Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8QI4GF)

• DOT Name: Nucleosome assembly protein 1-like 2 (NAP1L2)
• Synonyms: Brain-specific protein, X-linked
• Gene Name: NAP1L2
• Related Disease:
  Acne vulgaris
  Atopic dermatitis
  Colorectal carcinoma
  Neural tube defect
• UniProt ID: NP1L2_HUMAN
• Pfam ID: PF00956
• Sequence:
  MAESENRKELSESSQEEAGNQIMVEGLGEHLERGEDAAAGLGDDGKCGEEAAAGLGEEGE
  NGEDTAAGSGEDGKKGGDTDEDSEADRPKGLIGYVLDTDFVESLPVKVKYRVLALKKLQT
  RAANLESKFLREFHDIERKFAEMYQPLLEKRRQIINAIYEPTEEECEYKSDSEDCDDEEM
  CHEEMYGNEEGMVHEYVDEDDGYEDYYYDYAVEEEEEEEEEDDIEATGEENKEEEDPKGI
  PDFWLTVLKNVDTLTPLIKKYDEPILKLLTDIKVKLSDPGEPLSFTLEFHFKPNEYFKNE
  LLTKTYVLKSKLAYYDPHPYRGTAIEYSTGCEIDWNEGKNVTLKTIKKKQKHRIWGTIRT
  VTEDFPKDSFFNFFSPHGITSNGRDGNDDFLLGHNLRTYIIPRSVLFFSGDALESQQEGV
  VREVNDAIYDKIIYDNWMAAIEEVKACCKNLEALVEDIDR
• Function: Acidic protein which may be involved in interactions with other proteins or DNA.

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Acne vulgaris	DISKW8PI	Definitive	Biomarker	[1]
Atopic dermatitis	DISTCP41	Strong	Biomarker	[2]
Colorectal carcinoma	DIS5PYL0	Strong	Biomarker	[3]
Neural tube defect	DIS5J95E	Disputed	Altered Expression	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[5]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate affects the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[8]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[9]
Bortezomib	DMNO38U	Approved	Bortezomib increases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[10]
Urethane	DM7NSI0	Phase 4	Urethane decreases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[11]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[12]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Nucleosome assembly protein 1-like 2 (NAP1L2).	[13]

References

• [1] Treating Acne With Topical Antibiotics: Current Obstacles and the Introduction of Topical Minocycline as a New Treatment Option.J Drugs Dermatol. 2019 Mar 1;18(3):240-244.
• [2] Identification of candidate genes in atopic dermatitis based on bioinformatic methods.Int J Dermatol. 2016 Jul;55(7):791-800. doi: 10.1111/ijd.13291. Epub 2016 Mar 9.
• [3] Role of extracellular LncRNA-SNHG14/miRNA-3940-5p/NAP12 mRNA in colorectal cancer.Arch Physiol Biochem. 2021 Dec;127(6):479-485. doi: 10.1080/13813455.2019.1650070. Epub 2019 Aug 9.
• [4] SNPs in the CpG island of NAP1L2: a possible link between DNA methylation and neural tube defects?.Am J Med Genet. 2002 Jul 1;110(3):208-14. doi: 10.1002/ajmg.10453.
• [5] 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.
• [6] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [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] 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.
• [11] Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
• [12] Benzo[a]pyrene-induced changes in microRNA-mRNA networks. Chem Res Toxicol. 2012 Apr 16;25(4):838-49.
• [13] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.