Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1LOKOI)

• DOT Name: Transmembrane protein 216 (TMEM216)
• Gene Name: TMEM216
• Related Disease:
  Ciliopathy
  Joubert syndrome
  Joubert syndrome 2
  Meckel syndrome, type 1
  Joubert syndrome with oculorenal defect
  Meckel syndrome
  Orofaciodigital syndrome type 6
• UniProt ID: TM216_HUMAN
• Pfam ID: PF09799
• Sequence:
  MLPRGLKMAPRGKRLSSTPLEILFFLNGWYNATYFLLELFIFLYKGVLLPYPTANLVLDV
  VMLLLYLGIEVIRLFFGTKGNLCQRKMPLSISVALTFPSAMMASYYLLLQTYVLRLEAIM
  NGILLFFCGSELLLEVLTLAAFSRI
• Function: Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition.
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliopathy	DIS10G4I	Strong	Genetic Variation	[1]
Joubert syndrome	DIS7P5CO	Strong	CausalMutation	[2]
Joubert syndrome 2	DIS8PDVU	Strong	Autosomal recessive	[3]
Meckel syndrome, type 1	DIS4YWZU	Strong	Biomarker	[4]
Joubert syndrome with oculorenal defect	DISU0IPO	Supportive	Autosomal recessive	[5]
Meckel syndrome	DISXPHOY	Supportive	Autosomal recessive	[6]
Orofaciodigital syndrome type 6	DISQY7K4	Supportive	Autosomal recessive	[7]

3 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 Transmembrane protein 216 (TMEM216).	[8]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Transmembrane protein 216 (TMEM216).	[9]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Transmembrane protein 216 (TMEM216).	[10]

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 affects the methylation of Transmembrane protein 216 (TMEM216).	[11]

References

• [1] Evolutionarily assembled cis-regulatory module at a human ciliopathy locus. Science. 2012 Feb 24;335(6071):966-9. doi: 10.1126/science.1213506. Epub 2012 Jan 26.
• [2] Neuropsychological phenotypes of 76 individuals with Joubert syndrome evaluated at a single center.Am J Med Genet A. 2017 Jul;173(7):1796-1812. doi: 10.1002/ajmg.a.38272. Epub 2017 May 12.
• [3] Mutations in TMEM216 perturb ciliogenesis and cause Joubert, Meckel and related syndromes. Nat Genet. 2010 Jul;42(7):619-25. doi: 10.1038/ng.594. Epub 2010 May 30.
• [4] Joubert syndrome 2 (JBTS2) in Ashkenazi Jews is associated with a TMEM216 mutation. Am J Hum Genet. 2010 Jan;86(1):93-7. doi: 10.1016/j.ajhg.2009.12.007. Epub 2009 Dec 31.
• [5] Joubert Syndrome. 2003 Jul 9 [updated 2017 Jun 29]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [6] Molecular genetics and pathogenic mechanisms for the severe ciliopathies: insights into neurodevelopment and pathogenesis of neural tube defects. Mol Neurobiol. 2011 Feb;43(1):12-26. doi: 10.1007/s12035-010-8154-0. Epub 2010 Nov 27.
• [7] Joubert Syndrome and related disorders. Orphanet J Rare Dis. 2010 Jul 8;5:20. doi: 10.1186/1750-1172-5-20.
• [8] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [9] 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.
• [10] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [11] 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.