Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTKI3IU9)

• DOT Name: Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1)
• Gene Name: LRRTM1
• Related Disease:
  Schizophrenia
  Neurodevelopmental disorder
  Psychotic disorder
• UniProt ID: LRRT1_HUMAN
• Pfam ID: PF13855
• Sequence:
  MDFLLLGLCLYWLLRRPSGVVLCLLGACFQMLPAAPSGCPQLCRCEGRLLYCEALNLTEA
  PHNLSGLLGLSLRYNSLSELRAGQFTGLMQLTWLYLDHNHICSVQGDAFQKLRRVKELTL
  SSNQITQLPNTTFRPMPNLRSVDLSYNKLQALAPDLFHGLRKLTTLHMRANAIQFVPVRI
  FQDCRSLKFLDIGYNQLKSLARNSFAGLFKLTELHLEHNDLVKVNFAHFPRLISLHSLCL
  RRNKVAIVVSSLDWVWNLEKMDLSGNEIEYMEPHVFETVPHLQSLQLDSNRLTYIEPRIL
  NSWKSLTSITLAGNLWDCGRNVCALASWLNNFQGRYDGNLQCASPEYAQGEDVLDAVYAF
  HLCEDGAEPTSGHLLSAVTNRSDLGPPASSATTLADGGEGQHDGTFEPATVALPGGEHAE
  NAVQIHKVVTGTMALIFSFLIVVLVLYVSWKCFPASLRQLRQCFVTQRRKQKQKQTMHQM
  AAMSAQEYYVDYKPNHIEGALVIINEYGSCTCHQQPARECEV
• Function: Exhibits strong synaptogenic activity, restricted to excitatory presynaptic differentiation, acting at both pre- and postsynaptic level.
• Tissue Specificity: Predominantly expressed in forebrain regions including thalamus and cerebral cortex.
• Reactome Pathway: Neurexins and neuroligins (R-HSA-6794361)

Molecular Interaction Atlas (MIA) of This DOT

3 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[1]
Neurodevelopmental disorder	DIS372XH	moderate	Biomarker	[2]
Psychotic disorder	DIS4UQOT	Limited	Biomarker	[3]

9 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 Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[4]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[5]
Vorinostat	DMWMPD4	Approved	Vorinostat decreases the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[6]
Triclosan	DMZUR4N	Approved	Triclosan decreases the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[7]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[8]
Panobinostat	DM58WKG	Approved	Panobinostat affects the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[9]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[10]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 affects the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[9]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine-rich repeat transmembrane neuronal protein 1 (LRRTM1).	[11]

References

• [1] The imprinted gene LRRTM1 mediates schizotypy and handedness in a nonclinical population.J Hum Genet. 2014 Jun;59(6):332-6. doi: 10.1038/jhg.2014.30. Epub 2014 May 1.
• [2] LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia.Mol Psychiatry. 2007 Dec;12(12):1129-39, 1057. doi: 10.1038/sj.mp.4002053. Epub 2007 Jul 31.
• [3] Where and what is the right shift factor or cerebral dominance gene? A critique of Francks et al. (2007).Laterality. 2009 Jan;14(1):3-10. doi: 10.1080/13576500802574984.
• [4] Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
• [5] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [6] Definition of transcriptome-based indices for quantitative characterization of chemically disturbed stem cell development: introduction of the STOP-Toxukn and STOP-Toxukk tests. Arch Toxicol. 2017 Feb;91(2):839-864.
• [7] Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
• [8] 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.
• [9] The Bromodomain Inhibitor JQ1 and the Histone Deacetylase Inhibitor Panobinostat Synergistically Reduce N-Myc Expression and Induce Anticancer Effects. Clin Cancer Res. 2016 May 15;22(10):2534-44. doi: 10.1158/1078-0432.CCR-15-1666. Epub 2016 Jan 5.
• [10] A transcriptome-based classifier to identify developmental toxicants by stem cell testing: design, validation and optimization for histone deacetylase inhibitors. Arch Toxicol. 2015 Sep;89(9):1599-618.
• [11] 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.