Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT4NEBNO)

• DOT Name: Magnesium transporter NIPA2 (NIPA2)
• Synonyms: Non-imprinted in Prader-Willi/Angelman syndrome region protein 2
• Gene Name: NIPA2
• Related Disease:
  Angelman syndrome
  Non-insulin dependent diabetes
  Osteoporosis
  Prostate neoplasm
  Prader-Willi syndrome
  Absence epilepsy
  Absence seizure
  Epilepsy
• UniProt ID: NIPA2_HUMAN
• Pfam ID: PF05653
• Sequence:
  MSQGRGKYDFYIGLGLAMSSSIFIGGSFILKKKGLLRLARKGSMRAGQGGHAYLKEWLWW
  AGLLSMGAGEVANFAAYAFAPATLVTPLGALSVLVSAILSSYFLNERLNLHGKIGCLLSI
  LGSTVMVIHAPKEEEIETLNEMSHKLGDPGFVVFATLVVIVALILIFVVGPRHGQTNILV
  YITICSVIGAFSVSCVKGLGIAIKELFAGKPVLRHPLAWILLLSLIVCVSTQINYLNRAL
  DIFNTSIVTPIYYVFFTTSVLTCSAILFKEWQDMPVDDVIGTLSGFFTIIVGIFLLHAFK
  DVSFSLASLPVSFRKDEKAMNGNLSNMYEVLNNNEESLTCGIEQHTGENVSRRNGNLTAF
• Function: Acts as a selective Mg(2+) transporter.
• Tissue Specificity: Widely expressed.
• Reactome Pathway: Miscellaneous transport and binding events (R-HSA-5223345)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Angelman syndrome	DIS4QVXO	Definitive	Genetic Variation	[1]
Non-insulin dependent diabetes	DISK1O5Z	Strong	Biomarker	[2]
Osteoporosis	DISF2JE0	Strong	Biomarker	[2]
Prostate neoplasm	DISHDKGQ	Strong	Altered Expression	[3]
Prader-Willi syndrome	DISYWMLU	moderate	Altered Expression	[4]
Absence epilepsy	DISJPOUD	Limited	Genetic Variation	[5]
Absence seizure	DIS4709R	Limited	Genetic Variation	[5]
Epilepsy	DISBB28L	Limited	Genetic Variation	[5]

1 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 Magnesium transporter NIPA2 (NIPA2).	[6]

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 Magnesium transporter NIPA2 (NIPA2).	[7]

References

• [1] Clinical and genetic aspects of the 15q11.2 BP1-BP2 microdeletion disorder.J Intellect Disabil Res. 2017 Jun;61(6):568-579. doi: 10.1111/jir.12382. Epub 2017 Apr 7.
• [2] NIPA2 regulates osteoblast function via its effect on apoptosis pathways in type 2 diabetes osteoporosis.Biochem Biophys Res Commun. 2019 Jun 11;513(4):883-890. doi: 10.1016/j.bbrc.2019.04.030. Epub 2019 Apr 16.
• [3] Gene expression profiling predicts clinical outcome of prostate cancer.J Clin Invest. 2004 Mar;113(6):913-23. doi: 10.1172/JCI20032.
• [4] Expression of 4 genes between chromosome 15 breakpoints 1 and 2 and behavioral outcomes in Prader-Willi syndrome.Pediatrics. 2006 Oct;118(4):e1276-83. doi: 10.1542/peds.2006-0424. Epub 2006 Sep 18.
• [5] The absence of NIPA2 enhances neural excitability through BK (big potassium) channels.CNS Neurosci Ther. 2019 Aug;25(8):865-875. doi: 10.1111/cns.13119. Epub 2019 Mar 20.
• [6] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [7] 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.