Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT7X0AA7)

• DOT Name: Leucine-rich repeat neuronal protein 3 (LRRN3)
• Synonyms: Neuronal leucine-rich repeat protein 3; NLRR-3
• Gene Name: LRRN3
• Related Disease:
  Neuroblastoma
  Autism
  Autism spectrum disorder
  Schizophrenia
• UniProt ID: LRRN3_HUMAN
• Pfam ID: PF00041 ; PF07679 ; PF13855
• Sequence:
  MKDMPLRIHVLLGLAITTLVQAVDKKVDCPRLCTCEIRPWFTPRSIYMEASTVDCNDLGL
  LTFPARLPANTQILLLQTNNIAKIEYSTDFPVNLTGLDLSQNNLSSVTNINVKKMPQLLS
  VYLEENKLTELPEKCLSELSNLQELYINHNLLSTISPGAFIGLHNLLRLHLNSNRLQMIN
  SKWFDALPNLEILMIGENPIIRIKDMNFKPLINLRSLVIAGINLTEIPDNALVGLENLES
  ISFYDNRLIKVPHVALQKVVNLKFLDLNKNPINRIRRGDFSNMLHLKELGINNMPELISI
  DSLAVDNLPDLRKIEATNNPRLSYIHPNAFFRLPKLESLMLNSNALSALYHGTIESLPNL
  KEISIHSNPIRCDCVIRWMNMNKTNIRFMEPDSLFCVDPPEFQGQNVRQVHFRDMMEICL
  PLIAPESFPSNLNVEAGSYVSFHCRATAEPQPEIYWITPSGQKLLPNTLTDKFYVHSEGT
  LDINGVTPKEGGLYTCIATNLVGADLKSVMIKVDGSFPQDNNGSLNIKIRDIQANSVLVS
  WKASSKILKSSVKWTAFVKTENSHAAQSARIPSDVKVYNLTHLNPSTEYKICIDIPTIYQ
  KNRKKCVNVTTKGLHPDQKEYEKNNTTTLMACLGGLLGIIGVICLISCLSPEMNCDGGHS
  YVRNYLQKPTFALGELYPPLINLWEAGKEKSTSLKVKATVIGLPTNMS

Molecular Interaction Atlas (MIA) of This DOT

4 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Neuroblastoma	DISVZBI4	Definitive	Biomarker	[1]
Autism	DISV4V1Z	Strong	Genetic Variation	[2]
Autism spectrum disorder	DISXK8NV	Strong	Biomarker	[3]
Schizophrenia	DISSRV2N	Strong	Genetic Variation	[4]

15 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 neuronal protein 3 (LRRN3).	[5]
Tretinoin	DM49DUI	Approved	Tretinoin decreases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[6]
Doxorubicin	DMVP5YE	Approved	Doxorubicin decreases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[7]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[8]
Vorinostat	DMWMPD4	Approved	Vorinostat increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[9]
Methotrexate	DM2TEOL	Approved	Methotrexate increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[10]
Panobinostat	DM58WKG	Approved	Panobinostat increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[9]
Cytarabine	DMZD5QR	Approved	Cytarabine increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[11]
SNDX-275	DMH7W9X	Phase 3	SNDX-275 increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[9]
Curcumin	DMQPH29	Phase 3	Curcumin increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[12]
Belinostat	DM6OC53	Phase 2	Belinostat increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[9]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[13]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[14]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A decreases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[15]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Leucine-rich repeat neuronal protein 3 (LRRN3).	[16]

References

• [1] Intracellular fragment of NLRR3 (NLRR3-ICD) stimulates ATRA-dependent neuroblastoma differentiation.Biochem Biophys Res Commun. 2014 Oct 10;453(1):86-93. doi: 10.1016/j.bbrc.2014.09.065. Epub 2014 Sep 23.
• [2] Examination of NRCAM, LRRN3, KIAA0716, and LAMB1 as autism candidate genes.BMC Med Genet. 2004 May 5;5:12. doi: 10.1186/1471-2350-5-12.
• [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 Detected Novel Susceptibility Genes for Schizophrenia and Shared Trans-Populations/Diseases Genetic Effect.Schizophr Bull. 2019 Jun 18;45(4):824-834. doi: 10.1093/schbul/sby140.
• [5] Human embryonic stem cell-derived test systems for developmental neurotoxicity: a transcriptomics approach. Arch Toxicol. 2013 Jan;87(1):123-43.
• [6] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [7] Bringing in vitro analysis closer to in vivo: studying doxorubicin toxicity and associated mechanisms in 3D human microtissues with PBPK-based dose modelling. Toxicol Lett. 2018 Sep 15;294:184-192.
• [8] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [9] 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.
• [10] Global molecular effects of tocilizumab therapy in rheumatoid arthritis synovium. Arthritis Rheumatol. 2014 Jan;66(1):15-23.
• [11] Cytosine arabinoside induces ectoderm and inhibits mesoderm expression in human embryonic stem cells during multilineage differentiation. Br J Pharmacol. 2011 Apr;162(8):1743-56.
• [12] Gene-expression profiling during curcumin-induced apoptosis reveals downregulation of CXCR4. Exp Hematol. 2007 Jan;35(1):84-95.
• [13] Genome-wide transcriptional and functional analysis of human T lymphocytes treated with benzo[alpha]pyrene. Int J Mol Sci. 2018 Nov 17;19(11).
• [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] Bisphenol A induces DSB-ATM-p53 signaling leading to cell cycle arrest, senescence, autophagy, stress response, and estrogen release in human fetal lung fibroblasts. Arch Toxicol. 2018 Apr;92(4):1453-1469.
• [16] 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.