEECFLL
  GSYEKSVQLWKKALQEIEEKGGRRTYFLQIRYYLSLLYCHLYSYNLNDAQGLCDQLAREI
  LRWSQLPVKENKDFSGAAKSHFECGMVGGVHPEAAVRVVQSMARFMAAYFTNQQLCILPP
  HHVNVLPPLHIKTEQSFRLIPLQHSKVASVVRDQNLSNVWTVEYALELLFIGGLVPEAVW
  LAYKLGDWKTSVSIGVAFQLFCKRDSNFMRSKKKSLNLPLRMTPAQIFQEKLQCVLGQPA
  SLEAKNEMGSKYKQFTDPIEEEDANLLFGSVQEVLKASVMADADILSETFQLLIDSAKDF
  SKRLWGLVPFGLYLPAPPLYCPQPAILSEEDGDDLLLKAEKNNRQKVSGILQRVLLLFRA
  AQCSFPVAQWYILQLRWARKVMQKIRMKGSLPSLSPFPQSLLNYCKGGIAFFRPGAAGDH
  KLDEVSIRAIGCFRELCALCWMLHVRDKLSYSCRQYQKARENVKGEKDLEVEFDSCMIEH
  CLSAVEWAYRMLPFSRFFNMEELIQDIILSLIGELPPIRKVAEIFVKAFPYPEDVRVPLR
  DKYHSLHQRLRHCVVKGPQTEEMMSVVMHSIQKVRVKALKRVQRNIGSFEVNIWEPIEEE
  KPDEAPGVDRYSLGTSLSRSTLTELGDSVVHSDADTFSEALSVEEKSRINIYQRNAPNHM
  ELTSIHKPTDKRKMCNQKENPTKKEDHEKLSQNTLPVIGVWEFERDDDEYIKFLDLFLSY
  ILERDLPYSRDADIPFLTSFSGKLREHELNSLLFDVHTTLKRHQSKTKSQNVFRAGSCFV
  VAPESYESEKSSSLNDEYGMHLENQKLSSSVLVNQGIKPFLQYPSNEVNKNEGMSGLFGL
  KQRSIYKIQDDTREKCLIQRSSNHIFWTPKSIKTRRCIFKAIQCNDINPQEDLPLALNTF
  GSIGRLLEWMIRWSNRRLLCDSGITESSSEYSPVIRVKTSTAAILTSLWLLEQPYFATYK
  AKNAIIKMVENRDTGCQIGPNIERESKSDAGGSVAVATPGGTEERNGQNKSCQNILNRMP
  TEAKNPDIKEINDDIISITHNTKKEFIDIDENLLEVEAFTEEEMDMHISDYEEDIEESVG
  GFRSPSLAICMMTLPQQLEEEFTEEVQCQREEPLETIMEEKSTEQKGMIEAFSHPGHTTP
  QSMQVDTSSEISSAQISTYKEKSSSVPLLISNGVNVASQPPAPTPQKTQRNEFTAQLPDC
  SESVRQMLQDEMFKLVQLQQINFMSLMQIVGSSFANLPDTQQLVQQSQSVHLGESQESNL
  RGCGDVEDSNKNLKERFFIKPQSMGENAREPRKNSPHCHEGTIPSGQNSTGNVQNVPHGS
  IPLCQLNGQPRKKGPIPSSQNLPSTSFYPAPAGNTHLYLLSTPSVVQKAPRLIPHAKTFS
  PGDGFPLLQFKSKQEFQPLFLHTGSIPQVPFRPLPQPREAWGLSDSFQPALPQRAAQTTP
  ASHLNVSQYNTEARKKEVEQKTWAETVITEIPNHVNLDQYVGQENLTPQQDSSVFIKPEK
  LFDVKPGTLEISPHHSFGLPLLYLPLKPPNMFPSTSRASITVPSTPIQPIAEERKYPRLS
  LLHSHLSPENRCKKTQLIPLENLIAFKQSQQKLTHNLFEQGDAGHLQLLKVKIEPPEVRQ
  GKDSKKRQRRRAEKELQEKRCEKLRRKPNVTFRPENSIINNDDSEIIKKPKEQQEHCGSH
  PLDDFDVPFEMLQDDNTSAGLHFMASVKKKAIGSQDASTNTDPEHEPLTAPQLLVPDVYL
  NLKLSSEMSEKPWSPSIPHTVTNLELPVREEPSNDNVIKQQSDHLAVPSSAELHYMAASV
  TNAVPPHNFKSQGLPKPEFRFKGQSTKSDSAEDYLLWKRLQGVSAACPAPSSAAHQLEHL
  SAKLQKIDEQLLAIQNIAENIEQDFPKPEMLDLHCDKIGPVDHIEFSSGPEFKKTLASKT
  ISISEEVRFLTHMDEEDQSDKKETSEPEFSITENYSGQKTCVFPTADSAVSLSSSSDQNT
  TSPGMNSSDELCESVSVHPLQMTGLTDIADIIDDLIIKDGVSSEELGLTEQAMGTSRIQH
  YSGRHSQRTDKERREIQAWMKRKRKERMAKYLNELAEKRGQEHDPFCPRSNPLYMTSREI
  RLRQKMKHEKDRLLLSEHYSRRISQAYGLMNELLSESVQLPTLPQKPLPNKPSPTQSSSC
  QHCPSPRGENQHGHSFLINRPGKVKYMSKPSYIHKRKSFGQPQGSPWPHGTATFTIQKKA
  GGAKAAVRKATQSPVTFQKGSNAPCHSLQHTKKHGSAGLAPQTKQVCVEYEREETVVSPW
  TIPSEIHKILHESHNSLLQDLSPTEEEEPEHPFGVGGVDSVSESTGSILSKLDWNAIEDM
  VASVEDQGLSVHWALDL
• Function: Involved in ciliogenesis. Involved in the establishment of cell polarity required for directional cell migration. Proposed to act in association with the CPLANE (ciliogenesis and planar polarity effectors) complex. Involved in recruitment of peripheral IFT-A proteins to basal bodies.

Molecular Interaction Atlas (MIA) of This DOT

14 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Joubert syndrome 17	DIS9LHZ1	Definitive	Autosomal recessive	[1]
Orofaciodigital syndrome type 6	DISQY7K4	Definitive	Mitochondrial	[2]
Holoprosencephaly	DISR35EC	Strong	Genetic Variation	[3]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[4]
Joubert syndrome 1	DISC9Q82	Strong	GermlineCausalMutation	[5]
Orofaciodigital syndrome	DISSB296	Strong	Genetic Variation	[6]
Postaxial polydactyly	DIS085OV	moderate	Genetic Variation	[7]
Joubert syndrome	DIS7P5CO	Supportive	Autosomal recessive	[5]
Allergic asthma	DISHF0H3	Limited	Genetic Variation	[8]
Cardiac arrest	DIS9DIA4	Limited	Biomarker	[9]
Ciliopathy	DIS10G4I	Limited	Biomarker	[4]
Glaucoma/ocular hypertension	DISLBXBY	Limited	Biomarker	[10]
Sickle-cell anaemia	DIS5YNZB	Limited	Biomarker	[9]
Vitelliform macular dystrophy	DISEFYYN	Limited	Genetic Variation	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[11]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[12]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[13]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[14]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[16]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane decreases the expression of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[17]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Ciliogenesis and planar polarity effector 1 (CPLANE1).	[15]

References

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• [2] C5orf42 is the major gene responsible for OFD syndrome type VI. Hum Genet. 2014 Mar;133(3):367-77. doi: 10.1007/s00439-013-1385-1. Epub 2013 Nov 1.
• [3] Clinical and experimental evidence suggest a link between KIF7 and C5orf42-related ciliopathies through Sonic Hedgehog signaling.Eur J Hum Genet. 2018 Feb;26(2):197-209. doi: 10.1038/s41431-017-0019-9. Epub 2018 Jan 10.
• [4] Extraciliary roles of the ciliopathy protein JBTS17 in mitosis and neurogenesis.Ann Neurol. 2019 Jul;86(1):99-115. doi: 10.1002/ana.25491. Epub 2019 May 3.
• [5] Mutations in C5ORF42 cause Joubert syndrome in the French Canadian population. Am J Hum Genet. 2012 Apr 6;90(4):693-700. doi: 10.1016/j.ajhg.2012.02.011. Epub 2012 Mar 15.
• [6] Beyond the panel: preconception screening in consanguineous couples using the TruSight One "clinical exome".Genet Med. 2019 Mar;21(3):608-612. doi: 10.1038/s41436-018-0082-9. Epub 2018 Jul 2.
• [7] Joubert syndrome: genotyping a Northern European patient cohort.Eur J Hum Genet. 2016 Feb;24(2):214-20. doi: 10.1038/ejhg.2015.84. Epub 2015 Apr 29.
• [8] Human uteroglobin gene: structure, subchromosomal localization, and polymorphism.DNA Cell Biol. 1997 Jan;16(1):73-83. doi: 10.1089/dna.1997.16.73.
• [9] Genetic modifiers of sickle cell anemia in the BABY HUG cohort: influence on laboratory and clinical phenotypes.Am J Hematol. 2013 Jul;88(7):571-6. doi: 10.1002/ajh.23457. Epub 2013 May 30.
• [10] Disease-specific Preference-based Measure of Glaucoma Health States: HUG-5 Psychometric Validation.J Glaucoma. 2019 Jul;28(7):593-600. doi: 10.1097/IJG.0000000000001267.
• [11] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [12] 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.
• [13] 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.
• [14] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [15] 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.
• [16] 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.
• [17] 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.