Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG82U2K)

• DOT Name: Neurexophilin-3 (NXPH3)
• Gene Name: NXPH3
• Related Disease:
  Nephronophthisis 3
  Retinopathy
  Sjogren-Larsson syndrome
• UniProt ID: NXPH3_HUMAN
• Pfam ID: PF06312
• Sequence:
  MQLTRCCFVFLVQGSLYLVICGQDDGPPGSEDPERDDHEGQPRPRVPRKRGHISPKSRPM
  ANSTLLGLLAPPGEAWGILGQPPNRPNHSPPPSAKVKKIFGWGDFYSNIKTVALNLLVTG
  KIVDHGNGTFSVHFQHNATGQGNISISLVPPSKAVEFHQEQQIFIEAKASKIFNCRMEWE
  KVERGRRTSLCTHDPAKICSRDHAQSSATWSCSQPFKVVCVYIAFYSTDYRLVQKVCPDY
  NYHSDTPYYPSG
• Function: May be signaling molecules that resemble neuropeptides. Ligand for alpha-neurexins.
• Tissue Specificity: Highest level in brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephronophthisis 3	DIS4CC6R	moderate	Genetic Variation	[1]
Retinopathy	DISB4B0F	moderate	Biomarker	[1]
Sjogren-Larsson syndrome	DISP943Y	moderate	Genetic Variation	[1]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Neurexophilin-3 (NXPH3).	[2]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Neurexophilin-3 (NXPH3).	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Neurexophilin-3 (NXPH3).	[3]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neurexophilin-3 (NXPH3).	[4]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Neurexophilin-3 (NXPH3).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Neurexophilin-3 (NXPH3).	[7]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Neurexophilin-3 (NXPH3).	[8]

References

• [1] Candidate gene analysis of KIAA0678 encoding a DnaJ-like protein for adolescent nephronophthisis and Senior-Lken syndrome type 3.Cytogenet Genome Res. 2002;97(3-4):163-6. doi: 10.1159/000066617.
• [2] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [3] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [4] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [5] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [6] 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.
• [7] 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.
• [8] 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.