Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXP9A63)

• DOT Name: Neuropilin and tolloid-like protein 1 (NETO1)
• Synonyms: Brain-specific transmembrane protein containing 2 CUB and 1 LDL-receptor class A domains protein 1
• Gene Name: NETO1
• Related Disease:
  Advanced cancer
  Alzheimer disease
  Autism
  Schizophrenia
• UniProt ID: NETO1_HUMAN
• Pfam ID: PF00431 ; PF00057
• Sequence:
  MIHGRSVLHIVASLIILHLSGATKKGTEKQTTSETQKSVQCGTWTKHAEGGIFTSPNYPS
  KYPPDRECIYIIEAAPRQCIELYFDEKYSIEPSWECKFDHIEVRDGPFGFSPIIGRFCGQ
  QNPPVIKSSGRFLWIKFFADGELESMGFSARYNFTPDPDFKDLGALKPLPACEFEMGGSE
  GIVESIQIMKEGKATASEAVDCKWYIRAPPRSKIYLRFLDYEMQNSNECKRNFVAVYDGS
  SSVEDLKAKFCSTVANDVMLRTGLGVIRMWADEGSRNSRFQMLFTSFQEPPCEGNTFFCH
  SNMCINNTLVCNGLQNCVYPWDENHCKEKRKTSLLDQLTNTSGTVIGVTSCIVIILIIIS
  VIVQIKQPRKKYVQRKSDFDQTVFQEVFEPPHYELCTLRGTGATADFADVADDFENYHKL
  RRSSSKCIHDHHCGSQLSSTKGSRSNLSTRDASILTEMPTQPGKPLIPPMNRRNILVMKH
  SYSQDAADACDIDEIEEVPTTSHRLSRHDKAVQRFCLIGSLSKHESEYNTTRV
• Function: Involved in the development and/or maintenance of neuronal circuitry. Accessory subunit of the neuronal N-methyl-D-aspartate receptor (NMDAR) critical for maintaining the abundance of GRIN2A-containing NMDARs in the postsynaptic density. Regulates long-term NMDA receptor-dependent synaptic plasticity and cognition, at least in the context of spatial learning and memory.
• Tissue Specificity: Isoform 1 and isoform 2 are retina-specific. Isoform 3 is found in retina as well as at lower levels in adult and fetal brain.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Strong	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Strong	Genetic Variation	[1]
Autism	DISV4V1Z	Strong	Biomarker	[2]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[3]

11 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 Neuropilin and tolloid-like protein 1 (NETO1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[7]
Estradiol	DMUNTE3	Approved	Estradiol affects the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[8]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[9]
Testosterone	DM7HUNW	Approved	Testosterone decreases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[9]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[10]
Decitabine	DMQL8XJ	Approved	Decitabine increases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[13]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Neuropilin and tolloid-like protein 1 (NETO1).	[14]

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 Neuropilin and tolloid-like protein 1 (NETO1).	[12]

References

• [1] A genome-wide association study of aging.Neurobiol Aging. 2011 Nov;32(11):2109.e15-28. doi: 10.1016/j.neurobiolaging.2011.05.026. Epub 2011 Jul 22.
• [2] Genetic determinants of autism in individuals with deletions of 18q.Hum Genet. 2010 Aug;128(2):155-64. doi: 10.1007/s00439-010-0839-y. Epub 2010 May 25.
• [3] A case control association study and cognitive function analysis of neuropilin and tolloid-like 1 gene and schizophrenia in the Japanese population.PLoS One. 2011;6(12):e28929. doi: 10.1371/journal.pone.0028929. Epub 2011 Dec 20.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [6] 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.
• [7] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
• [9] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [10] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [11] Characterization of DOK1, a candidate tumor suppressor gene, in epithelial ovarian cancer. Mol Oncol. 2011 Oct;5(5):438-53. doi: 10.1016/j.molonc.2011.07.003. Epub 2011 Jul 26.
• [12] 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.
• [13] 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.
• [14] Cellular reactions to long-term volatile organic compound (VOC) exposures. Sci Rep. 2016 Dec 1;6:37842. doi: 10.1038/srep37842.