General Information of Drug Off-Target (DOT) (ID: OTPL9MA3)

DOT Name Disabled homolog 1 (DAB1)
Gene Name DAB1
Related Disease
Neuroblastoma ( )
Adult glioblastoma ( )
Alzheimer disease ( )
Alzheimer disease 3 ( )
Autism ( )
Autism spectrum disorder ( )
Autosomal recessive juvenile Parkinson disease 2 ( )
Cardiac arrest ( )
Cerebellar ataxia ( )
Cerebellar degeneration ( )
Colorectal carcinoma ( )
Endometrial cancer ( )
Endometrial carcinoma ( )
Glioblastoma multiforme ( )
Mental disorder ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Paroxysmal nocturnal haemoglobinuria ( )
Retinoblastoma ( )
Acute myelogenous leukaemia ( )
Advanced cancer ( )
Coronary heart disease ( )
Spinocerebellar ataxia type 37 ( )
Corpus callosum, agenesis of ( )
Type-1/2 diabetes ( )
Breast cancer ( )
Breast carcinoma ( )
Cognitive impairment ( )
Schizophrenia ( )
Status epilepticus seizure ( )
UniProt ID
DAB1_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Pfam ID
PF21792 ; PF00640
Sequence
MSTETELQVAVKTSAKKDSRKKGQDRSEATLIKRFKGEGVRYKAKLIGIDEVSAARGDKL
CQDSMMKLKGVVAGARSKGEHKQKIFLTISFGGIKIFDEKTGALQHHHAVHEISYIAKDI
TDHRAFGYVCGKEGNHRFVAIKTAQAAEPVILDLRDLFQLIYELKQREELEKKAQKDKQC
EQAVYQTILEEDVEDPVYQYIVFEAGHEPIRDPETEENIYQVPTSQKKEGVYDVPKSQPV
SNGYSFEDFEERFAAATPNRNLPTDFDEIFEATKAVTQLELFGDMSTPPDITSPPTPATP
GDAFIPSSSQTLPASADVFSSVPFGTAAVPSGYVAMGAVLPSFWGQQPLVQQQMVMGAQP
PVAQVMPGAQPIAWGQPGLFPATQQPWPTVAGQFPPAAFMPTQTVMPLPAAMFQGPLTPL
ATVPGTSDSTRSSPQTDKPRQKMGKETFKDFQMAQPPPVPSRKPDQPSLTCTSEAFSSYF
NKVGVAQDTDDCDDFDISQLNLTPVTSTTPSTNSPPTPAPRQSSPSKSSASHASDPTTDD
IFEEGFESPSKSEEQEAPDGSQASSNSDPFGEPSGEPSGDNISPQAGS
Function Adapter molecule functioning in neural development. May regulate SIAH1 activity.
Tissue Specificity Mainly expressed in brain.
KEGG Pathway
Spinocerebellar ataxia (hsa05017 )
Reactome Pathway
Reelin signalling pathway (R-HSA-8866376 )

Molecular Interaction Atlas (MIA) of This DOT

30 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Neuroblastoma DISVZBI4 Definitive Biomarker [1]
Adult glioblastoma DISVP4LU Strong Biomarker [2]
Alzheimer disease DISF8S70 Strong Posttranslational Modification [3]
Alzheimer disease 3 DISVT69G Strong Altered Expression [4]
Autism DISV4V1Z Strong Biomarker [5]
Autism spectrum disorder DISXK8NV Strong Biomarker [6]
Autosomal recessive juvenile Parkinson disease 2 DISNSTD1 Strong Altered Expression [7]
Cardiac arrest DIS9DIA4 Strong Genetic Variation [8]
Cerebellar ataxia DIS9IRAV Strong Biomarker [9]
Cerebellar degeneration DISPBCM3 Strong Genetic Variation [8]
Colorectal carcinoma DIS5PYL0 Strong Biomarker [10]
Endometrial cancer DISW0LMR Strong Altered Expression [7]
Endometrial carcinoma DISXR5CY Strong Altered Expression [7]
Glioblastoma multiforme DISK8246 Strong Biomarker [2]
Mental disorder DIS3J5R8 Strong Biomarker [11]
Neoplasm DISZKGEW Strong Biomarker [12]
Non-small-cell lung cancer DIS5Y6R9 Strong Genetic Variation [13]
Paroxysmal nocturnal haemoglobinuria DISBHMYH Strong Genetic Variation [14]
Retinoblastoma DISVPNPB Strong Posttranslational Modification [15]
Acute myelogenous leukaemia DISCSPTN moderate Genetic Variation [16]
Advanced cancer DISAT1Z9 moderate Altered Expression [2]
Coronary heart disease DIS5OIP1 moderate Genetic Variation [17]
Spinocerebellar ataxia type 37 DIS3KNNO Supportive Autosomal dominant [8]
Corpus callosum, agenesis of DISO9P40 Disputed Biomarker [18]
Type-1/2 diabetes DISIUHAP Disputed Altered Expression [19]
Breast cancer DIS7DPX1 Limited Biomarker [12]
Breast carcinoma DIS2UE88 Limited Biomarker [12]
Cognitive impairment DISH2ERD Limited Biomarker [18]
Schizophrenia DISSRV2N Limited Biomarker [11]
Status epilepticus seizure DISY3BIC Limited Biomarker [20]
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⏷ Show the Full List of 30 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
9 Drug(s) Affected the Gene/Protein Processing of This DOT
Drug Name Drug ID Highest Status Interaction REF
Valproate DMCFE9I Approved Valproate decreases the expression of Disabled homolog 1 (DAB1). [21]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Disabled homolog 1 (DAB1). [22]
Acetaminophen DMUIE76 Approved Acetaminophen decreases the expression of Disabled homolog 1 (DAB1). [23]
Estradiol DMUNTE3 Approved Estradiol affects the expression of Disabled homolog 1 (DAB1). [24]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Disabled homolog 1 (DAB1). [25]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Disabled homolog 1 (DAB1). [26]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Disabled homolog 1 (DAB1). [28]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Disabled homolog 1 (DAB1). [29]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Disabled homolog 1 (DAB1). [30]
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⏷ Show the Full List of 9 Drug(s)
2 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Fulvestrant DM0YZC6 Approved Fulvestrant increases the methylation of Disabled homolog 1 (DAB1). [27]
Bisphenol A DM2ZLD7 Investigative Bisphenol A affects the methylation of Disabled homolog 1 (DAB1). [27]
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References

1 Reelin signalling in neuroblastoma: migratory switch in metastatic stages.Int J Oncol. 2012 Aug;41(2):681-9. doi: 10.3892/ijo.2012.1488. Epub 2012 May 18.
2 RELN signaling modulates glioblastoma growth and substrate-dependent migration.Brain Pathol. 2018 Sep;28(5):695-709. doi: 10.1111/bpa.12584. Epub 2018 Jan 10.
3 The -amyloid peptide compromises Reelin signaling in Alzheimer's disease.Sci Rep. 2016 Aug 17;6:31646. doi: 10.1038/srep31646.
4 The AICD interacting protein DAB1 is up-regulated in Alzheimer frontal cortex brain samples and causes deregulation of proteins involved in gene expression changes. Curr Alzheimer Res. 2011 Aug;8(5):573-82.
5 Association and gene-gene interactions study of reelin signaling pathway related genes with autism in the Han Chinese population.Autism Res. 2016 Apr;9(4):436-42. doi: 10.1002/aur.1540. Epub 2015 Aug 19.
6 Rare RELN variants affect Reelin-DAB1 signal transduction in autism spectrum disorder.Hum Mutat. 2018 Oct;39(10):1372-1383. doi: 10.1002/humu.23584. Epub 2018 Jul 26.
7 Disabled-1 is a large common fragile site gene, inactivated in multiple cancers.Genes Chromosomes Cancer. 2008 Feb;47(2):165-74. doi: 10.1002/gcc.20519.
8 A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia. Am J Hum Genet. 2017 Jul 6;101(1):87-103. doi: 10.1016/j.ajhg.2017.06.007.
9 Developmental abnormality contributes to cortex-dependent motor impairments and higher intracortical current requirement in the reeler homozygous mutants.Brain Struct Funct. 2018 Jul;223(6):2575-2587. doi: 10.1007/s00429-018-1647-8. Epub 2018 Mar 13.
10 Promotion of colorectal cancer invasion and metastasis through activation of NOTCH-DAB1-ABL-RHOGEF protein TRIO.Cancer Discov. 2015 Feb;5(2):198-211. doi: 10.1158/2159-8290.CD-14-0595. Epub 2014 Nov 28.
11 Dorsal Forebrain-Specific Deficiency of Reelin-Dab1 Signal Causes Behavioral Abnormalities Related to Psychiatric Disorders.Cereb Cortex. 2017 Jul 1;27(7):3485-3501. doi: 10.1093/cercor/bhv334.
12 Disabled-1 is down-regulated in clinical breast cancer and regulates cell apoptosis through NF-B/Bcl-2/caspase-9.J Cell Mol Med. 2019 Feb;23(2):1622-1627. doi: 10.1111/jcmm.14047. Epub 2018 Nov 28.
13 The 18p11.22 locus is associated with never smoker non-small cell lung cancer susceptibility in Korean populations.Hum Genet. 2012 Mar;131(3):365-72. doi: 10.1007/s00439-011-1080-z. Epub 2011 Aug 25.
14 Mutations in the HECT domain of NEDD4L lead to AKT-mTOR pathway deregulation and cause periventricular nodular heterotopia. Nat Genet. 2016 Nov;48(11):1349-1358. doi: 10.1038/ng.3676. Epub 2016 Oct 3.
15 Disabled-1 alternative splicing in human fetal retina and neural tumors.PLoS One. 2011;6(12):e28579. doi: 10.1371/journal.pone.0028579. Epub 2011 Dec 6.
16 Genome-wide haplotype association study identify the FGFR2 gene as a risk gene for acute myeloid leukemia.Oncotarget. 2017 Jan 31;8(5):7891-7899. doi: 10.18632/oncotarget.13631.
17 Genome-Wide Association and Functional Studies Identify SCML4 and THSD7A as Novel Susceptibility Genes for Coronary Artery Disease.Arterioscler Thromb Vasc Biol. 2018 Apr;38(4):964-975. doi: 10.1161/ATVBAHA.117.310594. Epub 2018 Feb 22.
18 Interstitial 1p32.1p32.3 deletion in a patient with multiple congenital anomalies.Am J Med Genet A. 2015 Oct;167A(10):2406-10. doi: 10.1002/ajmg.a.37178. Epub 2015 Jun 10.
19 Genome-Wide DNA Methylation Profiles of Phlegm-Dampness Constitution.Cell Physiol Biochem. 2018;45(5):1999-2008. doi: 10.1159/000487976. Epub 2018 Mar 2.
20 Reelin regulates neuronal progenitor migration in intact and epileptic hippocampus.J Neurosci. 2007 Feb 21;27(8):1803-11. doi: 10.1523/JNEUROSCI.3111-06.2007.
21 Design principles of concentration-dependent transcriptome deviations in drug-exposed differentiating stem cells. Chem Res Toxicol. 2014 Mar 17;27(3):408-20.
22 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.
23 Multiple microRNAs function as self-protective modules in acetaminophen-induced hepatotoxicity in humans. Arch Toxicol. 2018 Feb;92(2):845-858.
24 Identification of novel low-dose bisphenol a targets in human foreskin fibroblast cells derived from hypospadias patients. PLoS One. 2012;7(5):e36711. doi: 10.1371/journal.pone.0036711. Epub 2012 May 4.
25 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
26 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.
27 DNA methylome-wide alterations associated with estrogen receptor-dependent effects of bisphenols in breast cancer. Clin Epigenetics. 2019 Oct 10;11(1):138. doi: 10.1186/s13148-019-0725-y.
28 Identification of a transcriptomic signature of food-relevant genotoxins in human HepaRG hepatocarcinoma cells. Food Chem Toxicol. 2020 Jun;140:111297. doi: 10.1016/j.fct.2020.111297. Epub 2020 Mar 28.
29 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.
30 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.