Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT5VS65E)

• DOT Name: Rabphilin-3A (RPH3A)
• Synonyms: Exophilin-1
• Gene Name: RPH3A
• Related Disease: Congenital myasthenic syndrome
• UniProt ID: RP3A_HUMAN
• Pfam ID: PF00168 ; PF02318
• Sequence:
  MTDTVFSNSSNRWMYPSDRPLQSNDKEQLQAGWSVHPGGQPDRQRKQEELTDEEKEIINR
  VIARAEKMEEMEQERIGRLVDRLENMRKNVAGDGVNRCILCGEQLGMLGSACVVCEDCKK
  NVCTKCGVETNNRLHSVWLCKICIEQREVWKRSGAWFFKGFPKQVLPQPMPIKKTKPQQP
  VSEPAAPEQPAPEPKHPARAPARGDSEDRRGPGQKTGPDPASAPGRGNYGPPVRRASEAR
  MSSSSRDSESWDHSGGAGDSSRSPAGLRRANSVQASRPAPGSVQSPAPPQPGQPGTPGGS
  RPGPGPAGRFPDQKPEVAPSDPGTTAPPREERTGGVGGYPAVGAREDRMSHPSGPYSQAS
  AAAPQPAAARQPPPPEEEEEEANSYDSDEATTLGALEFSLLYDQDNSSLQCTIIKAKGLK
  PMDSNGLADPYVKLHLLPGASKSNKLRTKTLRNTRNPIWNETLVYHGITDEDMQRKTLRI
  SVCDEDKFGHNEFIGETRFSLKKLKPNQRKNFNICLERVIPMKRAGTTGSARGMALYEEE
  QVERVGDIEERGKILVSLMYSTQQGGLIVGIIRCVHLAAMDANGYSDPFVKLWLKPDMGK
  KAKHKTQIKKKTLNPEFNEEFFYDIKHSDLAKKSLDISVWDYDIGKSNDYIGGCQLGISA
  KGERLKHWYECLKNKDKKIERWHQLQNENHVSSD
• Function: Plays an essential role in docking and fusion steps of regulated exocytosis. At the presynaptic level, RPH3A is recruited by RAB3A to the synaptic vesicle membrane in a GTP-dependent manner where it modulates synaptic vesicle trafficking and calcium-triggered neurotransmitter release. In the post-synaptic compartment, forms a ternary complex with GRIN2A and DLG4 and regulates NMDA receptor stability. Also plays a role in the exocytosis of arginine vasopressin hormone.

Molecular Interaction Atlas (MIA) of This DOT

1 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Congenital myasthenic syndrome	DISJLG2T	Limited	Autosomal recessive	[1]

This DOT Affected the Drug Response of 1 Drug(s)

Drug Name	Drug ID	Highest Status	Interaction	REF
Ethanol	DMDRQZU	Approved	Rabphilin-3A (RPH3A) affects the response to substance of Ethanol.	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Rabphilin-3A (RPH3A).	[2]
Malathion	DMXZ84M	Approved	Malathion decreases the expression of Rabphilin-3A (RPH3A).	[3]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Rabphilin-3A (RPH3A).	[5]

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 Rabphilin-3A (RPH3A).	[4]

References

• [1] Classification of Genes: Standardized Clinical Validity Assessment of Gene-Disease Associations Aids Diagnostic Exome Analysis and Reclassifications. Hum Mutat. 2017 May;38(5):600-608. doi: 10.1002/humu.23183. Epub 2017 Feb 13.
• [2] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [3] Exposure to Insecticides Modifies Gene Expression and DNA Methylation in Hematopoietic Tissues In Vitro. Int J Mol Sci. 2023 Mar 26;24(7):6259. doi: 10.3390/ijms24076259.
• [4] 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.
• [5] Comparison of transcriptome expression alterations by chronic exposure to low-dose bisphenol A in different subtypes of breast cancer cells. Toxicol Appl Pharmacol. 2019 Dec 15;385:114814. doi: 10.1016/j.taap.2019.114814. Epub 2019 Nov 9.
• [6] The potential effects of HECTD4 variants on fasting glucose and triglyceride levels in relation to prevalence of type 2 diabetes based on alcohol intake. Arch Toxicol. 2022 Sep;96(9):2487-2499. doi: 10.1007/s00204-022-03325-y. Epub 2022 Jun 17.