Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7NFEO6)

• DOT Name: D-amino acid oxidase regulator (DAOA)
• Synonyms: Protein G72
• Gene Name: DAOA
• Related Disease:
  Autism spectrum disorder
  Behcet disease
  Bipolar I disorder
  Depression
  Mental disorder
  Panic disorder
  Psychotic disorder
• UniProt ID: DAOA_HUMAN
• Pfam ID: PF15199
• Sequence:
  MLEKLMGADSLQLFRSRYTLGKIYFIGFQRSILLSKSENSLNSIAKETEEGRETVTRKEG
  WKRRHEDGYLEMAQRHLQRSLCPWVSYLPQPYAELEEVSSHVGKVFMARNYEFLAYEASK
  DRRQPLERMWTCNYNQQKDQSCNHKEITSTKAE
• Function: May suppress DAO (D-amino acid oxidase) and SOD1 activity and promote their degradation. Has conversely also been suggested to function as a DAO activator. May stimulate the degradation of DDO (D-aspartate oxidase). May play a role in mitochondrial fission.
• Tissue Specificity: Expressed in the amygdala and in astrocytes of the cortex (at protein level) . Expressed in the caudate nucleus, spinal cord and testis .

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autism spectrum disorder	DISXK8NV	Strong	Genetic Variation	[1]
Behcet disease	DISSYMBS	Strong	Biomarker	[2]
Bipolar I disorder	DISD09EH	Strong	Genetic Variation	[3]
Depression	DIS3XJ69	Strong	Genetic Variation	[4]
Mental disorder	DIS3J5R8	Strong	Biomarker	[5]
Panic disorder	DISD3VNY	Strong	Genetic Variation	[6]
Psychotic disorder	DIS4UQOT	Strong	Genetic Variation	[7]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of D-amino acid oxidase regulator (DAOA).	[8]

2 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 D-amino acid oxidase regulator (DAOA).	[9]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the methylation of D-amino acid oxidase regulator (DAOA).	[10]

References

• [1] Association of the DAO and DAOA gene polymorphisms with autism spectrum disorders in boys in Korea: a preliminary study.Psychiatry Res. 2007 Oct 31;153(2):179-82. doi: 10.1016/j.psychres.2007.02.007. Epub 2007 Jul 16.
• [2] DAOA variants on diagnosis and response to treatment in patients with major depressive disorder and bipolar disorder.J Int Med Res. 2012;40(1):258-65. doi: 10.1177/147323001204000126.
• [3] Cognitive manic symptoms in bipolar disorder associated with polymorphisms in the DAOA and COMT genes.PLoS One. 2013 Jul 5;8(7):e67450. doi: 10.1371/journal.pone.0067450. Print 2013.
• [4] Association between DAOA gene polymorphisms and the risk of schizophrenia, bipolar disorder and depressive disorder.Prog Neuropsychopharmacol Biol Psychiatry. 2014 Jun 3;51:89-98. doi: 10.1016/j.pnpbp.2014.01.007. Epub 2014 Jan 19.
• [5] Expression of the G72/G30 gene in transgenic mice induces behavioral changes.Mol Psychiatry. 2014 Feb;19(2):175-83. doi: 10.1038/mp.2012.185. Epub 2013 Jan 22.
• [6] Investigation of the DAOA/G30 locus in panic disorder.Mol Psychiatry. 2005 May;10(5):428-9. doi: 10.1038/sj.mp.4001598.
• [7] Influence of DAOA and RGS4 genes on the risk for psychotic disorders and their associated executive dysfunctions: A family-based study.Eur Psychiatry. 2016 Feb;32:42-7. doi: 10.1016/j.eurpsy.2015.11.002. Epub 2016 Jan 21.
• [8] 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.
• [9] 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.
• [10] DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.