Details of Drug Off-Target (DOT)

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

DOT Name Laminin subunit gamma-3 (LAMC3)
Synonyms Laminin-12 subunit gamma; Laminin-14 subunit gamma; Laminin-15 subunit gamma
Gene Name LAMC3
Related Disease
Occipital pachygyria and polymicrogyria ( )
Advanced cancer ( )
Alzheimer disease ( )
Brain disease ( )
Epilepsy ( )
Oral cancer ( )
Pharynx neoplasm ( )
Endometriosis ( )
Type-1/2 diabetes ( )
Autism spectrum disorder ( )
Complex neurodevelopmental disorder ( )
UniProt ID
LAMC3_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF00052 ; PF00053 ; PF00055
Sequence
MAAAALLLGLALLAPRAAGAGMGACYDGAGRPQRCLPVFENAAFGRLAQASHTCGSPPED
FCPHVGAAGAGAHCQRCDAADPQRHHNASYLTDFHSQDESTWWQSPSMAFGVQYPTSVNI
TLRLGKAYEITYVRLKFHTSRPESFAIYKRSRADGPWEPYQFYSASCQKTYGRPEGQYLR
PGEDERVAFCTSEFSDISPLSGGNVAFSTLEGRPSAYNFEESPGLQEWVTSTELLISLDR
LNTFGDDIFKDPKVLQSYYYAVSDFSVGGRCKCNGHASECGPDVAGQLACRCQHNTTGTD
CERCLPFFQDRPWARGTAEAAHECLPCNCSGRSEECTFDRELFRSTGHGGRCHHCRDHTA
GPHCERCQENFYHWDPRMPCQPCDCQSAGSLHLQCDDTGTCACKPTVTGWKCDRCLPGFH
SLSEGGCRPCTCNPAGSLDTCDPRSGRCPCKENVEGNLCDRCRPGTFNLQPHNPAGCSSC
FCYGHSKVCASTAQFQVHHILSDFHQGAEGWWARSVGGSEHPPQWSPNGVLLSPEDEEEL
TAPEKFLGDQRFSYGQPLILTFRVPPGDSPLPVQLRLEGTGLALSLRHSSLSGPQDAGHP
REVELRFHLQETSEDVAPPLPPFHFQRLLANLTSLRLRVSPGPSPAGPVFLTEVRLTSAR
PGLSPPASWVEICSCPTGYTGQFCESCAPGYKREMPQGGPYASCVPCTCNQHGTCDPNTG
ICVCSHHTEGPSCERCLPGFYGNPFAGQADDCQPCPCPGQSACTTIPESREVVCTHCPPG
QRGRRCEVCDDGFFGDPLGLFGHPQPCHQCQCSGNVDPNAVGNCDPLSGHCLRCLHNTTG
DHCEHCQEGFYGSALAPRPADKCMPCSCHPQGSVSEQMPCDPVTGQCSCLPHVTARDCSR
CYPGFFDLQPGRGCRSCKCHPLGSQEDQCHPKTGQCTCRPGVTGQACDRCQLGFFGFSIK
GCRACRCSPLGAASAQCHENGTCVCRPGFEGYKCDRCHDNFFLTADGTHCQQCPSCYALV
KEEAAKLKARLTLTEGWLQGSDCGSPWGPLDILLGEAPRGDVYQGHHLLPGAREAFLEQM
MSLEGAVKAAREQLQRLNKGARCAQAGSQKTCTQLADLEAVLESSEEEILHAAAILASLE
IPQEGPSQPTKWSHLATEARALARSHRDTATKIAATAWRALLASNTSYALLWNLLEGRVA
LETQRDLEDRYQEVQAAQKALRTAVAEVLPEAESVLATVQQVGADTAPYLALLASPGALP
QKSRAEDLGLKAKALEKTVASWQHMATEAARTLQTAAQATLRQTEPLTKLHQEARAALTQ
ASSSVQAATVTVMGARTLLADLEGMKLQFPRPKDQAALQRKADSVSDRLLADTRKKTKQA
ERMLGNAAPLSSSAKKKGREAEVLAKDSAKLAKALLRERKQAHRRASRLTSQTQATLQQA
SQQVLASEARRQELEEAERVGAGLSEMEQQIRESRISLEKDIETLSELLARLGSLDTHQA
PAQALNETQWALERLRLQLGSPGSLQRKLSLLEQESQQQELQIQGFESDLAEIRADKQNL
EAILHSLPENCASWQ
Function
Binding to cells via a high affinity receptor, laminin is thought to mediate the attachment, migration and organization of cells into tissues during embryonic development by interacting with other extracellular matrix components.
Tissue Specificity Broadly expressed in: skin, heart, lung, and the reproductive tracts.
KEGG Pathway
PI3K-Akt sig.ling pathway (hsa04151 )
Focal adhesion (hsa04510 )
ECM-receptor interaction (hsa04512 )
Toxoplasmosis (hsa05145 )
Amoebiasis (hsa05146 )
Human papillomavirus infection (hsa05165 )
Pathways in cancer (hsa05200 )
Small cell lung cancer (hsa05222 )
Reactome Pathway
Non-integrin membrane-ECM interactions (R-HSA-3000171 )
MET activates PTK2 signaling (R-HSA-8874081 )
Laminin interactions (R-HSA-3000157 )

Molecular Interaction Atlas (MIA) of This DOT

11 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Occipital pachygyria and polymicrogyria DISIAYWB Definitive Autosomal recessive [1]
Advanced cancer DISAT1Z9 Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Genetic Variation [3]
Brain disease DIS6ZC3X Strong Biomarker [1]
Epilepsy DISBB28L Strong Genetic Variation [4]
Oral cancer DISLD42D Strong Genetic Variation [5]
Pharynx neoplasm DISQCA3F Strong Genetic Variation [5]
Endometriosis DISX1AG8 moderate Genetic Variation [6]
Type-1/2 diabetes DISIUHAP moderate Biomarker [7]
Autism spectrum disorder DISXK8NV Disputed Biomarker [8]
Complex neurodevelopmental disorder DISB9AFI Disputed Autosomal dominant [9]
------------------------------------------------------------------------------------
⏷ Show the Full List of 11 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate increases the methylation of Laminin subunit gamma-3 (LAMC3). [10]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene increases the methylation of Laminin subunit gamma-3 (LAMC3). [15]
------------------------------------------------------------------------------------
8 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Tretinoin DM49DUI Approved Tretinoin increases the expression of Laminin subunit gamma-3 (LAMC3). [11]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Laminin subunit gamma-3 (LAMC3). [12]
Cisplatin DMRHGI9 Approved Cisplatin increases the expression of Laminin subunit gamma-3 (LAMC3). [13]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Laminin subunit gamma-3 (LAMC3). [11]
Alitretinoin DMME8LH Approved Alitretinoin increases the expression of Laminin subunit gamma-3 (LAMC3). [11]
SNDX-275 DMH7W9X Phase 3 SNDX-275 increases the expression of Laminin subunit gamma-3 (LAMC3). [14]
Bisphenol A DM2ZLD7 Investigative Bisphenol A decreases the expression of Laminin subunit gamma-3 (LAMC3). [16]
all-trans-4-oxo-retinoic acid DMM2R1N Investigative all-trans-4-oxo-retinoic acid increases the expression of Laminin subunit gamma-3 (LAMC3). [11]
------------------------------------------------------------------------------------
⏷ Show the Full List of 8 Drug(s)

References

1 Recessive LAMC3 mutations cause malformations of occipital cortical development. Nat Genet. 2011 Jun;43(6):590-4. doi: 10.1038/ng.836. Epub 2011 May 15.
2 A novel messenger RNA and long noncoding RNA signature associated with the progression of nonmuscle invasive bladder cancer.J Cell Biochem. 2019 May;120(5):8101-8109. doi: 10.1002/jcb.28089. Epub 2018 Nov 13.
3 Family-based genome scan for age at onset of late-onset Alzheimer's disease in whole exome sequencing data.Genes Brain Behav. 2015 Nov;14(8):607-17. doi: 10.1111/gbb.12250. Epub 2015 Sep 23.
4 A novel mutation in LAMC3 associated with generalized polymicrogyria of the cortex and epilepsy.Neurogenetics. 2018 Jan;19(1):61-65. doi: 10.1007/s10048-017-0534-4. Epub 2017 Dec 15.
5 Genome-wide association analyses identify new susceptibility loci for oral cavity and pharyngeal cancer.Nat Genet. 2016 Dec;48(12):1544-1550. doi: 10.1038/ng.3685. Epub 2016 Oct 17.
6 Genome-wide genetic analyses highlight mitogen-activated protein kinase (MAPK) signaling in the pathogenesis of endometriosis.Hum Reprod. 2017 Apr 1;32(4):780-793. doi: 10.1093/humrep/dex024.
7 Enhanced wound healing, kinase and stem cell marker expression in diabetic organ-cultured human corneas upon MMP-10 and cathepsin F gene silencing.Invest Ophthalmol Vis Sci. 2013 Dec 17;54(13):8172-80. doi: 10.1167/iovs.13-13233.
8 Targeted sequencing identifies 91 neurodevelopmental-disorder risk genes with autism and developmental-disability biases. Nat Genet. 2017 Apr;49(4):515-526. doi: 10.1038/ng.3792. Epub 2017 Feb 13.
9 Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
10 Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
11 Retinoic acid and its 4-oxo metabolites are functionally active in human skin cells in vitro. J Invest Dermatol. 2005 Jul;125(1):143-53.
12 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.
13 Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
14 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.
15 Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
16 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.