Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT2N7NQR)

• DOT Name: G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2)
• Synonyms: GASP-2
• Gene Name: ARMCX5-GPRASP2
• Related Disease:
  Alzheimer disease
  X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome
  Advanced cancer
• UniProt ID: GASP2_HUMAN
• Pfam ID: PF04826
• Sequence:
  MTGAEIEPSAQAKPEKKAGEEVIAGPERENDVPLVVRPKVRTQATTGARPKTETKSVPAA
  RPKTEAQAMSGARPKTEVQVMGGARPKTEAQGITGARPKTDARAVGGARSKTDAKAIPGA
  RPKDEAQAWAQSEFGTEAVSQAEGVSQTNAVAWPLATAESGSVTKSKGLSMDRELVNVDA
  ETFPGTQGQKGIQPWFGPGEETNMGSWCYSRPRAREEASNESGFWSADETSTASSFWTGE
  ETSVRSWPREESNTRSRHRAKHQTNPRSRPRSKQEAYVDSWSGSEDEASNPFSFWVGENT
  NNLFRPRVREEANIRSKLRTNREDCFESESEDEFYKQSWVLPGEEANSRFRHRDKEDPNT
  ALKLRAQKDVDSDRVKQEPRFEEEVIIGSWFWAEKEASLEGGASAICESEPGTEEGAIGG
  SAYWAEEKSSLGAVAREEAKPESEEEAIFGSWFWDRDEACFDLNPCPVYKVSDRFRDAAE
  ELNASSRPQTWDEVTVEFKPGLFHGVGFRSTSPFGIPEEASEMLEAKPKNLELSPEGEEQ
  ESLLQPDQPSPEFTFQYDPSYRSVREIREHLRARESAESESWSCSCIQCELKIGSEEFEE
  FLLLMDKIRDPFIHEISKIAMGMRSASQFTRDFIRDSGVVSLIETLLNYPSSRVRTSFLE
  NMIHMAPPYPNLNMIETFICQVCEETLAHSVDSLEQLTGIRMLRHLTMTIDYHTLIANYM
  SGFLSLLTTANARTKFHVLKMLLNLSENPAVAKKLFSAKALSIFVGLFNIEETNDNIQIV
  IKMFQNISNIIKSGKMSLIDDDFSLEPLISAFREFEELAKQLQAQIDNQNDPEVGQQS
• Function: May play a role in regulation of a variety of G-protein coupled receptors.
• Tissue Specificity: Expressed in the brain.

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
X-linked external auditory canal atresia-dilated internal auditory canal-facial dysmorphism syndrome	DISIT57H	Supportive	X-linked	[2]
Advanced cancer	DISAT1Z9	Limited	Biomarker	[3]

7 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 G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[4]
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[5]
Cisplatin	DMRHGI9	Approved	Cisplatin decreases the expression of G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[6]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[7]
Folic acid	DMEMBJC	Approved	Folic acid decreases the expression of G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[8]
Urethane	DM7NSI0	Phase 4	Urethane increases the expression of G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A decreases the expression of G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[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 G-protein coupled receptor-associated sorting protein 2 (ARMCX5-GPRASP2).	[10]

References

• [1] P60TRP interferes with the GPCR/secretase pathway to mediate neuronal survival and synaptogenesis.J Cell Mol Med. 2011 Nov;15(11):2462-77. doi: 10.1111/j.1582-4934.2010.01248.x.
• [2] GPRASP2, a novel causative gene mutated in an X-linked recessive syndromic hearing loss. J Med Genet. 2017 Jun;54(6):426-430. doi: 10.1136/jmedgenet-2016-104320. Epub 2017 Jan 17.
• [3] Glutamate E15 and E171 are Hotspots in p60TRP-Related Cancer.Cancer Invest. 2016;34(2):64-9. doi: 10.3109/07357907.2015.1088949. Epub 2016 Feb 6.
• [4] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [5] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [6] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [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] Folic acid supplementation dysregulates gene expression in lymphoblastoid cells--implications in nutrition. Biochem Biophys Res Commun. 2011 Sep 9;412(4):688-92. doi: 10.1016/j.bbrc.2011.08.027. Epub 2011 Aug 16.
• [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] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.