Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTWL5H45)

• DOT Name: Trafficking protein particle complex subunit 2 (TRAPPC2)
• Synonyms: Sedlin
• Gene Name: TRAPPC2
• Related Disease:
  Spondyloepiphyseal dysplasia tarda, X-linked
  Intellectual disability
  Isolated congenital microcephaly
  Morquio syndrome
  Osteochondrodysplasia
  Spondyloepiphyseal dysplasia tarda
  Spondyloepiphyseal dysplasia
• UniProt ID: TPC2A_HUMAN
• Pfam ID: PF04628
• Sequence:
  MSGSFYFVIVGHHDNPVFEMEFLPAGKAESKDDHRHLNQFIAHAALDLVDENMWLSNNMY
  LKTVDKFNEWFVSAFVTAGHMRFIMLHDIRQEDGIKNFFTDVYDLYIKFSMNPFYEPNSP
  IRSSAFDRKVQFLGKKHLLS
• Function: Prevents transcriptional repression and induction of cell death by ENO1. May play a role in vesicular transport from endoplasmic reticulum to Golgi.
• Tissue Specificity: Expressed in brain, heart, kidney, liver, lung, pancreas, placenta, skeletal muscle, fetal cartilage, fibroblasts, placenta and lymphocytes.
• 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

7 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Spondyloepiphyseal dysplasia tarda, X-linked	DIS9EL3M	Definitive	X-linked recessive	[1]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[2]
Isolated congenital microcephaly	DISUXHZ6	Strong	Genetic Variation	[2]
Morquio syndrome	DIS2Y2P2	Strong	Genetic Variation	[3]
Osteochondrodysplasia	DIS9SPWW	Strong	Genetic Variation	[4]
Spondyloepiphyseal dysplasia tarda	DISKGY38	Supportive	Autosomal dominant	[5]
Spondyloepiphyseal dysplasia	DIS1JG9A	Limited	Genetic Variation	[6]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Trafficking protein particle complex subunit 2 (TRAPPC2).	[7]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene affects the methylation of Trafficking protein particle complex subunit 2 (TRAPPC2).	[11]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Trafficking protein particle complex subunit 2 (TRAPPC2).	[8]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Trafficking protein particle complex subunit 2 (TRAPPC2).	[9]
Diethylstilbestrol	DMN3UXQ	Approved	Diethylstilbestrol increases the expression of Trafficking protein particle complex subunit 2 (TRAPPC2).	[10]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Trafficking protein particle complex subunit 2 (TRAPPC2).	[12]

References

• [1] Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
• [2] The adaptor function of TRAPPC2 in mammalian TRAPPs explains TRAPPC2-associated SEDT and TRAPPC9-associated congenital intellectual disability.PLoS One. 2011;6(8):e23350. doi: 10.1371/journal.pone.0023350. Epub 2011 Aug 15.
• [3] Mutational analysis in X-linked spondyloepiphyseal dysplasia tarda.J Clin Endocrinol Metab. 2001 Jul;86(7):3233-6. doi: 10.1210/jcem.86.7.7688.
• [4] [Identification of a missense mutation in SEDL gene from a Chinese family with X-linked spondyloepiphyseal dysplasia tarda].Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2008 Feb;25(1):15-8.
• [5] X-Linked Spondyloepiphyseal Dysplasia Tarda. 2001 Nov 1 [updated 2023 Apr 6]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [6] A novel nonsense mutation in the sedlin gene (SEDL) causes severe spondyloepiphyseal dysplasia tarda in a five-generation Chinese pedigree.Genet Mol Res. 2014 Apr 29;13(2):3362-70. doi: 10.4238/2014.April.29.15.
• [7] 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.
• [8] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [9] 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.
• [10] Identification of biomarkers and outcomes of endocrine disruption in human ovarian cortex using In Vitro Models. Toxicology. 2023 Feb;485:153425. doi: 10.1016/j.tox.2023.153425. Epub 2023 Jan 5.
• [11] 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.
• [12] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.