Details of Drug Off-Target (DOT)

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

• DOT Name: Cilia- and flagella-associated protein 300 (CFAP300)
• Gene Name: CFAP300
• Related Disease:
  Ciliary dyskinesia, primary, 38
  Primary ciliary dyskinesia 1
  Primary ciliary dyskinesia
• UniProt ID: CF300_HUMAN
• Pfam ID: PF14926
• Sequence:
  MATGELGDLGGYYFRFLPQKTFQSLSSKEITSRLRQWSMLGRIKAQAFGFDQTFQSYRKD
  DFVMAFFKDPNVIPNLKLLSDSSGQWIILGTEVKKIEAINVPCTQLSMSFFHRLYDEDIV
  RDSGHIVKCLDSFCDPFLISDELRRVLLVEDSEKYEIFSQPDREEFLFCLFKHLCLGGAL
  CQYEDVISPYLETTKLIYKDLVSVRKNPQTKKIQITSSVFKVSAYDSAGMCYPSAKNHEQ
  TFSYFIVDPIRRHLHVLYHCYGVGDMS
• Function: Cilium- and flagellum-specific protein that plays a role in axonemal structure organization and motility. May play a role in outer and inner dynein arm assembly.
• Tissue Specificity: Expressed in nasal epithelial cells.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliary dyskinesia, primary, 38	DISHCL8F	Definitive	Autosomal recessive	[1]
Primary ciliary dyskinesia 1	DISPGX6H	Strong	GermlineCausalMutation	[2]
Primary ciliary dyskinesia	DISOBC7V	Supportive	Autosomal dominant	[2]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Cilia- and flagella-associated protein 300 (CFAP300).	[3]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Cilia- and flagella-associated protein 300 (CFAP300).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Cilia- and flagella-associated protein 300 (CFAP300).	[6]
Cannabidiol	DM0659E	Approved	Cannabidiol increases the expression of Cilia- and flagella-associated protein 300 (CFAP300).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Cilia- and flagella-associated protein 300 (CFAP300).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Arsenic	DMTL2Y1	Approved	Arsenic increases the methylation of Cilia- and flagella-associated protein 300 (CFAP300).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Cilia- and flagella-associated protein 300 (CFAP300).	[8]

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] C11orf70 Mutations Disrupting the Intraflagellar Transport-Dependent Assembly of Multiple Axonemal Dyneins Cause Primary Ciliary Dyskinesia. Am J Hum Genet. 2018 May 3;102(5):956-972. doi: 10.1016/j.ajhg.2018.03.024.
• [3] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [4] Epigenetic changes in individuals with arsenicosis. Chem Res Toxicol. 2011 Feb 18;24(2):165-7. doi: 10.1021/tx1004419. Epub 2011 Feb 4.
• [5] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [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] Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells. J Cell Biochem. 2017 Jun;118(6):1531-1546. doi: 10.1002/jcb.25815. Epub 2016 Dec 29.
• [8] 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.
• [9] 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.