Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTOC9876)

DOT Name Paired box protein Pax-6 (PAX6)
Synonyms Aniridia type II protein; Oculorhombin
Gene Name PAX6
Related Disease
Aniridia 1 ( )
Aniridia-cerebellar ataxia-intellectual disability syndrome ( )
Autosomal dominant keratitis ( )
Coloboma of optic nerve ( )
Foveal hypoplasia 1 ( )
Isolated optic nerve hypoplasia ( )
PAX6-related ocular dysgenesis ( )
Peters anomaly ( )
Smith-Lemli-Opitz syndrome ( )
Acquired nystagmus ( )
Adult glioblastoma ( )
Anxiety ( )
Autism ( )
Cataract 20 multiple types ( )
Coloboma, ocular, autosomal dominant ( )
Congenital glaucoma ( )
Congenital nervous system disorder ( )
Disorder of orbital region ( )
Gastric cancer ( )
Intellectual disability ( )
Isolated congenital microcephaly ( )
Melanoma ( )
Neoplasm ( )
Non-small-cell lung cancer ( )
Obesity ( )
Pathologic nystagmus ( )
Prostate neoplasm ( )
Ptosis ( )
Schizophrenia ( )
Type-1/2 diabetes ( )
Advanced cancer ( )
Axenfeld-Rieger syndrome type 1 ( )
Breast carcinoma ( )
Glioblastoma multiforme ( )
Foveal hypoplasia-presenile cataract syndrome ( )
Isolated aniridia ( )
Retinoblastoma ( )
Cataract ( )
Gastric neoplasm ( )
Glaucoma/ocular hypertension ( )
Hereditary diffuse gastric adenocarcinoma ( )
Juvenile open angle glaucoma ( )
Keratitis ( )
Non-insulin dependent diabetes ( )
Prostate cancer ( )
UniProt ID
PAX6_HUMAN
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
PDB ID
2CUE; 6PAX
Pfam ID
PF00046 ; PF00292
Sequence
MQNSHSGVNQLGGVFVNGRPLPDSTRQKIVELAHSGARPCDISRILQVSNGCVSKILGRY
YETGSIRPRAIGGSKPRVATPEVVSKIAQYKRECPSIFAWEIRDRLLSEGVCTNDNIPSV
SSINRVLRNLASEKQQMGADGMYDKLRMLNGQTGSWGTRPGWYPGTSVPGQPTQDGCQQQ
EGGGENTNSISSNGEDSDEAQMRLQLKRKLQRNRTSFTQEQIEALEKEFERTHYPDVFAR
ERLAAKIDLPEARIQVWFSNRRAKWRREEKLRNQRRQASNTPSHIPISSSFSTSVYQPIP
QPTTPVSSFTSGSMLGRTDTALTNTYSALPPMPSFTMANNLPMQPPVPSQTSSYSCMLPT
SPSVNGRSYDTYTPPHMQTHMNSQPMGTSGTTSTGLISPGVSVPVQVPGSEPDMSQYWPR
LQ
Function
Transcription factor with important functions in the development of the eye, nose, central nervous system and pancreas. Required for the differentiation of pancreatic islet alpha cells. Competes with PAX4 in binding to a common element in the glucagon, insulin and somatostatin promoters. Regulates specification of the ventral neuron subtypes by establishing the correct progenitor domains. Acts as a transcriptional repressor of NFATC1-mediated gene expression.
Tissue Specificity .Expressed in lymphoblasts.; [Isoform 5a]: Weakly expressed in lymphoblasts.
KEGG Pathway
Sig.ling pathways regulating pluripotency of stem cells (hsa04550 )
Maturity onset diabetes of the young (hsa04950 )
Reactome Pathway
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1) (R-HSA-381771 )
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP) (R-HSA-400511 )
Activation of anterior HOX genes in hindbrain development during early embryogenesis (R-HSA-5617472 )
Formation of the anterior neural plate (R-HSA-9823739 )
Regulation of gene expression in beta cells (R-HSA-210745 )

Molecular Interaction Atlas (MIA) of This DOT

45 Disease(s) Related to This DOT
Disease Name Disease ID Evidence Level Mode of Inheritance REF
Aniridia 1 DISZ95YB Definitive Autosomal dominant [1]
Aniridia-cerebellar ataxia-intellectual disability syndrome DIS4QZ3S Definitive Autosomal dominant [1]
Autosomal dominant keratitis DIS7T822 Definitive Autosomal dominant [2]
Coloboma of optic nerve DISR9DCH Definitive Autosomal dominant [3]
Foveal hypoplasia 1 DISU1634 Definitive Autosomal dominant [4]
Isolated optic nerve hypoplasia DISFFR14 Definitive Autosomal dominant [3]
PAX6-related ocular dysgenesis DISKX7OJ Definitive Autosomal dominant [5]
Peters anomaly DISERK0M Definitive Autosomal dominant [6]
Smith-Lemli-Opitz syndrome DISX9ZUA Definitive Biomarker [7]
Acquired nystagmus DISMYF5H Strong Biomarker [8]
Adult glioblastoma DISVP4LU Strong Altered Expression [9]
Anxiety DISIJDBA Strong Genetic Variation [10]
Autism DISV4V1Z Strong Altered Expression [11]
Cataract 20 multiple types DISN0IHS Strong Biomarker [12]
Coloboma, ocular, autosomal dominant DISRCFVW Strong Autosomal dominant [13]
Congenital glaucoma DISHN3GO Strong Altered Expression [14]
Congenital nervous system disorder DIS2BIP8 Strong Biomarker [15]
Disorder of orbital region DISH0ECJ Strong Biomarker [16]
Gastric cancer DISXGOUK Strong Biomarker [17]
Intellectual disability DISMBNXP Strong Genetic Variation [18]
Isolated congenital microcephaly DISUXHZ6 Strong Biomarker [19]
Melanoma DIS1RRCY Strong Biomarker [20]
Neoplasm DISZKGEW Strong Biomarker [21]
Non-small-cell lung cancer DIS5Y6R9 Strong Altered Expression [22]
Obesity DIS47Y1K Strong Genetic Variation [23]
Pathologic nystagmus DIS1QSPO Strong Genetic Variation [24]
Prostate neoplasm DISHDKGQ Strong Biomarker [25]
Ptosis DISJZNIY Strong Genetic Variation [26]
Schizophrenia DISSRV2N Strong Biomarker [27]
Type-1/2 diabetes DISIUHAP Strong Autosomal dominant [28]
Advanced cancer DISAT1Z9 moderate Genetic Variation [29]
Axenfeld-Rieger syndrome type 1 DISCJK7U moderate Biomarker [30]
Breast carcinoma DIS2UE88 moderate Biomarker [31]
Glioblastoma multiforme DISK8246 moderate Altered Expression [9]
Foveal hypoplasia-presenile cataract syndrome DIS9XKHS Supportive Autosomal dominant [4]
Isolated aniridia DISPEZG6 Supportive Autosomal dominant [32]
Retinoblastoma DISVPNPB Disputed Biomarker [33]
Cataract DISUD7SL Limited Genetic Variation [12]
Gastric neoplasm DISOKN4Y Limited Biomarker [34]
Glaucoma/ocular hypertension DISLBXBY Limited Biomarker [35]
Hereditary diffuse gastric adenocarcinoma DISUIBYS Limited Biomarker [34]
Juvenile open angle glaucoma DISZ43T5 Limited Altered Expression [14]
Keratitis DISMFOEI Limited Genetic Variation [36]
Non-insulin dependent diabetes DISK1O5Z Limited Genetic Variation [37]
Prostate cancer DISF190Y Limited Biomarker [25]
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⏷ Show the Full List of 45 Disease(s)
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DOT
30 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 Paired box protein Pax-6 (PAX6). [38]
Ciclosporin DMAZJFX Approved Ciclosporin increases the expression of Paired box protein Pax-6 (PAX6). [39]
Tretinoin DM49DUI Approved Tretinoin decreases the expression of Paired box protein Pax-6 (PAX6). [40]
Doxorubicin DMVP5YE Approved Doxorubicin increases the expression of Paired box protein Pax-6 (PAX6). [41]
Decitabine DMQL8XJ Approved Decitabine increases the expression of Paired box protein Pax-6 (PAX6). [34]
Marinol DM70IK5 Approved Marinol decreases the expression of Paired box protein Pax-6 (PAX6). [43]
Fluorouracil DMUM7HZ Approved Fluorouracil decreases the expression of Paired box protein Pax-6 (PAX6). [44]
Panobinostat DM58WKG Approved Panobinostat decreases the expression of Paired box protein Pax-6 (PAX6). [45]
Dexamethasone DMMWZET Approved Dexamethasone increases the expression of Paired box protein Pax-6 (PAX6). [46]
Folic acid DMEMBJC Approved Folic acid decreases the expression of Paired box protein Pax-6 (PAX6). [46]
Isotretinoin DM4QTBN Approved Isotretinoin increases the expression of Paired box protein Pax-6 (PAX6). [47]
Cytarabine DMZD5QR Approved Cytarabine increases the expression of Paired box protein Pax-6 (PAX6). [48]
Alitretinoin DMME8LH Approved Alitretinoin decreases the expression of Paired box protein Pax-6 (PAX6). [49]
Thalidomide DM70BU5 Approved Thalidomide increases the expression of Paired box protein Pax-6 (PAX6). [47]
Phenytoin DMNOKBV Approved Phenytoin increases the expression of Paired box protein Pax-6 (PAX6). [47]
Nilotinib DM7HXWT Approved Nilotinib increases the expression of Paired box protein Pax-6 (PAX6). [47]
Abacavir DMMN36E Approved Abacavir increases the expression of Paired box protein Pax-6 (PAX6). [47]
Dabigatran DMDI6R4 Approved Dabigatran increases the expression of Paired box protein Pax-6 (PAX6). [47]
Ramelteon DM7IW9J Approved Ramelteon decreases the expression of Paired box protein Pax-6 (PAX6). [47]
Urethane DM7NSI0 Phase 4 Urethane increases the expression of Paired box protein Pax-6 (PAX6). [50]
SNDX-275 DMH7W9X Phase 3 SNDX-275 decreases the expression of Paired box protein Pax-6 (PAX6). [45]
Fenretinide DMRD5SP Phase 3 Fenretinide decreases the expression of Paired box protein Pax-6 (PAX6). [51]
Benzo(a)pyrene DMN7J43 Phase 1 Benzo(a)pyrene decreases the expression of Paired box protein Pax-6 (PAX6). [52]
CHIR-99021 DMB8MNU Patented CHIR-99021 increases the expression of Paired box protein Pax-6 (PAX6). [47]
Trichostatin A DM9C8NX Investigative Trichostatin A decreases the expression of Paired box protein Pax-6 (PAX6). [38]
Paraquat DMR8O3X Investigative Paraquat decreases the expression of Paired box protein Pax-6 (PAX6). [54]
Glyphosate DM0AFY7 Investigative Glyphosate affects the expression of Paired box protein Pax-6 (PAX6). [55]
Chlorpyrifos DMKPUI6 Investigative Chlorpyrifos decreases the expression of Paired box protein Pax-6 (PAX6). [56]
SAG DMHOG7W Investigative SAG increases the expression of Paired box protein Pax-6 (PAX6). [57]
CHIR-98014 DMVEBT6 Investigative CHIR-98014 decreases the expression of Paired box protein Pax-6 (PAX6). [38]
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⏷ Show the Full List of 30 Drug(s)
1 Drug(s) Affected the Post-Translational Modifications of This DOT
Drug Name Drug ID Highest Status Interaction REF
Bisphenol A DM2ZLD7 Investigative Bisphenol A increases the methylation of Paired box protein Pax-6 (PAX6). [53]
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References

1 A de novo nonsense mutation of PAX6 gene in a patient with aniridia, ataxia, and mental retardation. Am J Med Genet A. 2007 Aug 1;143A(15):1802-5. doi: 10.1002/ajmg.a.31808.
2 Mutation of the PAX6 gene in patients with autosomal dominant keratitis. Am J Hum Genet. 1995 Sep;57(3):539-48.
3 Mutations of the PAX6 gene detected in patients with a variety of optic-nerve malformations. Am J Hum Genet. 2003 Jun;72(6):1565-70. doi: 10.1086/375555. Epub 2003 Apr 29.
4 Missense mutations in the most ancient residues of the PAX6 paired domain underlie a spectrum of human congenital eye malformations. Hum Mol Genet. 1999 Feb;8(2):165-72. doi: 10.1093/hmg/8.2.165.
5 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.
6 Flexible and scalable diagnostic filtering of genomic variants using G2P with Ensembl VEP. Nat Commun. 2019 May 30;10(1):2373. doi: 10.1038/s41467-019-10016-3.
7 Absence of ventral cell populations in the developing brain in a rat model of the Smith-Lemli-Opitz syndrome.Am J Med Genet. 1999 Nov 26;87(3):207-16. doi: 10.1002/(sici)1096-8628(19991126)87:3<207::aid-ajmg3>3.0.co;2-5.
8 A family with a mild form of congenital nystagmus and optic disc coloboma caused by a novel PAX6 mutation.Gene. 2019 Jul 15;705:177-180. doi: 10.1016/j.gene.2019.04.035. Epub 2019 Apr 12.
9 MicroRNA-365 suppressed cell proliferation and migration via targeting PAX6 in glioblastoma.Am J Transl Res. 2019 Jan 15;11(1):361-369. eCollection 2019.
10 Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.Nat Genet. 2018 Jul;50(7):920-927. doi: 10.1038/s41588-018-0151-7. Epub 2018 Jun 25.
11 Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome.Cortex. 2013 Nov-Dec;49(10):2700-10. doi: 10.1016/j.cortex.2013.02.009. Epub 2013 Feb 19.
12 Two Paired Box 6 mutations identified in Chinese patients with classic congenital aniridia and cataract.Mol Med Rep. 2018 Nov;18(5):4439-4445. doi: 10.3892/mmr.2018.9469. Epub 2018 Sep 10.
13 Recurrent heterozygous PAX6 missense variants cause severe bilateral microphthalmia via predictable effects on DNA-protein interaction. Genet Med. 2020 Mar;22(3):598-609. doi: 10.1038/s41436-019-0685-9. Epub 2019 Nov 8.
14 Reduced expression of Pax6 in lens and cornea of mutant mice leads to failure of chamber angle development and juvenile glaucoma.Hum Mol Genet. 2010 Sep 1;19(17):3332-42. doi: 10.1093/hmg/ddq237. Epub 2010 Jun 10.
15 In vivo MRI of altered brain anatomy and fiber connectivity in adult pax6 deficient mice.Cereb Cortex. 2009 Dec;19(12):2838-47. doi: 10.1093/cercor/bhp057. Epub 2009 Mar 27.
16 From eyeless to neurological diseases.Exp Eye Res. 2017 Mar;156:5-9. doi: 10.1016/j.exer.2015.11.006. Epub 2015 Nov 22.
17 miRNA and mRNA expression profiles in gastric cancer patients and the relationship with circRNA.Neoplasma. 2019 Jun 29;66(6):879-886. doi: 10.4149/neo_2018_181211N952. Print 2019 Nov.
18 The genetic architecture of aniridia and Gillespie syndrome.Hum Genet. 2019 Sep;138(8-9):881-898. doi: 10.1007/s00439-018-1934-8. Epub 2018 Sep 22.
19 A critical role of Pax6 in alcohol-induced fetal microcephaly.Neurobiol Dis. 2004 Jul;16(2):370-6. doi: 10.1016/j.nbd.2004.03.004.
20 Silencing of Peroxiredoxin 2 and aberrant methylation of 33 CpG islands in putative promoter regions in human malignant melanomas.Cancer Res. 2006 Jun 15;66(12):6080-6. doi: 10.1158/0008-5472.CAN-06-0157.
21 Downregulated Pancreatic Beta Cell Genes Indicate Poor Prognosis in Patients With Pancreatic Neuroendocrine Neoplasms.Ann Surg. 2020 Apr;271(4):732-739. doi: 10.1097/SLA.0000000000002911.
22 The PAX6-ZEB2 axis promotes metastasis and cisplatin resistance in non-small cell lung cancer through PI3K/AKT signaling.Cell Death Dis. 2019 Apr 25;10(5):349. doi: 10.1038/s41419-019-1591-4.
23 The modifier effect of the BDNF gene in the phenotype of the WAGRO syndrome.Gene. 2013 Mar 10;516(2):285-90. doi: 10.1016/j.gene.2012.11.073. Epub 2012 Dec 21.
24 A novel mutation of PAX6 identified in a Chinese twin family with congenital aniridia complicated with nystagmus.Genet Mol Res. 2014 Oct 27;13(4):8679-85. doi: 10.4238/2014.October.27.8.
25 The long tail of oncogenic drivers in prostate cancer.Nat Genet. 2018 May;50(5):645-651. doi: 10.1038/s41588-018-0078-z. Epub 2018 Apr 2.
26 PAX6 mutation in association with ptosis, cataract, iris hypoplasia, corneal opacification and diabetes: a new variant of familial aniridia?.Clin Exp Ophthalmol. 2013 Dec;41(9):835-41. doi: 10.1111/ceo.12109. Epub 2013 May 3.
27 The effect of implementation intentions on prospective memory performance in patients with schizophrenia: A multinomial modeling approach.Schizophr Res. 2020 Jan;215:120-125. doi: 10.1016/j.schres.2019.11.003. Epub 2019 Nov 26.
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29 Epigenetically regulated PAX6 drives cancer cells toward a stem-like state via GLI-SOX2 signaling axis in lung adenocarcinoma.Oncogene. 2018 Nov;37(45):5967-5981. doi: 10.1038/s41388-018-0373-2. Epub 2018 Jul 6.
30 Novel identification of a four-base-pair deletion mutation in PITX2 in a Rieger syndrome family.J Dent Res. 2003 Dec;82(12):1008-12. doi: 10.1177/154405910308201214.
31 Identification of genes and pathways associated with MDR in MCF-7/MDR breast cancer cells by RNA-seq analysis.Mol Med Rep. 2018 May;17(5):6211-6226. doi: 10.3892/mmr.2018.8704. Epub 2018 Mar 7.
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33 MicroRNA-129-5p suppresses proliferation, migration and invasion of retinoblastoma cells through PI3K/AKT signaling pathway by targeting PAX6.Pathol Res Pract. 2019 Dec;215(12):152641. doi: 10.1016/j.prp.2019.152641. Epub 2019 Oct 4.
34 Chemical genomic screening for methylation-silenced genes in gastric cancer cell lines using 5-aza-2'-deoxycytidine treatment and oligonucleotide microarray. Cancer Sci. 2006 Jan;97(1):64-71.
35 Identification of genes involved in glaucoma pathogenesis using combined network analysis and empirical studies.Hum Mol Genet. 2019 Nov 1;28(21):3637-3663. doi: 10.1093/hmg/ddz222.
36 Microphthalmia, late onset keratitis, and iris coloboma/aniridia in a family with a novel PAX6 mutation.Ophthalmic Genet. 2012 Jun;33(2):119-21. doi: 10.3109/13816810.2011.642452. Epub 2011 Dec 15.
37 A common functional regulatory variant at a type 2 diabetes locus upregulates ARAP1 expression in the pancreatic beta cell.Am J Hum Genet. 2014 Feb 6;94(2):186-97. doi: 10.1016/j.ajhg.2013.12.011. Epub 2014 Jan 16.
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41 Gamma-irradiation and doxorubicin treatment of normal human cells cause cell cycle arrest via different pathways. Mol Cells. 2005 Dec 31;20(3):331-8.
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43 hiPSC-Based Model of Prenatal Exposure to Cannabinoids: Effect on Neuronal Differentiation. Front Mol Neurosci. 2020 Jul 6;13:119. doi: 10.3389/fnmol.2020.00119. eCollection 2020.
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50 Ethyl carbamate induces cell death through its effects on multiple metabolic pathways. Chem Biol Interact. 2017 Nov 1;277:21-32.
51 Fenretinide-induced neuronal differentiation of ARPE-19 human retinal pigment epithelial cells is associated with the differential expression of Hsp70, 14-3-3, pax-6, tubulin beta-III, NSE, and bag-1 proteins. Mol Vis. 2006 Nov 1;12:1355-63.
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53 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.
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55 Glyphosate-based herbicide induces long-lasting impairment in neuronal and glial differentiation. Environ Toxicol. 2022 Aug;37(8):2044-2057. doi: 10.1002/tox.23549. Epub 2022 Apr 29.
56 Chlorpyrifos inhibits neural induction via Mfn1-mediated mitochondrial dysfunction in human induced pluripotent stem cells. Sci Rep. 2017 Jan 23;7:40925. doi: 10.1038/srep40925.
57 Differential role of Pax6 and its interaction with Shh-Gli1-IDH2 axis in regulation of glioma growth and chemoresistance. J Biochem Mol Toxicol. 2023 Feb;37(2):e23241. doi: 10.1002/jbt.23241. Epub 2022 Oct 7.