Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT1UFECZ)

• DOT Name: Tectonin beta-propeller repeat-containing protein 2 (TECPR2)
• Synonyms: WD repeat-containing protein KIAA0329/KIAA0297
• Gene Name: TECPR2
• Related Disease:
  Autonomic neuropathy
  Riley-Day syndrome
  Alzheimer disease
  Hereditary spastic paraplegia 49
  Intellectual disability
  Motor neurone disease
  Neuroaxonal dystrophy
  Neurodegeneration with brain iron accumulation 2A
  Pantothenate kinase-associated neurodegeneration
  Vascular purpura
  Hereditary spastic paraplegia
• UniProt ID: TCPR2_HUMAN
• Pfam ID: PF06462 ; PF19193
• Sequence:
  MASISEPVTFREFCPLYYLLNAIPTKIQKGFRSIVVYLTALDTNGDYIAVGSSIGMLYLY
  CRHLNQMRKYNFEGKTESITVVKLLSCFDDLVAAGTASGRVAVFQLVSSLPGRNKQLRRF
  DVTGIHKNSITALAWSPNGMKLFSGDDKGKIVYSSLDLDQGLCNSQLVLEEPSSIVQLDY
  SQKVLLVSTLQRSLLFYTEEKSVRQIGTQPRKSTGKFGACFIPGLCKQSDLTLYASRPGL
  RLWKADVHGTVQATFILKDAFAGGVKPFELHPRLESPNSGSCSLPERHLGLVSCFFQEGW
  VLSWNEYSIYLLDTVNQATVAGLEGSGDIVSVSCTENEIFFLKGDRNIIRISSRPEGLTS
  TVRDGLEMSGCSERVHVQQAEKLPGATVSETRLRGSSMASSVASEPRSRSSSLNSTDSGS
  GLLPPGLQATPELGKGSQPLSQRFNAISSEDFDQELVVKPIKVKRKKKKKKTEGGSRSTC
  HSSLESTPCSEFPGDSPQSLNTDLLSMTSSVLGSSVDQLSAESPDQESSFNGEVNGVPQE
  NTDPETFNVLEVSGSMPDSLAEEDDIRTEMPHCHHAHGRELLNGAREDVGGSDVTGLGDE
  PCPADDGPNSTQLPFQEQDSSPGAHDGEDIQPIGPQSTFCEVPLLNSLTVPSSLSWAPSA
  EQWLPGTRADEGSPVEPSQEQDILTSMEASGHLSTNLWHAVTDDDTGQKEIPISERVLGS
  VGGQLTPVSALAASTHKPWLEQPPRDQTLTSSDEEDIYAHGLPSSSSETSVTELGPSCSQ
  QDLSRLGAEDAGLLKPDQFAESWMGYSGPGYGILSLVVSEKYIWCLDYKGGLFCSALPGA
  GLRWQKFEDAVQQVAVSPSGALLWKIEQKSNRAFACGKVTIKGKRHWYEALPQAVFVALS
  DDTAWIIRTSGDLYLQTGLSVDRPCARAVKVDCPYPLSQITARNNVVWALTEQRALLYRE
  GVSSFCPEGEQWKCDIVSERQALEPVCITLGDQQTLWALDIHGNLWFRTGIISKKPQGDD
  DHWWQVSITDYVVFDQCSLFQTIIHATHSVATAAQAPVEKVADKLRMAFWSQQLQCQPSL
  LGVNNSGVWISSGKNEFHVAKGSLIGTYWNHVVPRGTASATKWAFVLASAAPTKEGSFLW
  LCQSSKDLCSVSAQSAQSRPSTVQLPPEAEMRAYAACQDALWALDSLGQVFIRTLSKSCP
  TGMHWTRLDLSQLGAVKLTSLACGNQHIWACDSRGGVYFRVGTQPLNPSLMLPAWIMIEP
  PVQPAGVSLVSVHSSPNDQMLWVLDSRWNVHVRTGITEEMPVGTAWEHVPGLQACQLALS
  TRTVWARCPNGDLARRYGVTDKNPAGDYWKKIPGSVSCFTVTASDELWAVGPPGYLLQRL
  TKTFSHSHGTQKSSQAAMPHPEDLEDEWEVI
• Function: Probably plays a role as positive regulator of autophagy.
• Tissue Specificity: Detected in skin fibroblast (at protein level).

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Autonomic neuropathy	DISI3WJ0	Definitive	Genetic Variation	[1]
Riley-Day syndrome	DISJZHNP	Definitive	Genetic Variation	[1]
Alzheimer disease	DISF8S70	Strong	Biomarker	[2]
Hereditary spastic paraplegia 49	DISC886M	Strong	Autosomal recessive	[3]
Intellectual disability	DISMBNXP	Strong	Genetic Variation	[1]
Motor neurone disease	DISUHWUI	Strong	Biomarker	[4]
Neuroaxonal dystrophy	DISHSV8Z	Strong	Biomarker	[5]
Neurodegeneration with brain iron accumulation 2A	DIS9XEBF	Strong	Biomarker	[5]
Pantothenate kinase-associated neurodegeneration	DIS50V55	Strong	Genetic Variation	[5]
Vascular purpura	DIS6ZZMF	Strong	Biomarker	[6]
Hereditary spastic paraplegia	DISGZQV1	Limited	Biomarker	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate affects the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[7]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[9]
Menadione	DMSJDTY	Approved	Menadione affects the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[11]
Azacitidine	DMTA5OE	Approved	Azacitidine increases the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[12]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene decreases the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 increases the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[14]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[15]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the methylation of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[8]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Tectonin beta-propeller repeat-containing protein 2 (TECPR2).	[10]

References

• [1] TECPR2 mutations cause a new subtype of familial dysautonomia like hereditary sensory autonomic neuropathy with intellectual disability.Eur J Paediatr Neurol. 2016 Jan;20(1):69-79. doi: 10.1016/j.ejpn.2015.10.003. Epub 2015 Oct 22.
• [2] Neuropathology-driven Whole-genome Sequencing Study Points to Novel Candidate Genes for Healthy Brain Aging.Alzheimer Dis Assoc Disord. 2019 Jan-Mar;33(1):7-14. doi: 10.1097/WAD.0000000000000294.
• [3] Mutation in TECPR2 reveals a role for autophagy in hereditary spastic paraparesis. Am J Hum Genet. 2012 Dec 7;91(6):1065-72. doi: 10.1016/j.ajhg.2012.09.015. Epub 2012 Nov 21.
• [4] WES in a family trio suggests involvement of TECPR2 in a complex form of progressive motor neuron disease.Clin Genet. 2016 Aug;90(2):182-5. doi: 10.1111/cge.12730. Epub 2016 Feb 10.
• [5] TECPR2 Associated Neuroaxonal Dystrophy in Spanish Water Dogs.PLoS One. 2015 Nov 10;10(11):e0141824. doi: 10.1371/journal.pone.0141824. eCollection 2015.
• [6] TECPR2 Cooperates with LC3C to Regulate COPII-Dependent ER Export.Mol Cell. 2015 Oct 1;60(1):89-104. doi: 10.1016/j.molcel.2015.09.010.
• [7] 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.
• [8] Integrative "-Omics" analysis in primary human hepatocytes unravels persistent mechanisms of cyclosporine A-induced cholestasis. Chem Res Toxicol. 2016 Dec 19;29(12):2164-2174.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [11] Global gene expression analysis reveals differences in cellular responses to hydroxyl- and superoxide anion radical-induced oxidative stress in caco-2 cells. Toxicol Sci. 2010 Apr;114(2):193-203. doi: 10.1093/toxsci/kfp309. Epub 2009 Dec 31.
• [12] The DNA methyltransferase inhibitors azacitidine, decitabine and zebularine exert differential effects on cancer gene expression in acute myeloid leukemia cells. Leukemia. 2009 Jun;23(6):1019-28.
• [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] Inhibition of BRD4 attenuates tumor cell self-renewal and suppresses stem cell signaling in MYC driven medulloblastoma. Oncotarget. 2014 May 15;5(9):2355-71.
• [15] Cell-based two-dimensional morphological assessment system to predict cancer drug-induced cardiotoxicity using human induced pluripotent stem cell-derived cardiomyocytes. Toxicol Appl Pharmacol. 2019 Nov 15;383:114761. doi: 10.1016/j.taap.2019.114761. Epub 2019 Sep 15.