Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1LN60D)

• DOT Name: Trafficking protein particle complex subunit 2-like protein (TRAPPC2L)
• Gene Name: TRAPPC2L
• Related Disease:
  Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis
  Melanoma
  Mucopolysaccharidosis type 4A
  Parkinson disease
• UniProt ID: TPC2L_HUMAN
• Pfam ID: PF04628
• Sequence:
  MAVCIAVIAKENYPLYIRSTPTENELKFHYMVHTSLDVVDEKISAMGKALVDQRELYLGL
  LYPTEDYKVYGYVTNSKVKFVMVVDSSNTALRDNEIRSMFRKLHNSYTDVMCNPFYNPGD
  RIQSSRAFDNMVTSMMIQVC
• Function: Plays a role in vesicular transport from endoplasmic reticulum to Golgi.
• Tissue Specificity: Expressed in testis, liver, bladder, lung, spleen and brain, several cell lines and primary chondrocytes cell line.
• 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

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis	DIST7CLF	Strong	Autosomal recessive	[1]
Melanoma	DIS1RRCY	Strong	Biomarker	[2]
Mucopolysaccharidosis type 4A	DISTYFQS	Strong	Genetic Variation	[3]
Parkinson disease	DISQVHKL	Strong	Genetic Variation	[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 2-like protein (TRAPPC2L).	[4]

5 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 2-like protein (TRAPPC2L).	[5]
Doxorubicin	DMVP5YE	Approved	Doxorubicin affects the expression of Trafficking protein particle complex subunit 2-like protein (TRAPPC2L).	[6]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Trafficking protein particle complex subunit 2-like protein (TRAPPC2L).	[7]
Triclosan	DMZUR4N	Approved	Triclosan increases the expression of Trafficking protein particle complex subunit 2-like protein (TRAPPC2L).	[8]
Milchsaure	DM462BT	Investigative	Milchsaure decreases the expression of Trafficking protein particle complex subunit 2-like protein (TRAPPC2L).	[9]

References

• [1] Bi-allelic mutations in TRAPPC2L result in a neurodevelopmental disorder and have an impact on RAB11 in fibroblasts. J Med Genet. 2018 Nov;55(11):753-764. doi: 10.1136/jmedgenet-2018-105441. Epub 2018 Aug 17.
• [2] Overlapping genetic architecture between Parkinson disease and melanoma.Acta Neuropathol. 2020 Feb;139(2):347-364. doi: 10.1007/s00401-019-02110-z. Epub 2019 Dec 16.
• [3] Molecular testing of 163 patients with Morquio A (Mucopolysaccharidosis IVA) identifies 39 novel GALNS mutations.Mol Genet Metab. 2014 Jun;112(2):160-70. doi: 10.1016/j.ymgme.2014.03.004. Epub 2014 Mar 20.
• [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] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [7] 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.
• [8] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [9] Transcriptional profiling of lactic acid treated reconstructed human epidermis reveals pathways underlying stinging and itch. Toxicol In Vitro. 2019 Jun;57:164-173.