Details of Drug Off-Target (DOT)

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

• DOT Name: Tectonic-3 (TCTN3)
• Gene Name: TCTN3
• Related Disease:
  Ciliopathy
  Holoprosencephaly
  Neural tube defect
  Orofaciodigital syndrome IV
  Bone development disease
  Intellectual disability
  Joubert syndrome
  Joubert syndrome 18
  Polydactyly
  Short rib-polydactyly syndrome
  Meckel syndrome
  Orofaciodigital syndrome type 6
• UniProt ID: TECT3_HUMAN
• Pfam ID: PF07773
• Sequence:
  MRTPQLALLQVFFLVFPDGVRPQPSSSPSGAVPTSLELQRGTDGGTLQSPSEATATRPAV
  PGLPTVVPTLVTPSAPGNRTVDLFPVLPICVCDLTPGACDINCCCDRDCYLLHPRTVFSF
  CLPGSVRSSSWVCVDNSVIFRSNSPFPSRVFMDSNGIRQFCVHVNNSNLNYFQKLQKVNA
  TNFQALAAEFGGESFTSTFQTQSPPSFYRAGDPILTYFPKWSVISLLRQPAGVGAGGLCA
  ESNPAGFLESKSTTCTRFFKNLASSCTLDSALNAASYYNFTVLKVPRSMTDPQNMEFQVP
  VILTSQANAPLLAGNTCQNVVSQVTYEIETNGTFGIQKVSVSLGQTNLTVEPGASLQQHF
  ILRFRAFQQSTAASLTSPRSGNPGYIVGKPLLALTDDISYSMTLLQSQGNGSCSVKRHEV
  QFGVNAISGCKLRLKKADCSHLQQEIYQTLHGRPRPEYVAIFGNADPAQKGGWTRILNRH
  CSISAINCTSCCLIPVSLEIQVLWAYVGLLSNPQAHVSGVRFLYQCQSIQDSQQVTEVSL
  TTLVNFVDITQKPQPPRGQPKMDWKWPFDFFPFKVAFSRGVFSQKCSVSPILILCLLLLG
  VLNLETM
• Function: Part of the tectonic-like complex which is required for tissue-specific ciliogenesis and may regulate ciliary membrane composition. May be involved in apoptosis regulation. Necessary for signal transduction through the sonic hedgehog (Shh) signaling pathway.
• Reactome Pathway: Anchoring of the basal body to the plasma membrane (R-HSA-5620912)

Molecular Interaction Atlas (MIA) of This DOT

12 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Ciliopathy	DIS10G4I	Definitive	Autosomal recessive	[1]
Holoprosencephaly	DISR35EC	Definitive	Genetic Variation	[2]
Neural tube defect	DIS5J95E	Definitive	Biomarker	[3]
Orofaciodigital syndrome IV	DISWHOML	Definitive	Autosomal recessive	[4]
Bone development disease	DISVKAZS	Strong	Genetic Variation	[4]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[5]
Joubert syndrome	DIS7P5CO	Strong	Biomarker	[5]
Joubert syndrome 18	DISSVY6H	Strong	Autosomal recessive	[4]
Polydactyly	DIS25BMZ	Strong	Biomarker	[4]
Short rib-polydactyly syndrome	DISY2RES	Strong	Genetic Variation	[4]
Meckel syndrome	DISXPHOY	Supportive	Autosomal recessive	[4]
Orofaciodigital syndrome type 6	DISQY7K4	Supportive	Autosomal recessive	[4]

6 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 Tectonic-3 (TCTN3).	[6]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Tectonic-3 (TCTN3).	[7]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Tectonic-3 (TCTN3).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tectonic-3 (TCTN3).	[9]
Arsenic	DMTL2Y1	Approved	Arsenic affects the expression of Tectonic-3 (TCTN3).	[10]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Tectonic-3 (TCTN3).	[11]

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] Three Tctn proteins are functionally conserved in the regulation of neural tube patterning and Gli3 processing but not ciliogenesis and Hedgehog signaling in the mouse.Dev Biol. 2017 Oct 1;430(1):156-165. doi: 10.1016/j.ydbio.2017.08.003. Epub 2017 Aug 8.
• [3] Loss of Tctn3 causes neuronal apoptosis and neural tube defects in mice.Cell Death Dis. 2018 May 1;9(5):520. doi: 10.1038/s41419-018-0563-4.
• [4] TCTN3 mutations cause Mohr-Majewski syndrome. Am J Hum Genet. 2012 Aug 10;91(2):372-8. doi: 10.1016/j.ajhg.2012.06.017.
• [5] Tectonic gene mutations in patients with Joubert syndrome.Eur J Hum Genet. 2015 May;23(5):616-20. doi: 10.1038/ejhg.2014.160. Epub 2014 Aug 13.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [8] 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.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Drinking-water arsenic exposure modulates gene expression in human lymphocytes from a U.S. population. Environ Health Perspect. 2008 Apr;116(4):524-31. doi: 10.1289/ehp.10861.
• [11] 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.