Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTH49JRW)

• DOT Name: Adaptin ear-binding coat-associated protein 1 (NECAP1)
• Synonyms: NECAP endocytosis-associated protein 1; NECAP-1
• Gene Name: NECAP1
• Related Disease:
  Developmental and epileptic encephalopathy, 21
  Infantile epileptic-dyskinetic encephalopathy
  Infantile spasm
  Undetermined early-onset epileptic encephalopathy
• UniProt ID: NECP1_HUMAN
• PDB ID: 6RH5; 6RH6
• Pfam ID: PF07933
• Sequence:
  MATELEYESVLCVKPDVSVYRIPPRASNRGYRASDWKLDQPDWTGRLRITSKGKTAYIKL
  EDKVSGELFAQAPVEQYPGIAVETVTDSSRYFVIRIQDGTGRSAFIGIGFTDRGDAFDFN
  VSLQDHFKWVKQESEISKESQEMDARPKLDLGFKEGQTIKLCIGNITNKKGGASKPRTAR
  GGGLSLLPPPPGGKVTIPPPSSSVAISNHVTPPPIPKSNHGGSDADILLDLDSPAPVTTP
  APTPVSVSNDLWGDFSTASSSVPNQAPQPSNWVQF
• Function: Involved in endocytosis.
• Reactome Pathway:
  Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825)
  Clathrin-mediated endocytosis (R-HSA-8856828)
  Golgi Associated Vesicle Biogenesis (R-HSA-432722)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Developmental and epileptic encephalopathy, 21	DISA3UBY	Strong	Autosomal recessive	[1]
Infantile epileptic-dyskinetic encephalopathy	DISD2ZNC	Strong	Genetic Variation	[2]
Infantile spasm	DISZSKDG	Moderate	Autosomal recessive	[3]
Undetermined early-onset epileptic encephalopathy	DISISEI2	Supportive	Autosomal dominant	[1]

8 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 Adaptin ear-binding coat-associated protein 1 (NECAP1).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[6]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[7]
Hydrogen peroxide	DM1NG5W	Approved	Hydrogen peroxide affects the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[8]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[8]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[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 affects the methylation of Adaptin ear-binding coat-associated protein 1 (NECAP1).	[9]

References

• [1] NECAP1 loss of function leads to a severe infantile epileptic encephalopathy. J Med Genet. 2014 Apr;51(4):224-8. doi: 10.1136/jmedgenet-2013-102030. Epub 2014 Jan 7.
• [2] A novel homozygous truncating variant of NECAP1 in early infantile epileptic encephalopathy: the second case report of EIEE21.J Hum Genet. 2019 Apr;64(4):347-350. doi: 10.1038/s10038-018-0556-2. Epub 2019 Jan 9.
• [3] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [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] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [8] Time series analysis of oxidative stress response patterns in HepG2: a toxicogenomics approach. Toxicology. 2013 Apr 5;306:24-34.
• [9] 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.
• [10] 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.
• [11] Alternatives for the worse: Molecular insights into adverse effects of bisphenol a and substitutes during human adipocyte differentiation. Environ Int. 2021 Nov;156:106730. doi: 10.1016/j.envint.2021.106730. Epub 2021 Jun 27.