Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT9ZOFN9)

• DOT Name: Deoxyribonuclease-1-like 1 (DNASE1L1)
• Synonyms: EC 3.1.21.-; DNase X; Deoxyribonuclease I-like 1; DNase I-like 1; Muscle-specific DNase I-like; XIB
• Gene Name: DNASE1L1
• Related Disease:
  Head and neck cancer
  Head and neck carcinoma
  Advanced cancer
  Neoplasm
  Prostate cancer
  Prostate carcinoma
  Schizophrenia
• UniProt ID: DNSL1_HUMAN
• EC Number: 3.1.21.-
• Pfam ID: PF03372
• Sequence:
  MHYPTALLFLILANGAQAFRICAFNAQRLTLAKVAREQVMDTLVRILARCDIMVLQEVVD
  SSGSAIPLLLRELNRFDGSGPYSTLSSPQLGRSTYMETYVYFYRSHKTQVLSSYVYNDED
  DVFAREPFVAQFSLPSNVLPSLVLVPLHTTPKAVEKELNALYDVFLEVSQHWQSKDVILL
  GDFNADCASLTKKRLDKLELRTEPGFHWVIADGEDTTVRASTHCTYDRVVLHGERCRSLL
  HTAAAFDFPTSFQLTEEEALNISDHYPVEVELKLSQAHSVQPLSLTVLLLLSLLSPQLCP
  AA
• Tissue Specificity: Highest levels in skeletal and cardiac muscles. Detectable in all other tissues tested except brain.
• Reactome Pathway: Neutrophil degranulation (R-HSA-6798695)

Molecular Interaction Atlas (MIA) of This DOT

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Head and neck cancer	DISBPSQZ	Strong	Biomarker	[1]
Head and neck carcinoma	DISOU1DS	Strong	Biomarker	[1]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[2]
Neoplasm	DISZKGEW	Limited	Biomarker	[2]
Prostate cancer	DISF190Y	Limited	Biomarker	[2]
Prostate carcinoma	DISMJPLE	Limited	Biomarker	[2]
Schizophrenia	DISSRV2N	Limited	Altered Expression	[3]

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-1-like 1 (DNASE1L1).	[4]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the methylation of Deoxyribonuclease-1-like 1 (DNASE1L1).	[13]

9 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-1-like 1 (DNASE1L1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[9]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[10]
Arsenic trioxide	DM61TA4	Approved	Arsenic trioxide increases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[11]
Zoledronate	DMIXC7G	Approved	Zoledronate increases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[12]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of Deoxyribonuclease-1-like 1 (DNASE1L1).	[14]

References

• [1] Systematic analysis of survival-associated alternative splicing signatures uncovers prognostic predictors for head and neck cancer.J Cell Physiol. 2019 Sep;234(9):15836-15846. doi: 10.1002/jcp.28241. Epub 2019 Feb 10.
• [2] Effect of radical prostatectomy on levels of cancer related epitopes in circulating macrophages of patients with clinically localized prostate cancer.Prostate. 2017 Sep;77(12):1251-1258. doi: 10.1002/pros.23384. Epub 2017 Jul 20.
• [3] Multivariate eQTL mapping uncovers functional variation on the X-chromosome associated with complex disease traits.Hum Genet. 2016 Jul;135(7):827-39. doi: 10.1007/s00439-016-1674-6. Epub 2016 May 7.
• [4] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Transcriptional and Metabolic Dissection of ATRA-Induced Granulocytic Differentiation in NB4 Acute Promyelocytic Leukemia Cells. Cells. 2020 Nov 5;9(11):2423. doi: 10.3390/cells9112423.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [10] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [11] Essential role of cell cycle regulatory genes p21 and p27 expression in inhibition of breast cancer cells by arsenic trioxide. Med Oncol. 2011 Dec;28(4):1225-54.
• [12] The proapoptotic effect of zoledronic acid is independent of either the bone microenvironment or the intrinsic resistance to bortezomib of myeloma cells and is enhanced by the combination with arsenic trioxide. Exp Hematol. 2011 Jan;39(1):55-65.
• [13] 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.
• [14] 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.