Details of Drug Off-Target (DOT)

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

• DOT Name: Neuroplastin (NPTN)
• Synonyms: Stromal cell-derived receptor 1; SDR-1
• Gene Name: NPTN
• Related Disease:
  Advanced cancer
  Acute erythroid leukemia
  Alzheimer disease
  Anxiety
  Anxiety disorder
  Atopic dermatitis
  Breast cancer
  Breast carcinoma
  Breast neoplasm
  Depression
  Dermatitis
  Epilepsy
  Hereditary nonpolyposis colon cancer
  High blood pressure
  Lung cancer
  Lung carcinoma
  Lynch syndrome
  Mental disorder
  Myocardial ischemia
  Neoplasm
  Obesity
  Polycythemia
  Schizophrenia
  Stroke
  Lung neoplasm
• UniProt ID: NPTN_HUMAN
• PDB ID: 6A69
• Pfam ID: PF13927
• Sequence:
  MSGSSLPSALALSLLLVSGSLLPGPGAAQNAGFVKSPMSETKLTGDAFELYCDVVGSPTP
  EIQWWYAEVNRAESFRQLWDGARKRRVTVNTAYGSNGVSVLRITRLTLEDSGTYECRASN
  DPKRNDLRQNPSITWIRAQATISVLQKPRIVTSEEVIIRDSPVLPVTLQCNLTSSSHTLT
  YSYWTKNGVELSATRKNASNMEYRINKPRAEDSGEYHCVYHFVSAPKANATIEVKAAPDI
  TGHKRSENKNEGQDATMYCKSVGYPHPDWIWRKKENGMPMDIVNTSGRFFIINKENYTEL
  NIVNLQITEDPGEYECNATNAIGSASVVTVLRVRSHLAPLWPFLGILAEIIILVVIIVVY
  EKRKRPDEVPDDDEPAGPMKTNSTNNHKDKNLRQRNTN
• Function: Probable homophilic and heterophilic cell adhesion molecule involved in long term potentiation at hippocampal excitatory synapses through activation of p38MAPK. May also regulate neurite outgrowth by activating the FGFR1 signaling pathway. May play a role in synaptic plasticity. Also acts as a chaperone for ATP2B1; stabilizes ATP2B1 and increases its ATPase activity. Promotes localization of XKR8 at the cell membrane.
• Tissue Specificity: Isoform 1 is ubiquitously expressed. Isoform 2 is expressed in brain cortex and cerebellum (at protein level).
• Reactome Pathway: GABA receptor activation (R-HSA-977443)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Advanced cancer	DISAT1Z9	Definitive	Biomarker	[1]
Acute erythroid leukemia	DISZFC1O	Strong	Biomarker	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Anxiety	DISIJDBA	Strong	Biomarker	[4]
Anxiety disorder	DISBI2BT	Strong	Biomarker	[4]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[5]
Breast cancer	DIS7DPX1	Strong	Genetic Variation	[6]
Breast carcinoma	DIS2UE88	Strong	Genetic Variation	[6]
Breast neoplasm	DISNGJLM	Strong	Biomarker	[7]
Depression	DIS3XJ69	Strong	Biomarker	[8]
Dermatitis	DISY5SZC	Strong	Biomarker	[9]
Epilepsy	DISBB28L	Strong	Genetic Variation	[10]
Hereditary nonpolyposis colon cancer	DISPA49R	Strong	Biomarker	[11]
High blood pressure	DISY2OHH	Strong	Biomarker	[12]
Lung cancer	DISCM4YA	Strong	Biomarker	[5]
Lung carcinoma	DISTR26C	Strong	Biomarker	[5]
Lynch syndrome	DIS3IW5F	Strong	Biomarker	[11]
Mental disorder	DIS3J5R8	Strong	Biomarker	[4]
Myocardial ischemia	DISFTVXF	Strong	Biomarker	[13]
Neoplasm	DISZKGEW	Strong	Altered Expression	[7]
Obesity	DIS47Y1K	Strong	Genetic Variation	[10]
Polycythemia	DIS8B6VW	Strong	Biomarker	[14]
Schizophrenia	DISSRV2N	Strong	Biomarker	[8]
Stroke	DISX6UHX	moderate	Altered Expression	[15]
Lung neoplasm	DISVARNB	Limited	Biomarker	[16]

13 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 Neuroplastin (NPTN).	[17]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Neuroplastin (NPTN).	[18]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Neuroplastin (NPTN).	[19]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Neuroplastin (NPTN).	[20]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Neuroplastin (NPTN).	[21]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Neuroplastin (NPTN).	[22]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Neuroplastin (NPTN).	[23]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Neuroplastin (NPTN).	[24]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Neuroplastin (NPTN).	[25]
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Neuroplastin (NPTN).	[26]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of Neuroplastin (NPTN).	[27]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the mutagenesis of Neuroplastin (NPTN).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Neuroplastin (NPTN).	[29]

References

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• [15] Increased Susceptibility to Ischemic Brain Injury in Neuroplastin 65-Deficient Mice Likely via Glutamate Excitotoxicity.Front Cell Neurosci. 2017 Apr 19;11:110. doi: 10.3389/fncel.2017.00110. eCollection 2017.
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• [19] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
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• [22] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
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