Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTCS7EM6)

• DOT Name: Leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3)
• Gene Name: LRRTM3
• Related Disease:
  Alzheimer disease
  Amyloidosis
  Autism spectrum disorder
  Essential tremor
• UniProt ID: LRRT3_HUMAN
• Pfam ID: PF00560 ; PF13855
• Sequence:
  MGFNVIRLLSGSAVALVIAPTVLLTMLSSAERGCPKGCRCEGKMVYCESQKLQEIPSSIS
  AGCLGLSLRYNSLQKLKYNQFKGLNQLTWLYLDHNHISNIDENAFNGIRRLKELILSSNR
  ISYFLNNTFRPVTNLRNLDLSYNQLHSLGSEQFRGLRKLLSLHLRSNSLRTIPVRIFQDC
  RNLELLDLGYNRIRSLARNVFAGMIRLKELHLEHNQFSKLNLALFPRLVSLQNLYLQWNK
  ISVIGQTMSWTWSSLQRLDLSGNEIEAFSGPSVFQCVPNLQRLNLDSNKLTFIGQEILDS
  WISLNDISLAGNIWECSRNICSLVNWLKSFKGLRENTIICASPKELQGVNVIDAVKNYSI
  CGKSTTERFDLARALPKPTFKPKLPRPKHESKPPLPPTVGATEPGPETDADAEHISFHKI
  IAGSVALFLSVLVILLVIYVSWKRYPASMKQLQQRSLMRRHRKKKRQSLKQMTPSTQEFY
  VDYKPTNTETSEMLLNGTGPCTYNKSGSRECEIPLSMNVSTFLAYDQPTISYCGVHHELL
  SHKSFETNAQEDTMETHLETELDLSTITTAGRISDHKQQLA
• Function: Exhibits a limited synaptogenic activity in vitro, restricted to excitatory presynaptic differentiation. May play a role in the development and maintenance of the vertebrate nervous system.
• Tissue Specificity: Expressed in neuronal tissues.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Alzheimer disease	DISF8S70	Strong	Biomarker	[1]
Amyloidosis	DISHTAI2	Strong	Biomarker	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Essential tremor	DIS7GBKQ	Strong	Genetic Variation	[4]

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

Drug Name	Drug ID	Highest Status	Interaction	REF
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3).	[5]
Phenobarbital	DMXZOCG	Approved	Phenobarbital decreases the expression of Leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3).	[6]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 increases the expression of Leucine-rich repeat transmembrane neuronal protein 3 (LRRTM3).	[7]

References

• [1] Association of LRRTM3 polymorphisms with late-onset Alzheimer's disease in Han Chinese.Exp Gerontol. 2014 Apr;52:18-22. doi: 10.1016/j.exger.2014.01.013. Epub 2014 Jan 21.
• [2] The pre-eclampsia gene STOX1 controls a conserved pathway in placenta and brain upregulated in late-onset Alzheimer's disease.J Alzheimers Dis. 2010;19(2):673-9. doi: 10.3233/JAD-2010-1265.
• [3] Polymorphisms in leucine-rich repeat genes are associated with autism spectrum disorder susceptibility in populations of European ancestry.Mol Autism. 2010 Mar 25;1(1):7. doi: 10.1186/2040-2392-1-7.
• [4] Genome-wide association study in essential tremor identifies three new loci.Brain. 2016 Dec;139(Pt 12):3163-3169. doi: 10.1093/brain/aww242. Epub 2016 Oct 20.
• [5] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [6] Dose- and time-dependent effects of phenobarbital on gene expression profiling in human hepatoma HepaRG cells. Toxicol Appl Pharmacol. 2009 Feb 1;234(3):345-60.
• [7] 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.