Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTG3B2QL)

• DOT Name: Protein NipSnap homolog 2 (NIPSNAP2)
• Synonyms: NipSnap2; Glioblastoma-amplified sequence
• Gene Name: NIPSNAP2
• Related Disease: Non-small-cell lung cancer
• UniProt ID: NIPS2_HUMAN
• Pfam ID: PF07978
• Sequence:
  MAARVLRARGAAWAGGLLQRAAPCSLLPRLRTWTSSSNRSREDSWLKSLFVRKVDPRKDA
  HSNLLAKKETSNLYKLQFHNVKPECLEAYNKICQEVLPKIHEDKHYPCTLVGTWNTWYGE
  QDQAVHLWRYEGGYPALTEVMNKLRENKEFLEFRKARSDMLLSRKNQLLLEFSFWNEPVP
  RSGPNIYELRSYQLRPGTMIEWGNYWARAIRFRQDGNEAVGGFFSQIGQLYMVHHLWAYR
  DLQTREDIRNAAWHKHGWEELVYYTVPLIQEMESRIMIPLKTSPLQ
• Function: May act as a positive regulator of L-type calcium channels.
• Tissue Specificity: Widely expressed. Most abundant in heart and skeletal muscle.
• Reactome Pathway:
  RHOJ GTPase cycle (R-HSA-9013409)
  RHOH GTPase cycle (R-HSA-9013407)

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Non-small-cell lung cancer	DIS5Y6R9	Strong	Genetic Variation	[1]

9 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 Protein NipSnap homolog 2 (NIPSNAP2).	[2]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[3]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[5]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide increases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[7]
Sodium lauryl sulfate	DMLJ634	Approved	Sodium lauryl sulfate decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[9]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Protein NipSnap homolog 2 (NIPSNAP2).	[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 increases the methylation of Protein NipSnap homolog 2 (NIPSNAP2).	[10]

References

• [1] Intronic variant of EGFR is associated with GBAS expression and survival outcome of early-stage non-small cell lung cancer.Thorac Cancer. 2018 Aug;9(8):916-923. doi: 10.1111/1759-7714.12757. Epub 2018 May 28.
• [2] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [3] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [4] 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.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin, benefiting for COVID-19 treatment. J Cell Physiol. 2021 Apr;236(4):2959-2975. doi: 10.1002/jcp.30055. Epub 2020 Sep 22.
• [7] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [8] CXCL14 downregulation in human keratinocytes is a potential biomarker for a novel in vitro skin sensitization test. Toxicol Appl Pharmacol. 2020 Jan 1;386:114828. doi: 10.1016/j.taap.2019.114828. Epub 2019 Nov 14.
• [9] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [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] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.