Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTGKX860)

• DOT Name: Neurexophilin-1 (NXPH1)
• Gene Name: NXPH1
• Related Disease:
  Autism spectrum disorder
  Chronic renal failure
  Constipation
  Dandy-Walker syndrome
  End-stage renal disease
  Irritable bowel syndrome
  Joubert syndrome
  Kidney failure
  Narcolepsy
  Nephronophthisis
  Nephronophthisis 1
  Normal pressure hydrocephalus
  Obesity
  Nephropathy
  Autoimmune polyendocrinopathy
  Intellectual disability
• UniProt ID: NXPH1_HUMAN
• Pfam ID: PF06312
• Sequence:
  MQAACWYVLFLLQPTVYLVTCANLTNGGKSELLKSGSSKSTLKHIWTESSKDLSISRLLS
  QTFRGKENDTDLDLRYDTPEPYSEQDLWDWLRNSTDLQEPRPRAKRRPIVKTGKFKKMFG
  WGDFHSNIKTVKLNLLITGKIVDHGNGTFSVYFRHNSTGQGNVSVSLVPPTKIVEFDLAQ
  QTVIDAKDSKSFNCRIEYEKVDKATKNTLCNYDPSKTCYQEQTQSHVSWLCSKPFKVICI
  YISFYSTDYKLVQKVCPDYNYHSDTPYFPSG
• Function: May be signaling molecules that resemble neuropeptides and that act by binding to alpha-neurexins and possibly other receptors.

Molecular Interaction Atlas (MIA) of This DOT

16 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[1]
Chronic renal failure	DISGG7K6	Strong	Biomarker	[2]
Constipation	DISRQXWI	Strong	Genetic Variation	[3]
Dandy-Walker syndrome	DIS4HC6W	Strong	Genetic Variation	[4]
End-stage renal disease	DISXA7GG	Strong	Biomarker	[2]
Irritable bowel syndrome	DIS27206	Strong	Genetic Variation	[3]
Joubert syndrome	DIS7P5CO	Strong	Genetic Variation	[4]
Kidney failure	DISOVQ9P	Strong	Genetic Variation	[2]
Narcolepsy	DISLCNLI	Strong	Genetic Variation	[5]
Nephronophthisis	DISXU4HY	Strong	Biomarker	[6]
Nephronophthisis 1	DIS7QNQ3	Strong	Genetic Variation	[4]
Normal pressure hydrocephalus	DISOEFO9	Strong	Genetic Variation	[7]
Obesity	DIS47Y1K	Strong	Biomarker	[8]
Nephropathy	DISXWP4P	Disputed	Genetic Variation	[9]
Autoimmune polyendocrinopathy	DISOLDB2	Limited	Biomarker	[10]
Intellectual disability	DISMBNXP	Limited	Genetic Variation	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Neurexophilin-1 (NXPH1).	[12]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Neurexophilin-1 (NXPH1).	[13]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Neurexophilin-1 (NXPH1).	[12]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of Neurexophilin-1 (NXPH1).	[14]
Niclosamide	DMJAGXQ	Approved	Niclosamide decreases the expression of Neurexophilin-1 (NXPH1).	[15]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Neurexophilin-1 (NXPH1).	[17]

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 decreases the methylation of Neurexophilin-1 (NXPH1).	[16]

References

• [1] Copy number variants in extended autism spectrum disorder families reveal candidates potentially involved in autism risk.PLoS One. 2011;6(10):e26049. doi: 10.1371/journal.pone.0026049. Epub 2011 Oct 7.
• [2] Molecular genetic identification of families with juvenile nephronophthisis type 1: rate of progression to renal failure. APN Study Group. Arbeitsgemeinschaft fr Pdiatrische Nephrologie.Kidney Int. 1997 Jan;51(1):261-9. doi: 10.1038/ki.1997.31.
• [3] Genetic variants in CDC42 and NXPH1 as susceptibility factors for constipation and diarrhoea predominant irritable bowel syndrome.Gut. 2014 Jul;63(7):1103-11. doi: 10.1136/gutjnl-2013-304570. Epub 2013 Sep 16.
• [4] Clinical nosologic and genetic aspects of Joubert and related syndromes.J Child Neurol. 1999 Oct;14(10):660-6; discussion 669-72. doi: 10.1177/088307389901401007.
• [5] Genome-wide association database developed in the Japanese Integrated Database Project.J Hum Genet. 2009 Sep;54(9):543-6. doi: 10.1038/jhg.2009.68. Epub 2009 Jul 24.
• [6] The genes and proteins associated with poly-cystic kidney diseases.Minerva Urol Nefrol. 2002 Dec;54(4):201-11.
• [7] Lack of large, homozygous deletions of the nephronophthisis 1 region in Joubert syndrome type B. APN Study Group. Arbeitsgemeinschaft fr Pdiatrische Nephrologie.Pediatr Nephrol. 1998 Jan;12(1):16-9. doi: 10.1007/s004670050394.
• [8] Maternal BMI as a predictor of methylation of obesity-related genes in saliva samples from preschool-age Hispanic children at-risk for obesity.BMC Genomics. 2017 Jan 9;18(1):57. doi: 10.1186/s12864-016-3473-9.
• [9] A 11 Mb YAC-based contig spanning the familial juvenile nephronophthisis region (NPH1) located on chromosome 2q.Genomics. 1995 Dec 10;30(3):514-20. doi: 10.1006/geno.1995.1272.
• [10] Beneficial effects of astragalus polysaccharides treatment on cardiac chymase activities and cardiomyopathy in diabetic hamsters.Acta Diabetol. 2010 Dec;47 Suppl 1:35-46. doi: 10.1007/s00592-009-0116-5. Epub 2009 Apr 7.
• [11] Molecular karyotyping in patients with mental retardation using 100K single-nucleotide polymorphism arrays.J Med Genet. 2007 Oct;44(10):629-36. doi: 10.1136/jmg.2007.050914. Epub 2007 Jun 29.
• [12] 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.
• [13] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [14] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [15] 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.
• [16] 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.
• [17] CCAT1 is an enhancer-templated RNA that predicts BET sensitivity in colorectal cancer. J Clin Invest. 2016 Feb;126(2):639-52.