Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT0ZRV5C)

• DOT Name: Trafficking protein particle complex subunit 6A (TRAPPC6A)
• Synonyms: TRAPP complex subunit 6A
• Gene Name: TRAPPC6A
• Related Disease:
  Complex neurodevelopmental disorder
  Intellectual disability
• UniProt ID: TPC6A_HUMAN
• PDB ID: 2C0J; 2J3T
• Pfam ID: PF04051
• Sequence:
  MADTVLFEFLHTEMVAELWAHDPDPGPGGQKMSLSVLEGMGFRVGQALGERLPRETLAFR
  EELDVLKFLCKDLWVAVFQKQMDSLRTNHQGTYVLQDNSFPLLLPMASGLQYLEEAPKFL
  AFTCGLLRGALYTLGIESVVTASVAALPVCKFQVVIPKS
• Function: May play a role in vesicular transport during the biogenesis of melanosomes.
• Reactome Pathway:
  RAB GEFs exchange GTP for GDP on RABs (R-HSA-8876198)
  COPII-mediated vesicle transport (R-HSA-204005)

Molecular Interaction Atlas (MIA) of This DOT

2 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Complex neurodevelopmental disorder	DISB9AFI	Limited	Autosomal recessive	[1]
Intellectual disability	DISMBNXP	Limited	Biomarker	[2]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[3]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin decreases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[4]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[5]
Estradiol	DMUNTE3	Approved	Estradiol decreases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[6]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[8]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[9]
Aspirin	DM672AH	Approved	Aspirin increases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[10]
Testosterone enanthate	DMB6871	Approved	Testosterone enanthate affects the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[11]
GSK2110183	DMZHB37	Phase 2	GSK2110183 increases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[13]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A increases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[14]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Trafficking protein particle complex subunit 6A (TRAPPC6A).	[15]

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] A missense mutation in TRAPPC6A leads to build-up of the protein, in patients with a neurodevelopmental syndrome and dysmorphic features. Sci Rep. 2018 Feb 1;8(1):2053. doi: 10.1038/s41598-018-20658-w.
• [3] 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.
• [4] Integrating multiple omics to unravel mechanisms of Cyclosporin A induced hepatotoxicity in vitro. Toxicol In Vitro. 2015 Apr;29(3):489-501.
• [5] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [6] Genistein and bisphenol A exposure cause estrogen receptor 1 to bind thousands of sites in a cell type-specific manner. Genome Res. 2012 Nov;22(11):2153-62.
• [7] 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.
• [8] 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.
• [9] Gene Expression Regulation and Pathway Analysis After Valproic Acid and Carbamazepine Exposure in a Human Embryonic Stem Cell-Based Neurodevelopmental Toxicity Assay. Toxicol Sci. 2015 Aug;146(2):311-20. doi: 10.1093/toxsci/kfv094. Epub 2015 May 15.
• [10] Expression profile analysis of colon cancer cells in response to sulindac or aspirin. Biochem Biophys Res Commun. 2002 Mar 29;292(2):498-512.
• [11] Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss. J Clin Endocrinol Metab. 2007 Jul;92(7):2793-802. doi: 10.1210/jc.2006-2722. Epub 2007 Apr 17.
• [12] Novel ATP-competitive Akt inhibitor afuresertib suppresses the proliferation of malignant pleural mesothelioma cells. Cancer Med. 2017 Nov;6(11):2646-2659. doi: 10.1002/cam4.1179. Epub 2017 Sep 27.
• [13] New insights into BaP-induced toxicity: role of major metabolites in transcriptomics and contribution to hepatocarcinogenesis. Arch Toxicol. 2016 Jun;90(6):1449-58.
• [14] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [15] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.