Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0FUHLH)

• DOT Name: Stathmin-2 (STMN2)
• Synonyms: Superior cervical ganglion-10 protein; Protein SCG10
• Gene Name: STMN2
• Related Disease:
  Cone-rod dystrophy 2
  Alzheimer disease
  Ataxia-telangiectasia
  Creutzfeldt Jacob disease
  Major depressive disorder
  Neuroblastoma
  Osteoarthritis
  Parkinson disease
  Prion disease
  Riley-Day syndrome
  Schizophrenia
  Amyotrophic lateral sclerosis
  Hirschsprung disease
  Frontotemporal dementia
  Neuroblastic tumor
• UniProt ID: STMN2_HUMAN
• Pfam ID: PF00836
• Sequence:
  MAKTAMAYKEKMKELSMLSLICSCFYPEPRNINIYTYDDMEVKQINKRASGQAFELILKP
  PSPISEAPRTLASPKKKDLSLEEIQKKLEAAEERRKSQEAQVLKQLAEKREHEREVLQKA
  LEENNNFSKMAEEKLILKMEQIKENREANLAAIIERLQEKERHAAEVRRNKELQVELSG
• Function: Regulator of microtubule stability. When phosphorylated by MAPK8, stabilizes microtubules and consequently controls neurite length in cortical neurons. In the developing brain, negatively regulates the rate of exit from multipolar stage and retards radial migration from the ventricular zone.
• Tissue Specificity: Neuron specific.
• Reactome Pathway: RND1 GTPase cycle (R-HSA-9696273)

Molecular Interaction Atlas (MIA) of This DOT

15 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Cone-rod dystrophy 2	DISX2RWY	Definitive	Biomarker	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Ataxia-telangiectasia	DISP3EVR	Strong	Biomarker	[3]
Creutzfeldt Jacob disease	DISCB6RX	Strong	Genetic Variation	[4]
Major depressive disorder	DIS4CL3X	Strong	Genetic Variation	[5]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[6]
Osteoarthritis	DIS05URM	Strong	Genetic Variation	[7]
Parkinson disease	DISQVHKL	Strong	Altered Expression	[8]
Prion disease	DISOUMB0	Strong	Altered Expression	[9]
Riley-Day syndrome	DISJZHNP	Strong	Altered Expression	[6]
Schizophrenia	DISSRV2N	Strong	Altered Expression	[10]
Amyotrophic lateral sclerosis	DISF7HVM	moderate	Biomarker	[11]
Hirschsprung disease	DISUUSM1	moderate	Biomarker	[12]
Frontotemporal dementia	DISKYHXL	Disputed	Biomarker	[11]
Neuroblastic tumor	DISKWPS1	Limited	Altered Expression	[13]

11 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 Stathmin-2 (STMN2).	[14]
Cisplatin	DMRHGI9	Approved	Cisplatin affects the expression of Stathmin-2 (STMN2).	[15]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Stathmin-2 (STMN2).	[16]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Stathmin-2 (STMN2).	[17]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Stathmin-2 (STMN2).	[18]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Stathmin-2 (STMN2).	[15]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Stathmin-2 (STMN2).	[17]
Mifepristone	DMGZQEF	Approved	Mifepristone increases the expression of Stathmin-2 (STMN2).	[19]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Stathmin-2 (STMN2).	[17]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Stathmin-2 (STMN2).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Stathmin-2 (STMN2).	[21]

References

• [1] The Effect of Botulinum Neurotoxin Serotype a Heavy Chain on the Growth Related Proteins and Neurite Outgrowth after Spinal Cord Injury in Rats.Toxins (Basel). 2018 Feb 2;10(2):66. doi: 10.3390/toxins10020066.
• [2] SCG10 promotes non-amyloidogenic processing of amyloid precursor protein by facilitating its trafficking to the cell surface.Hum Mol Genet. 2013 Dec 15;22(24):4888-900. doi: 10.1093/hmg/ddt339. Epub 2013 Jul 17.
• [3] Functional and molecular defects of hiPSC-derived neurons from patients with ATM deficiency.Cell Death Dis. 2014 Jul 17;5(7):e1342. doi: 10.1038/cddis.2014.310.
• [4] RARB and STMN2 polymorphisms are not associated with sporadic Creutzfeldt-Jakob disease (CJD) in the Korean population.Mol Biol Rep. 2014;41(4):2389-95. doi: 10.1007/s11033-014-3093-x. Epub 2014 Jan 12.
• [5] The International SSRI Pharmacogenomics Consortium (ISPC): a genome-wide association study of antidepressant treatment response.Transl Psychiatry. 2015 Apr 21;5(4):e553. doi: 10.1038/tp.2015.47.
• [6] IKAP/Elp1 involvement in cytoskeleton regulation and implication for familial dysautonomia.Hum Mol Genet. 2011 Apr 15;20(8):1585-94. doi: 10.1093/hmg/ddr036. Epub 2011 Jan 27.
• [7] Identification of new susceptibility loci for osteoarthritis (arcOGEN): a genome-wide association study.Lancet. 2012 Sep 1;380(9844):815-23. doi: 10.1016/S0140-6736(12)60681-3. Epub 2012 Jul 3.
• [8] The landscape of multiscale transcriptomic networks and key regulators in Parkinson's disease.Nat Commun. 2019 Nov 20;10(1):5234. doi: 10.1038/s41467-019-13144-y.
• [9] Genetic risk factors for variant Creutzfeldt-Jakob disease: a genome-wide association study.Lancet Neurol. 2009 Jan;8(1):57-66. doi: 10.1016/S1474-4422(08)70265-5.
• [10] Reduced myelin basic protein and actin-related gene expression in visual cortex in schizophrenia.PLoS One. 2012;7(6):e38211. doi: 10.1371/journal.pone.0038211. Epub 2012 Jun 1.
• [11] Premature polyadenylation-mediated loss of stathmin-2 is a hallmark of TDP-43-dependent neurodegeneration.Nat Neurosci. 2019 Feb;22(2):180-190. doi: 10.1038/s41593-018-0293-z. Epub 2019 Jan 14.
• [12] Mutations in SCG10 are not involved in Hirschsprung disease.PLoS One. 2010 Dec 20;5(12):e15144. doi: 10.1371/journal.pone.0015144.
• [13] Kidins220/ARMS depletion is associated with the neural-to Schwann-like transition in a human neuroblastoma cell line model.Exp Cell Res. 2013 Mar 10;319(5):660-9. doi: 10.1016/j.yexcr.2012.12.027. Epub 2013 Jan 16.
• [14] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [15] Acute hypersensitivity of pluripotent testicular cancer-derived embryonal carcinoma to low-dose 5-aza deoxycytidine is associated with global DNA Damage-associated p53 activation, anti-pluripotency and DNA demethylation. PLoS One. 2012;7(12):e53003. doi: 10.1371/journal.pone.0053003. Epub 2012 Dec 27.
• [16] 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.
• [17] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [18] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [19] Mifepristone induced progesterone withdrawal reveals novel regulatory pathways in human endometrium. Mol Hum Reprod. 2007 Sep;13(9):641-54.
• [20] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [21] 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.