Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTMFT2I9)

• DOT Name: Protein moonraker (KIAA0753)
• Synonyms: MNR; OFD1- and FOPNL-interacting protein
• Gene Name: KIAA0753
• Related Disease:
  Ataxia-telangiectasia
  Ciliopathy
  Neoplasm
  Orofaciodigital syndrome
  Orofaciodigital syndrome I
  Orofaciodigital syndrome XV
  Osteochondrodysplasia
  Skeletal dysplasia
  Orofaciodigital syndrome type 6
  Jeune syndrome
• UniProt ID: MOONR_HUMAN
• Pfam ID: PF15718
• Sequence:
  MGPGQPASTCVHLAPRTQLDGRSDPKVLQTQNQLQFNRNVPTHSSNLAIRYSCPHAIRIE
  KLKHSYNESYHCKDADCRVGPDLGSSVSFSVISQERLSYAVHLARRDVKRRQFEKHIKEH
  HLRSQPQSSQKCGHTKYKIPDHRVERKESKSQAACQCSHQPSKVEISSSGAKVYLYSSHP
  GQSDLTVPNSPPTHDPGLQPHPRIGDHKNISEQKSLLEVQRLQKELSSCIHKIEEVTKKD
  RLEEALDPDEERRIRIRRQEQAARSARMLYVLQQQVKEIQEELDKLSPHKIKHTKKSWAM
  SKLAAAHRGAIRALQMFVTQFTDRGEHPLPARCKELGSLIRQLSLCSVKLDADPSVPDVV
  IDILQQIEALESLLEKKLSPKKVKKCFSEIRSRFPIGSQKALERWPSTSPKGERRPLTAK
  DTFPQETSRPSVAKQLLADKYQPDTELPETQRLQSELDVLDADIVLEEGPFILDQSASFK
  DEVLAVAKTKAGKKKPVTENVPFRKKDTLAPARQQGLRKAERGRQSQPHSKSRVQQTTVS
  SRLKMNRQPVKDRKAPWIPPNPTSPPASPKCAAWLKVKTSPRDATKEPLQQEDPQEESHL
  TGAVEHEAARLAWLDAETSKRLKELEELKAKEIDSMQKQRLDWLDAETSRRTKELNELKA
  EEMYRLQQLSVSATHLADKVEEAVLDRLKPLLVKAQRVNSTTEANIHLKDGSSVNTAKAQ
  PAQEVAAVDFESNNIRQLDDFLEDCASELWAVTHAKILGSETLATVEDSKDSPDLEIMMR
  RMEEMEKYQESVRQRYNKIAYADPRLWMQEENNDQKISAISEKPLSPHPIRITKTVDRKD
  PAVNIMLERPCNGNSLDESVGTEEGSEKREAPLLSLAEDSQQKEGRAPLFVPPGMQHSIG
  DYCSRFEQYLRIISHEAVGSFNPWLIAESFSEELVDEALGAVAAELQDMCEDYAEAVFTS
  EFLEAAT
• Function: Involved in centriole duplication. Positively regulates CEP63 centrosomal localization. Required for WDR62 centrosomal localization and promotes the centrosomal localization of CDK2. May play a role in cilium assembly.

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ataxia-telangiectasia	DISP3EVR	Strong	Genetic Variation	[1]
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[2]
Neoplasm	DISZKGEW	Strong	Biomarker	[3]
Orofaciodigital syndrome	DISSB296	Strong	Genetic Variation	[4]
Orofaciodigital syndrome I	DIST27XL	Strong	Genetic Variation	[4]
Orofaciodigital syndrome XV	DISFHVHU	Strong	Autosomal recessive	[5]
Osteochondrodysplasia	DIS9SPWW	Strong	Genetic Variation	[2]
Skeletal dysplasia	DIS5Z8U6	Strong	Genetic Variation	[2]
Orofaciodigital syndrome type 6	DISQY7K4	Supportive	Autosomal recessive	[4]
Jeune syndrome	DISLC357	Limited	Autosomal recessive	[1]

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 Protein moonraker (KIAA0753).	[6]
PMID28870136-Compound-52	DMFDERP	Patented	PMID28870136-Compound-52 increases the phosphorylation of Protein moonraker (KIAA0753).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Protein moonraker (KIAA0753).	[7]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Protein moonraker (KIAA0753).	[8]
Genistein	DM0JETC	Phase 2/3	Genistein increases the expression of Protein moonraker (KIAA0753).	[9]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Protein moonraker (KIAA0753).	[10]
GALLICACID	DM6Y3A0	Investigative	GALLICACID decreases the expression of Protein moonraker (KIAA0753).	[12]

References

• [1] A new case of KIAA0753-related variant of Jeune asphyxiating thoracic dystrophy. Eur J Med Genet. 2020 Apr;63(4):103823. doi: 10.1016/j.ejmg.2019.103823. Epub 2019 Dec 7.
• [2] Novel KIAA0753 mutations extend the phenotype of skeletal ciliopathies.Sci Rep. 2017 Nov 14;7(1):15585. doi: 10.1038/s41598-017-15442-1.
• [3] The Prognostic Value of Lymphovascular Invasion in Truncal and Extremity Soft Tissue Sarcomas: An Analysis from the National Cancer Database.Ann Surg Oncol. 2019 Dec;26(13):4723-4729. doi: 10.1245/s10434-019-07805-x. Epub 2019 Sep 9.
• [4] OFIP/KIAA0753 forms a complex with OFD1 and FOR20 at pericentriolar satellites and centrosomes and is mutated in one individual with oral-facial-digital syndrome. Hum Mol Genet. 2016 Feb 1;25(3):497-513. doi: 10.1093/hmg/ddv488. Epub 2015 Dec 7.
• [5] 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.
• [6] 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.
• [7] 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.
• [8] 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.
• [9] Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein. Mol Cell Proteomics. 2011 Jan;10(1):M110.002170.
• [10] Synergistic effect of JQ1 and rapamycin for treatment of human osteosarcoma. Int J Cancer. 2015 May 1;136(9):2055-64.
• [11] Quantitative phosphoproteomics reveal cellular responses from caffeine, coumarin and quercetin in treated HepG2 cells. Toxicol Appl Pharmacol. 2022 Aug 15;449:116110. doi: 10.1016/j.taap.2022.116110. Epub 2022 Jun 7.
• [12] Gene expression profile analysis of gallic acid-induced cell death process. Sci Rep. 2021 Aug 18;11(1):16743. doi: 10.1038/s41598-021-96174-1.