Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTV057AG)

• DOT Name: Neurexophilin-4 (NXPH4)
• Gene Name: NXPH4
• Related Disease: Gout
• UniProt ID: NXPH4_HUMAN
• Pfam ID: PF06312
• Sequence:
  MRLLPEWFLLLFGPWLLRKAVSAQIPESGRPQYLGLRPAAAGAGAPGQQLPEPRSSDGLG
  VGRAWSWAWPTNHTGALARAGAAGALPAQRTKRKPSIKAARAKKIFGWGDFYFRVHTLKF
  SLLVTGKIVDHVNGTFSVYFRHNSSSLGNLSVSIVPPSKRVEFGGVWLPGPVPHPLQSTL
  ALEGVLPGLGPPLGMAAAAAGPGLGGSLGGALAGPLGGALGVPGAKESRAFNCHVEYEKT
  NRARKHRPCLYDPSQVCFTEHTQSQAAWLCAKPFKVICIFVSFLSFDYKLVQKVCPDYNF
  QSEHPYFG
• Function: May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors.
• Tissue Specificity: Expressed in brain, spleen, and testis.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Gout	DISHC0U7	Strong	Genetic Variation	[1]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Decitabine	DMQL8XJ	Approved	Decitabine decreases the expression of Neurexophilin-4 (NXPH4).	[2]
Dexamethasone	DMMWZET	Approved	Dexamethasone decreases the expression of Neurexophilin-4 (NXPH4).	[3]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Neurexophilin-4 (NXPH4).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Neurexophilin-4 (NXPH4).	[5]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A affects the expression of Neurexophilin-4 (NXPH4).	[7]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Neurexophilin-4 (NXPH4).	[8]
Acetaldehyde	DMJFKG4	Investigative	Acetaldehyde increases the expression of Neurexophilin-4 (NXPH4).	[9]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the methylation of Neurexophilin-4 (NXPH4).	[6]

References

• [1] Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet. 2013 Feb;45(2):145-54. doi: 10.1038/ng.2500. Epub 2012 Dec 23.
• [2] DNA methylation inhibits p53-mediated survivin repression. Oncogene. 2009 May 14;28(19):2046-50. doi: 10.1038/onc.2009.62. Epub 2009 Apr 13.
• [3] Identification of mechanisms of action of bisphenol a-induced human preadipocyte differentiation by transcriptional profiling. Obesity (Silver Spring). 2014 Nov;22(11):2333-43.
• [4] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [5] Exome-wide mutation profile in benzo[a]pyrene-derived post-stasis and immortal human mammary epithelial cells. Mutat Res Genet Toxicol Environ Mutagen. 2014 Dec;775-776:48-54. doi: 10.1016/j.mrgentox.2014.10.011. Epub 2014 Nov 4.
• [6] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
• [7] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.
• [8] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.
• [9] Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.