Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTF6EAQX)

• DOT Name: Trafficking protein particle complex subunit 10 (TRAPPC10)
• Synonyms: Epilepsy holoprosencephaly candidate 1 protein; EHOC-1; Protein GT334; Trafficking protein particle complex subunit TMEM1; Transport protein particle subunit TMEM1; TRAPP subunit TMEM1
• Gene Name: TRAPPC10
• Related Disease:
  Epilepsy
  Neurodevelopmental disorder with microcephaly, short stature, and speech delay
  Skin disease
  Unverricht-Lundborg syndrome
  Laryngeal squamous cell carcinoma
• UniProt ID: TPC10_HUMAN
• Pfam ID: PF12584
• Sequence:
  MDASEEPLPPVIYTMENKPIVTCAGDQNLFTSVYPTLSQQLPREPMEWRRSYGRAPKMIH
  LESNFVQFKEELLPKEGNKALLTFPFLHIYWTECCDTEVYKATVKDDLTKWQNVLKAHSS
  VDWLIVIVENDAKKKNKTNILPRTSIVDKIRNDFCNKQSDRCVVLSDPLKDSSRTQESWN
  AFLTKLRTLLLMSFTKNLGKFEDDMRTLREKRTEPGWSFCEYFMVQEELAFVFEMLQQFE
  DALVQYDELDALFSQYVVNFGAGDGANWLTFFCQPVKSWNGLILRKPIDMEKRESIQRRE
  ATLLDLRSYLFSRQCTLLLFLQRPWEVAQRALELLHNCVQELKLLEVSVPPGALDCWVFL
  SCLEVLQRIEGCCDRAQIDSNIAHTVGLWSYATEKLKSLGYLCGLVSEKGPNSEDLNRTV
  DLLAGLGAERPETANTAQSPYKKLKEALSSVEAFEKHYLDLSHATIEMYTSIGRIRSAKF
  VGKDLAEFYMRKKAPQKAEIYLQGALKNYLAEGWALPITHTRKQLAECQKHLGQIENYLQ
  TSSLLASDHHLTEEERKHFCQEILDFASQPSDSPGHKIVLPMHSFAQLRDLHFDPSNAVV
  HVGGVLCVEITMYSQMPVPVHVEQIVVNVHFSIEKNSYRKTAEWLTKHKTSNGIINFPPE
  TAPFPVSQNSLPALELYEMFERSPSDNSLNTTGIICRNVHMLLRRQESSSSLEMPSGVAL
  EEGAHVLRCSHVTLEPGANQITFRTQAKEPGTYTLRQLCASVGSVWFVLPHIYPIVQYDV
  YSQEPQLHVEPLADSLLAGIPQRVKFTVTTGHYTIKNGDSLQLSNAEAMLILCQAESRAV
  VYSNTREQSSEAALRIQSSDKVTSISLPVAPAYHVIEFELEVLSLPSAPALGGESDMLGM
  AEPHRKHKDKQRTGRCMVTTDHKVSIDCPWSIYSTVIALTFSVPFRTTHSLLSSGTRKYV
  QVCVQNLSELDFQLSDSYLVDTGDSTDLQLVPLNTQSQQPIYSKQSVFFVWELKWTEEPP
  PSLHCRFSVGFSPASEEQLSISLKPYTYEFKVENFFTLYNVKAEIFPPSGMEYCRTGSLC
  SLEVLITRLSDLLEVDKDEALTESDEHFSTKLMYEVVDNSSNWAVCGKSCGVISMPVAAR
  ATHRVHMEVMPLFAGYLPLPDVRLFKYLPHHSAHSSQLDADSWIENDSLSVDKHGDDQPD
  SSSLKSRGSVHSACSSEHKGLPMPRLQALPAGQVFNSSSGTQVLVIPSQDDHVLEVSVT
• Function: Specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether.
• Tissue Specificity: Expressed in all tissues examined.
• 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

5 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Epilepsy	DISBB28L	Strong	Biomarker	[1]
Neurodevelopmental disorder with microcephaly, short stature, and speech delay	DISUEV69	Strong	Autosomal recessive	[2]
Skin disease	DISDW8R6	Strong	Biomarker	[3]
Unverricht-Lundborg syndrome	DISG4WLX	Strong	Biomarker	[1]
Laryngeal squamous cell carcinoma	DIS9UUVF	moderate	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[5]
Acetaminophen	DMUIE76	Approved	Acetaminophen increases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[6]
Arsenic	DMTL2Y1	Approved	Arsenic decreases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[3]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[8]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[9]
Tocopherol	DMBIJZ6	Phase 2	Tocopherol decreases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[10]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[11]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[12]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde decreases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[13]
crotylaldehyde	DMTWRQI	Investigative	crotylaldehyde decreases the expression of Trafficking protein particle complex subunit 10 (TRAPPC10).	[14]

References

• [1] Isolation and characterization of a candidate gene for progressive myoclonus epilepsy on 21q22.3.Hum Mol Genet. 1995 Apr;4(4):709-16. doi: 10.1093/hmg/4.4.709.
• [2] Novel candidate genes and variants underlying autosomal recessive neurodevelopmental disorders with intellectual disability. Hum Genet. 2018 Sep;137(9):735-752. doi: 10.1007/s00439-018-1928-6. Epub 2018 Aug 22.
• [3] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [4] lncRNA TMEM51-AS1 and RUSC1-AS1 function as ceRNAs for induction of laryngeal squamous cell carcinoma and prediction of prognosis.PeerJ. 2019 Sep 10;7:e7456. doi: 10.7717/peerj.7456. eCollection 2019.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Predictive toxicology using systemic biology and liver microfluidic "on chip" approaches: application to acetaminophen injury. Toxicol Appl Pharmacol. 2012 Mar 15;259(3):270-80.
• [7] Gene expression profiles in peripheral lymphocytes by arsenic exposure and skin lesion status in a Bangladeshi population. Cancer Epidemiol Biomarkers Prev. 2006 Jul;15(7):1367-75. doi: 10.1158/1055-9965.EPI-06-0106.
• [8] 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.
• [9] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [10] Selenium and vitamin E: cell type- and intervention-specific tissue effects in prostate cancer. J Natl Cancer Inst. 2009 Mar 4;101(5):306-20.
• [11] Environmental pollutant induced cellular injury is reflected in exosomes from placental explants. Placenta. 2020 Jan 1;89:42-49. doi: 10.1016/j.placenta.2019.10.008. Epub 2019 Oct 17.
• [12] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [13] Gene expression changes in primary human nasal epithelial cells exposed to formaldehyde in vitro. Toxicol Lett. 2010 Oct 5;198(2):289-95.
• [14] Gene expression profile and cytotoxicity of human bronchial epithelial cells exposed to crotonaldehyde. Toxicol Lett. 2010 Aug 16;197(2):113-22.