Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT6RC1BL)

• DOT Name: Deoxyribonuclease-2-alpha (DNASE2)
• Synonyms: EC 3.1.22.1; Acid DNase; Deoxyribonuclease II alpha; DNase II alpha; Lysosomal DNase II; R31240_2
• Gene Name: DNASE2
• Related Disease:
  Nephropathy
  Advanced cancer
  Anemia
  Autoimmune disease
  Autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency
  Bacterial infection
  Fatty liver disease
  Hepatocellular carcinoma
  Hypothyroidism
  Non-small-cell lung cancer
  Rheumatoid arthritis
  Systemic lupus erythematosus
  Trichinellosis
• UniProt ID: DNS2A_HUMAN
• EC Number: 3.1.22.1
• Pfam ID: PF03265
• Sequence:
  MIPLLLAALLCVPAGALTCYGDSGQPVDWFVVYKLPALRGSGEAAQRGLQYKYLDESSGG
  WRDGRALINSPEGAVGRSLQPLYRSNTSQLAFLLYNDQPPQPSKAQDSSMRGHTKGVLLL
  DHDGGFWLVHSVPNFPPPASSAAYSWPHSACTYGQTLLCVSFPFAQFSKMGKQLTYTYPW
  VYNYQLEGIFAQEFPDLENVVKGHHVSQEPWNSSITLTSQAGAVFQSFAKFSKFGDDLYS
  GWLAAALGTNLQVQFWHKTVGILPSNCSDIWQVLNVNQIAFPGPAGPSFNSTEDHSKWCV
  SPKGPWTCVGDMNRNQGEEQRGGGTLCAQLPALWKAFQPLVKNYQPCNGMARKPSRAYKI
• Function: Hydrolyzes DNA under acidic conditions with a preference for double-stranded DNA. Plays a major role in the clearance of nucleic acids generated through apoptosis, hence preventing autoinflammation. Necessary for proper fetal development and for definitive erythropoiesis in fetal liver and bone marrow, where it degrades nuclear DNA expelled from erythroid precursor cells.
• Tissue Specificity: Expressed in monocytes/macrophages (at protein level).
• KEGG Pathway:
  Lysosome (hsa04142)
  Cytosolic D.-sensing pathway (hsa04623)
• Reactome Pathway: Lysosome Vesicle Biogenesis (R-HSA-432720)

Molecular Interaction Atlas (MIA) of This DOT

13 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Nephropathy	DISXWP4P	Definitive	Genetic Variation	[1]
Advanced cancer	DISAT1Z9	Strong	Biomarker	[2]
Anemia	DISTVL0C	Strong	Biomarker	[3]
Autoimmune disease	DISORMTM	Strong	Biomarker	[4]
Autoinflammatory-pancytopenia syndrome due to DNASE2 deficiency	DISRSAB9	Strong	Autosomal recessive	[5]
Bacterial infection	DIS5QJ9S	Strong	Genetic Variation	[6]
Fatty liver disease	DIS485QZ	Strong	Biomarker	[7]
Hepatocellular carcinoma	DIS0J828	Strong	Genetic Variation	[8]
Hypothyroidism	DISR0H6D	Strong	Altered Expression	[9]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[10]
Rheumatoid arthritis	DISTSB4J	Strong	Altered Expression	[11]
Systemic lupus erythematosus	DISI1SZ7	Strong	Biomarker	[12]
Trichinellosis	DISUR2ZW	Limited	Biomarker	[13]

2 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Deoxyribonuclease-2-alpha (DNASE2).	[14]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Deoxyribonuclease-2-alpha (DNASE2).	[21]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[15]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[16]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[17]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[18]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[19]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[20]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[22]
Decitabine	DMQL8XJ	Approved	Decitabine affects the expression of Deoxyribonuclease-2-alpha (DNASE2).	[23]
Nicotine	DMWX5CO	Approved	Nicotine decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[24]
Menthol	DMG2KW7	Approved	Menthol decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[25]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[26]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[24]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[27]
THAPSIGARGIN	DMDMQIE	Preclinical	THAPSIGARGIN increases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[28]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[29]
PP-242	DM2348V	Investigative	PP-242 decreases the expression of Deoxyribonuclease-2-alpha (DNASE2).	[30]

References

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