Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKR3I3L)

• DOT Name: Tectonic-2 (TCTN2)
• Gene Name: TCTN2
• Related Disease:
  Joubert syndrome 1
  Joubert syndrome 24
  Polydactyly
  Postaxial polydactyly
  Ciliopathy
  Meckel syndrome, type 1
  Neoplasm
  Nephronophthisis
  Ovarian cancer
  Joubert syndrome
  Meckel syndrome
• UniProt ID: TECT2_HUMAN
• Pfam ID: PF07773
• Sequence:
  MGFQPPAALLLRLFLLQGILRLLWGDLAFIPPFIRMSGPAVSASLVGDTEGVTVSLAVLQ
  DEAGILPIPTCGVLNNETEDWSVTVIPGAKVLEVTVRWKRGLDWCSSNETDSFSESPCIL
  QTLLVSASHNSSCSAHLLIQVEIYANSSLTHNASENVTVIPNQVYQPLGPCPCNLTAGAC
  DVRCCCDQECSSNLTTLFRRSCFTGVFGGDVNPPFDQLCSAGTTTRGVPDWFPFLCVQSP
  LANTPFLGYFYHGAVSPKQDSSFEVYVDTDAKDFADFGYKQGDPIMTVKKAYFTIPQVSL
  AGQCMQNAPVAFLHNFDVKCVTNLELYQERDGIINAKIKNVALGGIVTPKVIYEEATDLD
  KFITNTETPLNNGSTPRIVNVEEHYIFKWNNNTISEINVKIFRAEINAHQKGIMTQRFVV
  KFLSYNSGNEEELSGNPGYQLGKPVRALNINRMNNVTTLHLWQSAGRGLCTSATFKPILF
  GENVLSGCLLEVGINENCTQLRENAVERLDSLIQATHVAMRGNSDYADLSDGWLEIIRVD
  APDPGADPLASSVNGMCLDIPAHLSIRILISDAGAVEGITQQEILGVETRFSSVNWQYQC
  GLTCEHKADLLPISASVQFIKIPAQLPHPLTRFQINYTEYDCNRNEVCWPQLLYPWTQYY
  QGELHSQCVAKGLLLLLFLTLALFLSNPWTRICKAYS
• Function: Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. Required for hedgehog signaling transduction.
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Joubert syndrome 1	DISC9Q82	Definitive	GermlineCausalMutation	[1]
Joubert syndrome 24	DISHL7W9	Definitive	Autosomal recessive	[2]
Polydactyly	DIS25BMZ	Definitive	Biomarker	[3]
Postaxial polydactyly	DIS085OV	Definitive	Biomarker	[3]
Ciliopathy	DIS10G4I	Strong	Biomarker	[4]
Meckel syndrome, type 1	DIS4YWZU	Strong	Genetic Variation	[4]
Neoplasm	DISZKGEW	Strong	Biomarker	[5]
Nephronophthisis	DISXU4HY	Strong	Biomarker	[1]
Ovarian cancer	DISZJHAP	Strong	Altered Expression	[5]
Joubert syndrome	DIS7P5CO	Supportive	Autosomal recessive	[1]
Meckel syndrome	DISXPHOY	Supportive	Autosomal recessive	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tectonic-2 (TCTN2).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Tectonic-2 (TCTN2).	[7]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Tectonic-2 (TCTN2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Tectonic-2 (TCTN2).	[9]
Leflunomide	DMR8ONJ	Phase 1 Trial	Leflunomide decreases the expression of Tectonic-2 (TCTN2).	[11]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tectonic-2 (TCTN2).	[12]

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 Tectonic-2 (TCTN2).	[10]

References

• [1] Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell. 2011 May 13;145(4):513-28. doi: 10.1016/j.cell.2011.04.019.
• [2] 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.
• [3] A TCTN2 mutation defines a novel Meckel Gruber syndrome locus. Hum Mutat. 2011 Jun;32(6):573-8. doi: 10.1002/humu.21507. Epub 2011 May 5.
• [4] Super-Resolution Imaging Reveals TCTN2 Depletion-Induced IFT88 Lumen Leakage and CiliaryWeakening.Biophys J. 2018 Jul 17;115(2):263-275. doi: 10.1016/j.bpj.2018.04.051. Epub 2018 Jun 1.
• [5] TCTN2: a novel tumor marker with oncogenic properties.Oncotarget. 2017 Aug 24;8(56):95256-95269. doi: 10.18632/oncotarget.20438. eCollection 2017 Nov 10.
• [6] 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.
• [7] 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.
• [8] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [10] 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.
• [11] Endoplasmic reticulum stress and MAPK signaling pathway activation underlie leflunomide-induced toxicity in HepG2 Cells. Toxicology. 2017 Dec 1;392:11-21.
• [12] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.