Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTUQO14U)

• DOT Name: Ciliogenesis and planar polarity effector 2 (CPLANE2)
• Synonyms: REM2- and Rab-like small GTPase 1
• Gene Name: CPLANE2
• Related Disease:
  Ciliopathy
  Hereditary hemochromatosis
• UniProt ID: CPLN2_HUMAN
• Pfam ID: PF00071
• Sequence:
  MARPPVPGSVVVPNWHESAEGKEYLACILRKNRRRVFGLLERPVLLPPVSIDTASYKIFV
  SGKSGVGKTALVAKLAGLEVPVVHHETTGIQTTVVFWPAKLQASSRVVMFRFEFWDCGES
  ALKKFDHMLLACMENTDAFLFLFSFTDRASFEDLPGQLARIAGEAPGVVRMVIGSKFDQY
  MHTDVPERDLTAFRQAWELPLLRVKSVPGRRLADGRTLDGRAGLADVAHILNGLAEQLWH
  QDQVAAGLLPNPPESAPE
• Function: Potential effector of the planar cell polarity signaling pathway. Plays a role in targeted membrane trafficking most probably at the level of vesicle fusion with membranes. Involved in cilium biogenesis by regulating the transport of cargo proteins to the basal body and to the apical tips of cilia. More generally involved in exocytosis in secretory cells.

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[1]
Hereditary hemochromatosis	DISVG5MT	Strong	Biomarker	[2]

2 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 Ciliogenesis and planar polarity effector 2 (CPLANE2).	[3]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Ciliogenesis and planar polarity effector 2 (CPLANE2).	[4]

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 decreases the methylation of Ciliogenesis and planar polarity effector 2 (CPLANE2).	[5]

References

• [1] Hexa-Longin domain scaffolds for inter-Rab signalling.Bioinformatics. 2020 Feb 15;36(4):990-993. doi: 10.1093/bioinformatics/btz739.
• [2] Small GTPases in hedgehog signalling: emerging insights into the disease mechanisms of Rab23-mediated and Arl13b-mediated ciliopathies.Curr Opin Genet Dev. 2019 Jun;56:61-68. doi: 10.1016/j.gde.2019.07.009. Epub 2019 Aug 27.
• [3] 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.
• [4] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [5] 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.