Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7AZBZJ)

• DOT Name: Dual oxidase maturation factor 2 (DUOXA2)
• Synonyms: Dual oxidase activator 2
• Gene Name: DUOXA2
• Related Disease:
  Goiter
  Colitis
  Congenital hypothyroidism
  Familial thyroid dyshormonogenesis 1
  Hypothyroidism
  Thyroid dyshormonogenesis 5
  Ulcerative colitis
  Familial thyroid dyshormonogenesis
  Lung cancer
  Lung carcinoma
• UniProt ID: DOXA2_HUMAN
• Pfam ID: PF10204
• Sequence:
  MTLWNGVLPFYPQPRHAAGFSVPLLIVILVFLALAASFLLILPGIRGHSRWFWLVRVLLS
  LFIGAEIVAVHFSAEWFVGTVNTNTSYKAFSAARVTARVRLLVGLEGINITLTGTPVHQL
  NETIDYNEQFTWRLKENYAAEYANALEKGLPDPVLYLAEKFTPSSPCGLYHQYHLAGHYA
  SATLWVAFCFWLLSNVLLSTPAPLYGGLALLTTGAFALFGVFALASISSVPLCPLRLGSS
  ALTTQYGAAFWVTLATGVLCLFLGGAVVSLQYVRPSALRTLLDQSAKDCSQERGGSPLIL
  GDPLHKQAALPDLKCITTNL
• Function: Required for the maturation and the transport from the endoplasmic reticulum to the plasma membrane of functional DUOX2. May play a role in thyroid hormone synthesis.
• Tissue Specificity: Specifically expressed in thyroid. Also detected in salivary glands.
• KEGG Pathway: Thyroid hormone synthesis (hsa04918)

Molecular Interaction Atlas (MIA) of This DOT

10 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Goiter	DISLCGI6	Definitive	Genetic Variation	[1]
Colitis	DISAF7DD	Strong	Altered Expression	[2]
Congenital hypothyroidism	DISL5XVU	Strong	Biomarker	[3]
Familial thyroid dyshormonogenesis 1	DISAXKZN	Strong	GermlineCausalMutation	[4]
Hypothyroidism	DISR0H6D	Strong	Genetic Variation	[1]
Thyroid dyshormonogenesis 5	DISMIKWD	Strong	Autosomal recessive	[5]
Ulcerative colitis	DIS8K27O	Strong	Biomarker	[6]
Familial thyroid dyshormonogenesis	DISALTXN	Supportive	Autosomal recessive	[7]
Lung cancer	DISCM4YA	Limited	Altered Expression	[8]
Lung carcinoma	DISTR26C	Limited	Altered Expression	[8]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Methotrexate	DM2TEOL	Approved	Methotrexate decreases the expression of Dual oxidase maturation factor 2 (DUOXA2).	[9]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Dual oxidase maturation factor 2 (DUOXA2).	[11]

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 decreases the methylation of Dual oxidase maturation factor 2 (DUOXA2).	[10]

References

• [1] A novel missense mutation (I26M) in DUOXA2 causing congenital goiter hypothyroidism impairs NADPH oxidase activity but not protein expression.J Clin Endocrinol Metab. 2015 Apr;100(4):1225-9. doi: 10.1210/jc.2014-3964. Epub 2015 Feb 12.
• [2] Separation of Dual Oxidase 2 and Lactoperoxidase Expression in Intestinal Crypts and Species Differences May Limit Hydrogen Peroxide Scavenging During Mucosal Healing in Mice and Humans.Inflamm Bowel Dis. 2017 Dec 19;24(1):136-148. doi: 10.1093/ibd/izx024.
• [3] Identification of Two Missense Mutations in DUOX1 (p.R1307Q) and DUOXA1 (p.R56W) That Can Cause Congenital Hypothyroidism Through Impairing H(2)O(2) Generation.Front Endocrinol (Lausanne). 2019 Aug 2;10:526. doi: 10.3389/fendo.2019.00526. eCollection 2019.
• [4] Genetic causes of congenital hypothyroidism due to dyshormonogenesis.Curr Opin Pediatr. 2011 Aug;23(4):421-8. doi: 10.1097/MOP.0b013e32834726a4.
• [5] Biallelic inactivation of the dual oxidase maturation factor 2 (DUOXA2) gene as a novel cause of congenital hypothyroidism. J Clin Endocrinol Metab. 2008 Feb;93(2):605-10. doi: 10.1210/jc.2007-2020. Epub 2007 Nov 27.
• [6] DUOX2 and DUOXA2 form the predominant enzyme system capable of producing the reactive oxygen species H2O2 in active ulcerative colitis and are modulated by 5-aminosalicylic acid.Inflamm Bowel Dis. 2014 Mar;20(3):514-24. doi: 10.1097/01.MIB.0000442012.45038.0e.
• [7] Congenital hypothyroidism. Orphanet J Rare Dis. 2010 Jun 10;5:17. doi: 10.1186/1750-1172-5-17.
• [8] Silencing of DUOX NADPH oxidases by promoter hypermethylation in lung cancer.Cancer Res. 2008 Feb 15;68(4):1037-45. doi: 10.1158/0008-5472.CAN-07-5782.
• [9] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [10] 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.
• [11] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.