Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTXD8ID1)

• DOT Name: Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2)
• Synonyms: Adapter protein X11beta; Neuron-specific X11L protein; Neuronal Munc18-1-interacting protein 2; Mint-2
• Gene Name: APBA2
• Related Disease:
  Adenocarcinoma
  Adenoma
  Advanced cancer
  Alzheimer disease
  Autism
  Autism spectrum disorder
  Carcinoma
  Colorectal carcinoma
  Gastric cancer
  Hepatitis
  Hepatitis A virus infection
  Pervasive developmental disorder
  Schizophrenia
  Skin disease
  Stomach cancer
  Tourette syndrome
  Gastrointestinal stromal tumour
  Kaposi sarcoma
  Epilepsy
  Familial adenomatous polyposis
  Neoplasm
• UniProt ID: APBA2_HUMAN
• Pfam ID: PF00595 ; PF00640
• Sequence:
  MAHRKLESVGSGMLDHRVRPGPVPHSQEPESEDMELPLEGYVPEGLELAALRPESPAPEE
  QECHNHSPDGDSSSDYVNNTSEEEDYDEGLPEEEEGITYYIRYCPEDDSYLEGMDCNGEE
  YLAHSAHPVDTDECQEAVEEWTDSAGPHPHGHEAEGSQDYPDGQLPIPEDEPSVLEAHDQ
  EEDGHYCASKEGYQDYYPEEANGNTGASPYRLRRGDGDLEDQEEDIDQIVAEIKMSLSMT
  SITSASEASPEHGPEPGPEDSVEACPPIKASCSPSRHEARPKSLNLLPEAKHPGDPQRGF
  KPKTRTPEERLKWPHEQVCNGLEQPRKQQRSDLNGPVDNNNIPETKKVASFPSFVAVPGP
  CEPEDLIDGIIFAANYLGSTQLLSERNPSKNIRMMQAQEAVSRVKRMQKAAKIKKKANSE
  GDAQTLTEVDLFISTQRIKVLNADTQETMMDHALRTISYIADIGNIVVLMARRRMPRSAS
  QDCIETTPGAQEGKKQYKMICHVFESEDAQLIAQSIGQAFSVAYQEFLRANGINPEDLSQ
  KEYSDIINTQEMYNDDLIHFSNSENCKELQLEKHKGEILGVVVVESGWGSILPTVILANM
  MNGGPAARSGKLSIGDQIMSINGTSLVGLPLATCQGIIKGLKNQTQVKLNIVSCPPVTTV
  LIKRPDLKYQLGFSVQNGIICSLMRGGIAERGGVRVGHRIIEINGQSVVATAHEKIVQAL
  SNSVGEIHMKTMPAAMFRLLTGQETPLYI
• Function: Putative function in synaptic vesicle exocytosis by binding to STXBP1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the amyloid-beta precursor protein (APP) and hence formation of APP-beta.
• Tissue Specificity: Brain.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

21 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Strong	Posttranslational Modification	[1]
Adenoma	DIS78ZEV	Strong	Biomarker	[2]
Advanced cancer	DISAT1Z9	Strong	Posttranslational Modification	[3]
Alzheimer disease	DISF8S70	Strong	Biomarker	[4]
Autism	DISV4V1Z	Strong	Genetic Variation	[5]
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[6]
Carcinoma	DISH9F1N	Strong	Biomarker	[7]
Colorectal carcinoma	DIS5PYL0	Strong	Posttranslational Modification	[8]
Gastric cancer	DISXGOUK	Strong	Biomarker	[9]
Hepatitis	DISXXX35	Strong	Posttranslational Modification	[10]
Hepatitis A virus infection	DISUMFQV	Strong	Posttranslational Modification	[10]
Pervasive developmental disorder	DIS51975	Strong	Biomarker	[11]
Schizophrenia	DISSRV2N	Strong	Biomarker	[12]
Skin disease	DISDW8R6	Strong	Biomarker	[13]
Stomach cancer	DISKIJSX	Strong	Biomarker	[9]
Tourette syndrome	DISX9D54	Strong	Biomarker	[14]
Gastrointestinal stromal tumour	DIS6TJYS	moderate	Posttranslational Modification	[15]
Kaposi sarcoma	DISC1H1Z	Disputed	Genetic Variation	[8]
Epilepsy	DISBB28L	Limited	Autosomal dominant	[16]
Familial adenomatous polyposis	DISW53RE	Limited	Biomarker	[17]
Neoplasm	DISZKGEW	Limited	Biomarker	[9]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Fluorouracil	DMUM7HZ	Approved	Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2) affects the response to substance of Fluorouracil.	[25]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[18]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[19]
Calcitriol	DM8ZVJ7	Approved	Calcitriol decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[20]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[21]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[22]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[24]

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 affects the methylation of Amyloid-beta A4 precursor protein-binding family A member 2 (APBA2).	[23]

References

• [1] Frequent CpG island methylation in precursor lesions and early gastric adenocarcinomas.Oncogene. 2004 Jun 3;23(26):4646-54. doi: 10.1038/sj.onc.1207588.
• [2] Frequent CpG island methylation in serrated adenomas of the colorectum.Am J Pathol. 2003 Mar;162(3):815-22. doi: 10.1016/S0002-9440(10)63878-3.
• [3] CpG island methylation in colorectal adenomas.Am J Pathol. 2001 Sep;159(3):1129-35. doi: 10.1016/S0002-9440(10)61789-0.
• [4] Protein-Protein Interactions and Aggregation Inhibitors in Alzheimer's Disease.Curr Top Med Chem. 2019;19(7):501-533. doi: 10.2174/1568026619666190304153353.
• [5] Copy number and sequence variants implicate APBA2 as an autism candidate gene.Autism Res. 2009 Dec;2(6):359-64. doi: 10.1002/aur.107.
• [6] A rare autism-associated MINT2/APBA2 mutation disrupts neurexin trafficking and synaptic function.Sci Rep. 2019 Apr 15;9(1):6024. doi: 10.1038/s41598-019-42635-7.
• [7] Role of DNA methylation in the development of Epstein-Barr virus-associated gastric carcinoma.J Med Virol. 2013 Jan;85(1):121-7. doi: 10.1002/jmv.23405. Epub 2012 Oct 16.
• [8] Detection of viral DNA sequences in sporadic colorectal cancers in relation to CpG island methylation and methylator phenotype.Tumour Biol. 2011 Aug;32(4):653-9. doi: 10.1007/s13277-011-0165-6. Epub 2011 Apr 6.
• [9] Circulating methylated MINT2 promoter DNA is a potential poor prognostic factor in gastric cancer.Dig Dis Sci. 2014 Jun;59(6):1160-8. doi: 10.1007/s10620-013-3007-0. Epub 2014 Jan 3.
• [10] Hypomethylation of long interspersed nuclear element-1 in hepatocellular carcinomas.Mod Pathol. 2009 Mar;22(3):442-9. doi: 10.1038/modpathol.2008.203. Epub 2009 Jan 9.
• [11] Altered social behavior in mice carrying a cortical Foxp2 deletion.Hum Mol Genet. 2019 Mar 1;28(5):701-717. doi: 10.1093/hmg/ddy372.
• [12] Comparative genome hybridization suggests a role for NRXN1 and APBA2 in schizophrenia.Hum Mol Genet. 2008 Feb 1;17(3):458-65. doi: 10.1093/hmg/ddm323. Epub 2007 Nov 6.
• [13] Association between genome-wide copy number variation and arsenic-induced skin lesions: a prospective study.Environ Health. 2017 Jul 18;16(1):75. doi: 10.1186/s12940-017-0283-8.
• [14] Gene expression changes in peripheral blood from Chinese Han patients with Tourette syndrome.Am J Med Genet B Neuropsychiatr Genet. 2012 Dec;159B(8):977-80. doi: 10.1002/ajmg.b.32103. Epub 2012 Oct 17.
• [15] Aberrant methylation status of known methylation-sensitive CpG islands in gastrointestinal stromal tumors without any correlation to the state of c-kit and PDGFRA gene mutations and their malignancy.Cancer Sci. 2008 Feb;99(2):253-9. doi: 10.1111/j.1349-7006.2007.00682.x.
• [16] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [17] Molecular features of colorectal hyperplastic polyps and sessile serrated adenoma/polyps from Korea.Am J Surg Pathol. 2011 Sep;35(9):1274-86. doi: 10.1097/PAS.0b013e318224cd2e.
• [18] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [19] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [20] Identification of vitamin D3 target genes in human breast cancer tissue. J Steroid Biochem Mol Biol. 2016 Nov;164:90-97.
• [21] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [22] 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.
• [23] 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.
• [24] Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 2013 Mar;3(3):308-23.
• [25] Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations. Int J Cancer. 2006 Apr 1;118(7):1699-712. doi: 10.1002/ijc.21570.