Details of Drug Off-Target (DOT)

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

• DOT Name: Beta-soluble NSF attachment protein (NAPB)
• Synonyms: SNAP-beta; N-ethylmaleimide-sensitive factor attachment protein beta
• Gene Name: NAPB
• Related Disease:
  Developmental and epileptic encephalopathy 107
  Epilepsy
  Sjogren syndrome
• UniProt ID: SNAB_HUMAN
• Pfam ID: PF14938
• Sequence:
  MDNAGKEREAVQLMAEAEKRVKASHSFLRGLFGGNTRIEEACEMYTRAANMFKMAKNWSA
  AGNAFCQAAKLHMQLQSKHDSATSFVDAGNAYKKADPQEAINCLNAAIDIYTDMGRFTIA
  AKHHITIAEIYETELVDIEKAIAHYEQSADYYKGEESNSSANKCLLKVAAYAAQLEQYQK
  AIEIYEQVGANTMDNPLLKYSAKDYFFKAALCHFIVDELNAKLALEKYEEMFPAFTDSRE
  CKLLKKLLEAHEEQNSEAYTEAVKEFDSISRLDQWLTTMLLRIKKSIQGDGEGDGDLK
• Function: Required for vesicular transport between the endoplasmic reticulum and the Golgi apparatus.
• Reactome Pathway:
  COPI-mediated anterograde transport (R-HSA-6807878)
  COPI-dependent Golgi-to-ER retrograde traffic (R-HSA-6811434)
  Intra-Golgi traffic (R-HSA-6811438)
  Retrograde transport at the Trans-Golgi-Network (R-HSA-6811440)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy 107	DIS2YWQG	Strong	Autosomal recessive	[1]
Epilepsy	DISBB28L	Strong	Genetic Variation	[1]
Sjogren syndrome	DISUBX7H	Strong	Genetic Variation	[2]

5 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 Beta-soluble NSF attachment protein (NAPB).	[3]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Beta-soluble NSF attachment protein (NAPB).	[4]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Beta-soluble NSF attachment protein (NAPB).	[5]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Beta-soluble NSF attachment protein (NAPB).	[6]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Beta-soluble NSF attachment protein (NAPB).	[7]

References

• [1] NAPB - a novel SNARE-associated protein for early-onset epileptic encephalopathy. Clin Genet. 2016 Feb;89(2):E1-3. doi: 10.1111/cge.12648. Epub 2015 Aug 28.
• [2] Variants at potential loci associated with Sjogren's syndrome in Koreans: A genetic association study.Clin Immunol. 2019 Oct;207:79-86. doi: 10.1016/j.clim.2019.07.010. Epub 2019 Jul 23.
• [3] 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.
• [4] 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.
• [5] 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.
• [6] 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.
• [7] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.