Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTN42Y77)

DOT Name Dyslexia-associated protein KIAA0319 (KIAA0319)
Gene Name KIAA0319
Related Disease
Alzheimer disease ( )
Autism spectrum disorder ( )
Language disorder ( )
Lissencephaly spectrum disorders ( )
Schizophrenia ( )
Episodic kinesigenic dyskinesia 1 ( )
Nervous system disease ( )
Polycystic kidney disease ( )
UniProt ID
K0319_HUMAN
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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PDB ID
2E7M
Pfam ID
PF18911
Sequence
MAPPTGVLSSLLLLVTIAGCARKQCSEGRTYSNAVISPNLETTRIMRVSHTFPVVDCTAA
CCDLSSCDLAWWFEGRCYLVSCPHKENCEPKKMGPIRSYLTFVLRPVQRPAQLLDYGDMM
LNRGSPSGIWGDSPEDIRKDLTFLGKDWGLEEMSEYSDDYRELEKDLLQPSGKQEPRGSA
EYTDWGLLPGSEGAFNSSVGDSPAVPAETQQDPELHYLNESASTPAPKLPERSVLLPLPT
TPSSGEVLEKEKASQLQEQSSNSSGKEVLMPSHSLPPASLELSSVTVEKSPVLTVTPGST
EHSIPTPPTSAAPSESTPSELPISPTTAPRTVKELTVSAGDNLIITLPDNEVELKAFVAP
APPVETTYNYEWNLISHPTDYQGEIKQGHKQTLNLSQLSVGLYVFKVTVSSENAFGEGFV
NVTVKPARRVNLPPVAVVSPQLQELTLPLTSALIDGSQSTDDTEIVSYHWEEINGPFIEE
KTSVDSPVLRLSNLDPGNYSFRLTVTDSDGATNSTTAALIVNNAVDYPPVANAGPNHTIT
LPQNSITLNGNQSSDDHQIVLYEWSLGPGSEGKHVVMQGVQTPYLHLSAMQEGDYTFQLK
VTDSSRQQSTAVVTVIVQPENNRPPVAVAGPDKELIFPVESATLDGSSSSDDHGIVFYHW
EHVRGPSAVEMENIDKAIATVTGLQVGTYHFRLTVKDQQGLSSTSTLTVAVKKENNSPPR
ARAGGRHVLVLPNNSITLDGSRSTDDQRIVSYLWIRDGQSPAAGDVIDGSDHSVALQLTN
LVEGVYTFHLRVTDSQGASDTDTATVEVQPDPRKSGLVELTLQVGVGQLTEQRKDTLVRQ
LAVLLNVLDSDIKVQKIRAHSDLSTVIVFYVQSRPPFKVLKAAEVARNLHMRLSKEKADF
LLFKVLRVDTAGCLLKCSGHGHCDPLTKRCICSHLWMENLIQRYIWDGESNCEWSIFYVT
VLAFTLIVLTGGFTWLCICCCKRQKRTKIRKKTKYTILDNMDEQERMELRPKYGIKHRST
EHNSSLMVSESEFDSDQDTIFSREKMERGNPKVSMNGSIRNGASFSYCSKDR
Function
Involved in neuronal migration during development of the cerebral neocortex. May function in a cell autonomous and a non-cell autonomous manner and play a role in appropriate adhesion between migrating neurons and radial glial fibers. May also regulate growth and differentiation of dendrites.
Tissue Specificity Detected in adult brain cortex and fetal frontal lobe (at protein level). Highly expressed in brain cortex, putamen, amygdala, hippocampus and cerebellum.
Reactome Pathway
Clathrin-mediated endocytosis (R-HSA-8856828 )
Cargo recognition for clathrin-mediated endocytosis (R-HSA-8856825 )

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Alzheimer disease DISF8S70 Strong Altered Expression [1]
Autism spectrum disorder DISXK8NV Strong Biomarker [2]
Language disorder DISTLKP7 Strong Biomarker [3]
Lissencephaly spectrum disorders DISBCZL7 Strong Genetic Variation [4]
Schizophrenia DISSRV2N Strong Biomarker [5]
Episodic kinesigenic dyskinesia 1 DISGVQMP Limited Genetic Variation [6]
Nervous system disease DISJ7GGT Limited Biomarker [7]
Polycystic kidney disease DISWS3UY Limited Genetic Variation [6]
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⏷ Show the Full List of 8 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
7 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 Dyslexia-associated protein KIAA0319 (KIAA0319). [8]
Triclosan DMZUR4N Approved Triclosan decreases the expression of Dyslexia-associated protein KIAA0319 (KIAA0319). [9]
Troglitazone DM3VFPD Approved Troglitazone increases the expression of Dyslexia-associated protein KIAA0319 (KIAA0319). [10]
PMID28460551-Compound-2 DM4DOUB Patented PMID28460551-Compound-2 decreases the expression of Dyslexia-associated protein KIAA0319 (KIAA0319). [12]
Formaldehyde DM7Q6M0 Investigative Formaldehyde increases the expression of Dyslexia-associated protein KIAA0319 (KIAA0319). [13]
Sulforaphane DMQY3L0 Investigative Sulforaphane increases the expression of Dyslexia-associated protein KIAA0319 (KIAA0319). [14]
Acetaldehyde DMJFKG4 Investigative Acetaldehyde decreases the expression of Dyslexia-associated protein KIAA0319 (KIAA0319). [15]
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⏷ Show the Full List of 7 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene affects the methylation of Dyslexia-associated protein KIAA0319 (KIAA0319). [11]
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References

1 microRNA-592 blockade inhibits oxidative stress injury in Alzheimer's disease astrocytes via the KIAA0319-mediated Keap1/Nrf2/ARE signaling pathway.Exp Neurol. 2020 Feb;324:113128. doi: 10.1016/j.expneurol.2019.113128. Epub 2019 Nov 21.
2 Unmasking a novel disease gene NEO1 associated with autism spectrum disorders by a hemizygous deletion on chromosome 15 and a functional polymorphism.Behav Brain Res. 2016 Mar 1;300:135-42. doi: 10.1016/j.bbr.2015.10.041. Epub 2015 Oct 27.
3 DCDC2, KIAA0319 and CMIP are associated with reading-related traits.Biol Psychiatry. 2011 Aug 1;70(3):237-45. doi: 10.1016/j.biopsych.2011.02.005. Epub 2011 Mar 31.
4 Cytoskeleton in action: lissencephaly, a neuronal migration disorder.Wiley Interdiscip Rev Dev Biol. 2013 Mar-Apr;2(2):229-45. doi: 10.1002/wdev.67.
5 Genetic influences of resting state fMRI activity in language-related brain regions in healthy controls and schizophrenia patients: a pilot study.Brain Imaging Behav. 2013 Mar;7(1):15-27. doi: 10.1007/s11682-012-9168-1.
6 Adeno-associated virus 2 bound to its cellular receptor AAVR.Nat Microbiol. 2019 Apr;4(4):675-682. doi: 10.1038/s41564-018-0356-7. Epub 2019 Feb 11.
7 Exploring the transcriptome of ciliated cells using in silico dissection of human tissues.PLoS One. 2012;7(4):e35618. doi: 10.1371/journal.pone.0035618. Epub 2012 Apr 25.
8 Stem cell transcriptome responses and corresponding biomarkers that indicate the transition from adaptive responses to cytotoxicity. Chem Res Toxicol. 2017 Apr 17;30(4):905-922.
9 Transcriptome and DNA methylome dynamics during triclosan-induced cardiomyocyte differentiation toxicity. Stem Cells Int. 2018 Oct 29;2018:8608327.
10 Effects of ciglitazone and troglitazone on the proliferation of human stomach cancer cells. World J Gastroenterol. 2009 Jan 21;15(3):310-20.
11 Effect of aflatoxin B(1), benzo[a]pyrene, and methapyrilene on transcriptomic and epigenetic alterations in human liver HepaRG cells. Food Chem Toxicol. 2018 Nov;121:214-223. doi: 10.1016/j.fct.2018.08.034. Epub 2018 Aug 26.
12 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.
13 Regulation of chromatin assembly and cell transformation by formaldehyde exposure in human cells. Environ Health Perspect. 2017 Sep 21;125(9):097019.
14 Transcriptome and DNA methylation changes modulated by sulforaphane induce cell cycle arrest, apoptosis, DNA damage, and suppression of proliferation in human liver cancer cells. Food Chem Toxicol. 2020 Feb;136:111047. doi: 10.1016/j.fct.2019.111047. Epub 2019 Dec 12.
15 Transcriptome profile analysis of saturated aliphatic aldehydes reveals carbon number-specific molecules involved in pulmonary toxicity. Chem Res Toxicol. 2014 Aug 18;27(8):1362-70.