PAX6 (paired box 6)
2009-08-01 Yi-Hong Zhou AffiliationDepartment of Neurological Surgery, Department of Biological Chemistry (joint), University of California, Irvine, Med Sci I, Room C214, Irvine, CA 92697, USA
Identity
HGNC
LOCATION
11p13
LOCUSID
ALIAS
AN,AN1,AN2,ASGD5,D11S812E,FVH1,MGDA,WAGR
FUSION GENES
DNA/RNA
Description
The PAX6 coding region extends over a genomic interval of 16-17 kb and comprise 10 (isoform a) and 11 exons (isoform b).
Transcription
Three transcripts have been identified, originating from alternative promoter usage (variant 3) or alternative splicing (variant 2, additional in-frame coding 42 bp exon downstream of exon 5 of variant 1); transcription is from centromere to telomere.
Proteins
There are two isoforms of PAX6, PAX6a and PAX6b with additional 14 extra amino acids in the paired box DNA binding domain. PAX6a, 423 amino acids, ~47 kDa; PAX6b, 436 amino acids, ~49 kDa.
Description
PAX6 belongs to the paired box family of transcription factors, contains two DNA binding domains, a paired box (PD) and a paired-type homeodomain (HD), and a carboxyl-terminal transactivation domain rich of proline, serine, and threonine (PST).
Expression
PAX6, predominately in form of PAX6a, is expressed in the developing sensory organs (including eye, nasal and olfactory tissues), central nervous system (including forebrain, hindbrain, and spinal cord), and endocrine system (including anterior pituitary gland and pancreas) in human and rodent (Walther and Gruss., 1991; Stoykova and Gruss., 1994; Davis and Reed., 1996; Terzic and Saraga-Babic., 1999; Pinson et al., 2005). PAX6 expression is sustained into adulthood in certain areas of the brain, including, hippocampal dentate gyrus (Maekawa et al., 2005; Nacher et al., 2005), ependymal layer and the subventricular zone of the lateral ventricle (Hack et al., 2005; Kohwi et al., 2005), radial glia-like cells (Gubert et al., 2009), and in mature endocrine cells in pancreas (St-Onge et al., 1997). PAX6 transcription is regulated by two promoters, P0 and P1, which are remarkably conserved in evolution in both of their nucleotide sequence arrangement and functional control of special and temporal expression of PAX6 in development (Xu and Saunders, 1997; Okladnova et al., 1998a; Williams et al., 1998; Xu and Saunders, 1998; Kammandel et al., 1999; Plaza et al., 1999a; Xu et al., 1999; Tyas et al., 2006), involving multiple transcription factors, such as POU factor Brn-3B, TFCP2, SP1, the basic helix-loop-helix transcription factor NeuroD/BETA2, CCCTC binding factor CTCF, PPARgamma (Plaza et al., 1999b; Zheng et al., 2001; Schinner et al., 2002; Marsich et al., 2003; Li et al., 2006; Wu et al., 2006). PAX6 expression is also regulated by a long range downstream enhancer (Kleinjan et al., 2006) and is under autoregulation (Grocott et al., 2007) and post modification by HIPK2 and protein phosphatase 1 (Kim et al., 2006; Yan et al., 2007). A promoter-associated polymorphic repeat was found to modulate PAX6 expression in human brain (Okladnova et al., 1998b).
Localisation
Nuclear.
Function
Loss of Pax6 function in rodent mutant and knock-out model revealed that Pax6 is a key regulator of a multitude of developmental processes of sensory system, including eye, nasal and olfactory (Hill et al., 1991; Grindley et al., 1995; Quinn et al., 1996; van Raamsdonk and Tilghman, 2000; Singh et al., 2002; van Heyningen and Williamson, 2002; Collinson et al., 2003; Davis et al., 2003; Brill et al., 2008), CNS (Matsuo et al., 1993; Schmahl et al., 1993; Stoykova et al., 1996; Grindley et al., 1997; Osumi et al., 1997; Mastick et al., 1997; Warren and Price, 1997; Gotz et al., 1998; Sun et al., 1998; Engelkamp et al., 1999; Kawano et al., 1999; Pratt et al., 2000; Stoykova et al., 2000; Estivill-Torrus et al., 2002; Pratt et al., 2002; Talamillo et al., 2003; Quinn et al., 2007), pituitary (Bentley et al., 1999; Kioussi et al., 1999) and pancreas (Sander et al., 1997; St-Onge et al., 1997; Dohrmann et al., 2000; Zhang et al., 2003). Pax6 function in development of fundamental sensory processes and central nervous system, particularly of the photoreceptive organ, are remarkably conserved in evolution (Halder et al., 1995; Gehring et al., 2005). PAX6 funciton in development were found to be under control of Shh, notch and EGFR signaling (Ericson et al., 1997; Kumar and Moses, 2001; Onuma et al., 2002; Li and Lu, 2005), essential for neural stem cell proliferation, multipotency, and neurogenesis in many regions of the central nervous system (Warren et al., 1999; Bishop et al., 2000; Toresson et al., 2000; Marquardt et al., 2001; Yamasaki et al., 2001; Yun et al., 2001; Estivill-Torrus et al., 2002; Heins et al., 2002; Simpson and Price, 2002; Tyas et al., 2003; Collinson et al., 2004; Haubst et al., 2004; Nomura and Osumi, 2004; Schuurmans et al., 2004; Maekawa et al., 2005; Bel-Vialar et al., 2007; Duparc et al., 2007; Quinn et al., 2007; Canto-Soler et al., 2008; Oron-Karni et al., 2008; Osumi et al., 2008), and appears to control the balance between neural stem cell self-renewal and neurogenesis under a dose-dependent manner (Sansom et al., 2009).
PAX6 binds as a monomer to relatively long (15-22 bp) DNA binding sites, and the 14 aa insertion in the paired domain allows different binding affinity to DNA sequences between PAX6a and PAX6b (Epstein et al., 1994a; Epstein et al., 1994b). Through binding to different DNA sequences via usage of various DNA binding motifs alone or in combination, PAX6 controls the expression of various downstream target genes involved in complex gene regulatory networks for cell proliferation, adhesion, migration, and neurogenesis (Schmahl et al., 1993; Caric et al., 1997; Sander et al., 1997; Sax et al., 1997; Tang et al., 1997; Duncan et al., 1998; Beimesche et al., 1999; Meech et al., 1999; Singh et al., 2000; Sivak et al., 2000; Zhou et al., 2000; Chauhan et al., 2002; Mishra et al., 2002; Skala-Rubinson et al., 2002; Zhou et al., 2002; Andrews and Mastick, 2003; Davis et al., 2003; Horie et al., 2003; Tyas et al., 2003; Cvekl et al., 2004; Grinchuk et al., 2005; Mayes et al., 2006; Holm et al., 2007; Tuoc and Stoykova, 2008). Not only reduced, but also increases level of PAX6 gene dosage also cause defects in developmental processes that are sensitive to PAX6 dosage, including eye organogenesis and corticogenesis (Schedl et al., 1996; Berger et al., 2007; Manuel et al., 2007).
PAX6 binds as a monomer to relatively long (15-22 bp) DNA binding sites, and the 14 aa insertion in the paired domain allows different binding affinity to DNA sequences between PAX6a and PAX6b (Epstein et al., 1994a; Epstein et al., 1994b). Through binding to different DNA sequences via usage of various DNA binding motifs alone or in combination, PAX6 controls the expression of various downstream target genes involved in complex gene regulatory networks for cell proliferation, adhesion, migration, and neurogenesis (Schmahl et al., 1993; Caric et al., 1997; Sander et al., 1997; Sax et al., 1997; Tang et al., 1997; Duncan et al., 1998; Beimesche et al., 1999; Meech et al., 1999; Singh et al., 2000; Sivak et al., 2000; Zhou et al., 2000; Chauhan et al., 2002; Mishra et al., 2002; Skala-Rubinson et al., 2002; Zhou et al., 2002; Andrews and Mastick, 2003; Davis et al., 2003; Horie et al., 2003; Tyas et al., 2003; Cvekl et al., 2004; Grinchuk et al., 2005; Mayes et al., 2006; Holm et al., 2007; Tuoc and Stoykova, 2008). Not only reduced, but also increases level of PAX6 gene dosage also cause defects in developmental processes that are sensitive to PAX6 dosage, including eye organogenesis and corticogenesis (Schedl et al., 1996; Berger et al., 2007; Manuel et al., 2007).
Homology
PAX6 shares homology through the conserved paired box domain with the other members of the nine PAX gene family.
Mutations
Germinal
Heterozygous intragenic mutation of PAX6, that causes loss of function of one copy of the PAX6 gene, is the cause of aniridia syndrome (Ton et al., 1991; Glaser et al., 1992; Prosser and van Heyningen, 1998; Robinson et al., 2008; Hingorani et al., 2009; MRC Human Genetics Unit) and cerebral malformation, olfactory dysfunction, absence of the pineal gland and unilateral polymicrogyria (Sisodiya et al., 2001; Free et al., 2003; Mitchell et al., 2003; Bamiou et al., 2007a; Bamiou et al., 2007b).
PAX6 3 deletion also results in aniridia, autism and mental retardation (Davis et al., 2008).
PAX6 3 deletion also results in aniridia, autism and mental retardation (Davis et al., 2008).
Implicated in
Entity name
Brain cancer
Note
The expression level of PAX6 in human glioma cell lines was shown to be negatively associated with the degree of tumorigenicity. PAX6 expression level is lower in glioblastoma compared to the adjacent normal tissue and to the anaplastic astrocytoma previously formed in the same patient (Zhou et al., 2003). Ectopic expression of PAX6 in glioma cell lines suppressed cell anchorage independent growth, ability to survive under oxidative stress induced by cell detachment, ability to invade partially by suppression of MMP2 gene expression, ability to induce angiogenesis by initiating a new signaling pathway independent of PI3K/Akt-HIF1A signaling to suppress VEGFA, and overall tumor growth after intracranial implantation in immunocompromised mouse brain (Zhou et al., 2005; Mayes et al., 2006; Chang et al., 2007; Zhou et al., 2009). Mutation analysis for PAX6 in gliomas failed to identify PAX6 mutation in its coding and regulating regions, suggesting involvement of epigenetic mechanisms in the silencing of PAX6 in glioma (Pinto et al., 2007). PAX6 expression is activated in glioma cell line with re-introduction of a normal ch.10, suggesting that PAX6 is regulated by a gene(s) on ch.10 (Zhou et al., 2005).
Prognosis
PAX6 is a factor related to a longer survival prognosis for astrocytic gliomas (Zhou et al., 2003).
Entity name
Pancreatic cancer
Note
PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation (Lang et al., 2008). In pancreatic carcinoma cell lines, PAX6 bind directly to an enhancer element in the MET promoter and activate the expression of the MET gene (Mascarenhas et al., 2009).
Entity name
Bladder cancer
Note
Methylation of PAX6-promoters is increased in early bladder cancer and in normal mucosa adjacent to pTa tumours (Hellwinkel et al., 2008).
Entity name
Familial adenomatous polyposis (FAP) related carcinoma
Note
PAX6 gene is methylated in FAP-related carcinoma. Patients with familial adenomatous polyposis (FAP) have a high risk of developing duodenal carcinomas (Berkhout et al., 2007).
Entity name
Note
WAGR syndrome can have aniridia due to deletion of chromosome 11 including PAX6 (Gronskov et al., 2001; Chao et al., 2003). However, PAX6 mutation is only found in aniridia patient, not WAGR syndrome associated anomalies (Robinson et al., 2008).
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 14586016 | 2003 | R-cadherin is a Pax6-regulated, growth-promoting cue for pioneer axons. | Andrews GL et al |
| 17454233 | 2007 | Auditory and verbal working memory deficits in a child with congenital aniridia due to a PAX6 mutation. | Bamiou DE et al |
| 17485622 | 2007 | Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations. | Bamiou DE et al |
| 10319322 | 1999 | Tissue-specific transcriptional activity of a pancreatic islet cell-specific enhancer sequence/Pax6-binding site determined in normal adult tissues in vivo using transgenic mice. | Beimesche S et al |
| 17399698 | 2007 | The on/off of Pax6 controls the tempo of neuronal differentiation in the developing spinal cord. | Bel-Vialar S et al |
| 10451227 | 1999 | Pax6 is implicated in murine pituitary endocrine function. | Bentley CA et al |
| 17329367 | 2007 | Conditional activation of Pax6 in the developing cortex of transgenic mice causes progenitor apoptosis. | Berger J et al |
| 17873900 | 2007 | Chromosomal and methylation alterations in sporadic and familial adenomatous polyposis-related duodenal carcinomas. | Berkhout M et al |
| 10764649 | 2000 | Regulation of area identity in the mammalian neocortex by Emx2 and Pax6. | Bishop KM et al |
| 18562615 | 2008 | A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb. | Brill MS et al |
| 18224715 | 2008 | Transcription factors CTCF and Pax6 are segregated to different cell types during retinal cell differentiation. | Canto-Soler MV et al |
| 9362466 | 1997 | Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6. | Carić D et al |
| 17318412 | 2007 | PAX6 increases glioma cell susceptibility to detachment and oxidative stress. | Chang JY et al |
| 12552561 | 2003 | Missense mutations in the DNA-binding region and termination codon in PAX6. | Chao LY et al |
| 12485166 | 2002 | A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens. | Chauhan BK et al |
| 15037575 | 2004 | Corneal development, limbal stem cell function, and corneal epithelial cell migration in the Pax6(+/-) mouse. | Collinson JM et al |
| 15558475 | 2004 | Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens. | Cvekl A et al |
| 12692153 | 2003 | Requirement for Pax6 in corneal morphogenesis: a role in adhesion. | Davis J et al |
| 8756438 | 1996 | Role of Olf-1 and Pax-6 transcription factors in neurodevelopment. | Davis JA et al |
| 18322702 | 2008 | Pax6 3' deletion results in aniridia, autism and mental retardation. | Davis LK et al |
| 10704887 | 2000 | Pax genes and the differentiation of hormone-producing endocrine cells in the pancreas. | Dohrmann C et al |
| 9710641 | 1998 | Dual roles for Pax-6: a transcriptional repressor of lens fiber cell-specific beta-crystallin genes. | Duncan MK et al |
| 17157287 | 2007 | Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle. | Duparc RH et al |
| 10409504 | 1999 | Role of Pax6 in development of the cerebellar system. | Engelkamp D et al |
| 8132558 | 1994 | Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes. | Epstein J et al |
| 7958875 | 1994 | Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing. | Epstein JA et al |
| 9230312 | 1997 | Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling. | Ericson J et al |
| 11807037 | 2002 | Pax6 is required to regulate the cell cycle and the rate of progression from symmetrical to asymmetrical division in mammalian cortical progenitors. | Estivill-Torrus G et al |
| 14683729 | 2003 | Quantitative MR image analysis in subjects with defects in the PAX6 gene. | Free SL et al |
| 15653558 | 2005 | New perspectives on eye development and the evolution of eyes and photoreceptors. | Gehring WJ et al |
| 1345175 | 1992 | Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene. | Glaser T et al |
| 9856459 | 1998 | Pax6 controls radial glia differentiation in the cerebral cortex. | Götz M et al |
| 16115881 | 2005 | The Optimedin gene is a downstream target of Pax6. | Grinchuk O et al |
| 9232602 | 1997 | Disruption of PAX6 function in mice homozygous for the Pax6Sey-1Neu mutation produces abnormalities in the early development and regionalization of the diencephalon. | Grindley JC et al |
| 17251190 | 2007 | The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter. | Grocott T et al |
| 11479730 | 2001 | Population-based risk estimates of Wilms tumor in sporadic aniridia. A comprehensive mutation screening procedure of PAX6 identifies 80% of mutations in aniridia. | Grønskov K et al |
| 19124008 | 2009 | Radial glia-like cells persist in the adult rat brain. | Gubert F et al |
| 15951811 | 2005 | Neuronal fate determinants of adult olfactory bulb neurogenesis. | Hack MA et al |
| 8664548 | 1995 | New perspectives on eye evolution. | Halder G et al |
| 15548580 | 2004 | Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development. | Haubst N et al |
| 11896398 | 2002 | Glial cells generate neurons: the role of the transcription factor Pax6. | Heins N et al |
| 18070176 | 2008 | Methylation of the TPEF- and PAX6-promoters is increased in early bladder cancer and in normal mucosa adjacent to pTa tumours. | Hellwinkel OJ et al |
| 1684639 | 1991 | Mouse small eye results from mutations in a paired-like homeobox-containing gene. | Hill RE et al |
| 19218613 | 2009 | Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations. | Hingorani M et al |
| 17158062 | 2007 | Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon. | Holm PC et al |
| 12534968 | 2003 | Subpial neuronal migration in the medulla oblongata of Pax-6-deficient rats. | Horie M et al |
| 9882499 | 1999 | Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity. | Kammandel B et al |
| 10333267 | 1999 | Pax-6 is required for thalamocortical pathway formation in fetal rats. | Kawano H et al |
| 16407227 | 2006 | Phosphorylation and transactivation of Pax6 by homeodomain-interacting protein kinase 2. | Kim EA et al |
| 10588713 | 1999 | Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development. | Kioussi C et al |
| 17014839 | 2006 | Long-range downstream enhancers are essential for Pax6 expression. | Kleinjan DA et al |
| 16049175 | 2005 | Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb. | Kohwi M et al |
| 11257223 | 2001 | EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification. | Kumar JP et al |
| 17849422 | 2008 | PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation. | Lang D et al |
| 15659382 | 2005 | Epidermal growth factor-induced proliferation requires down-regulation of Pax6 in corneal epithelial cells. | Li T et al |
| 17122106 | 2006 | Pax6 regulation in retinal cells by CCCTC binding factor. | Li T et al |
| 16164600 | 2005 | Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis. | Maekawa M et al |
| 17202185 | 2007 | Controlled overexpression of Pax6 in vivo negatively autoregulates the Pax6 locus, causing cell-autonomous defects of late cortical progenitor proliferation with little effect on cortical arealization. | Manuel M et al |
| 11301001 | 2001 | Pax6 is required for the multipotent state of retinal progenitor cells. | Marquardt T et al |
| 12962539 | 2003 | The PAX6 gene is activated by the basic helix-loop-helix transcription factor NeuroD/BETA2. | Marsich E et al |
| 19651775 | 2009 | PAX6 is expressed in pancreatic cancer and actively participates in cancer progression through activation of the MET tyrosine kinase receptor gene. | Mascarenhas JB et al |
| 9169845 | 1997 | Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain. | Mastick GS et al |
| 7981749 | 1993 | A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells. | Matsuo T et al |
| 17047041 | 2006 | PAX6 suppresses the invasiveness of glioblastoma cells and the expression of the matrix metalloproteinase-2 gene. | Mayes DA et al |
| 10051657 | 1999 | A binding site for homeodomain and Pax proteins is necessary for L1 cell adhesion molecule gene expression by Pax-6 and bone morphogenetic proteins. | Meech R et al |
| 12388550 | 2002 | PAX6, paired domain influences sequence recognition by the homeodomain. | Mishra R et al |
| 12731001 | 2003 | Polymicrogyria and absence of pineal gland due to PAX6 mutation. | Mitchell TN et al |
| 16035109 | 2005 | Expression of the transcription factor Pax 6 in the adult rat dentate gyrus. | Nacher J et al |
| 14736749 | 2004 | Misrouting of mitral cell progenitors in the Pax6/small eye rat telencephalon. | Nomura T et al |
| 9675149 | 1998 | A promoter-associated polymorphic repeat modulates PAX-6 expression in human brain. | Okladnova O et al |
| 11842182 | 2002 | Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies. | Onuma Y et al |
| 19004853 | 2008 | Dual requirement for Pax6 in retinal progenitor cells. | Oron-Karni V et al |
| 9247338 | 1997 | Pax-6 is involved in the specification of hindbrain motor neuron subtype. | Osumi N et al |
| 18467663 | 2008 | Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator. | Osumi N et al |
| 16029501 | 2005 | Regulation of the Pax6 : Pax6(5a) mRNA ratio in the developing mammalian brain. | Pinson J et al |
| 18273794 | 2007 | Mutation analysis of gene PAX6 in human gliomas. | Pinto GR et al |
| 10526314 | 1999 | Evidence that POU factor Brn-3B regulates expression of Pax-6 in neuroretina cells. | Plaza S et al |
| 10079359 | 1999 | High conservation of cis-regulatory elements between quail and human for the Pax-6 gene. | Plaza S et al |
| 12351726 | 2002 | Disruption of early events in thalamocortical tract formation in mice lacking the transcription factors Pax6 or Foxg1. | Pratt T et al |
| 11060242 | 2000 | A role for Pax6 in the normal development of dorsal thalamus and its cortical connections. | Pratt T et al |
| 9482572 | 1998 | PAX6 mutations reviewed. | Prosser J et al |
| 16979618 | 2007 | Pax6 controls cerebral cortical cell number by regulating exit from the cell cycle and specifies cortical cell identity by a cell autonomous mechanism. | Quinn JC et al |
| 8600027 | 1996 | Multiple functions for Pax6 in mouse eye and nasal development. | Quinn JC et al |
| 18241071 | 2008 | Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia. | Robinson DO et al |
| 9224716 | 1997 | Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development. | Sander M et al |
| 19521500 | 2009 | The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis. | Sansom SN et al |
| 9055817 | 1997 | Transcriptional regulation of the mouse alpha A-crystallin gene: binding of USF to the -7/+5 region. | Sax CM et al |
| 8689689 | 1996 | Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities. | Schedl A et al |
| 11707457 | 2002 | Repression of glucagon gene transcription by peroxisome proliferator-activated receptor gamma through inhibition of Pax6 transcriptional activity. | Schinner S et al |
| 8213068 | 1993 | Defects of neuronal migration and the pathogenesis of cortical malformations are associated with Small eye (Sey) in the mouse, a point mutation at the Pax-6-locus. | Schmahl W et al |
| 15229646 | 2004 | Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways. | Schuurmans C et al |
| 12386935 | 2002 | Pax6; a pleiotropic player in development. | Simpson TI et al |
| 11983873 | 2002 | Iris hypoplasia in mice that lack the alternatively spliced Pax6(5a) isoform. | Singh S et al |
| 10747901 | 2000 | Modulation of PAX6 homeodomain function by the paired domain. | Singh S et al |
| 11431688 | 2001 | PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans. | Sisodiya SM et al |
| 10885745 | 2000 | Pax-6 expression and activity are induced in the reepithelializing cornea and control activity of the transcriptional promoter for matrix metalloproteinase gelatinase B. | Sivak JM et al |
| 12370174 | 2002 | Novel target sequences for Pax-6 in the brain-specific activating regions of the rat aldolase C gene. | Skala-Rubinson H et al |
| 9163426 | 1997 | Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas. | St-Onge L et al |
| 11050125 | 2000 | Pax6 modulates the dorsoventral patterning of the mammalian telencephalon. | Stoykova A et al |
| 9828088 | 1998 | Pax6 influences the time and site of origin of glial precursors in the ventral neural tube. | Sun T et al |
| 12618140 | 2003 | Pax6 regulates regional development and neuronal migration in the cerebral cortex. | Talamillo A et al |
| 9147640 | 1997 | Functional analysis of paired box missense mutations in the PAX6 gene. | Tang HK et al |
| 10610023 | 1999 | Expression pattern of PAX3 and PAX6 genes during human embryogenesis. | Terzić J et al |
| 1684738 | 1991 | Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region. | Ton CC et al |
| 11003836 | 2000 | Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2. | Toresson H et al |
| 18307776 | 2008 | Er81 is a downstream target of Pax6 in cortical progenitors. | Tuoc TC et al |
| 12764036 | 2003 | Pax6 regulates cell adhesion during cortical development. | Tyas DA et al |
| 16674807 | 2006 | Functional conservation of Pax6 regulatory elements in humans and mice demonstrated with a novel transgenic reporter mouse. | Tyas DA et al |
| 1687460 | 1991 | Pax-6, a murine paired box gene, is expressed in the developing CNS. | Walther C et al |
| 10498281 | 1999 | The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex. | Warren N et al |
| 9108373 | 1997 | Roles of Pax-6 in murine diencephalic development. | Warren N et al |
| 9622640 | 1998 | A highly conserved lens transcriptional control element from the Pax-6 gene. | Williams SC et al |
| 16723452 | 2006 | Effect of CTCF-binding motif on regulation of PAX6 transcription. | Wu D et al |
| 9847251 | 1999 | Regulation of Pax6 expression is conserved between mice and flies. | Xu PX et al |
| 9883578 | 1998 | PAX6 intronic sequence targets expression to the spinal cord. | Xu ZP et al |
| 11688562 | 2001 | Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum. | Yamasaki T et al |
| 17374606 | 2007 | Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development. | Yan Q et al |
| 11124115 | 2001 | Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon. | Yun K et al |
| 12481295 | 2003 | Cre-loxp fate-mapping of Pax6 enhancer active retinal and pancreatic progenitors. | Zhang X et al |
| 11574690 | 2001 | Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1. | Zheng JB et al |
| 10717483 | 2000 | A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements? | Zhou Y et al |
| 19618119 | 2010 | PAX6 suppression of glioma angiogenesis and the expression of vascular endothelial growth factor A. | Zhou YH et al |
| 12960124 | 2003 | The expression of PAX6, PTEN, vascular endothelial growth factor, and epidermal growth factor receptor in gliomas: relationship to tumor grade and survival. | Zhou YH et al |
| 15735909 | 2005 | PAX6 suppresses growth of human glioblastoma cells. | Zhou YH et al |
| 12421758 | 2002 | Novel PAX6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation. | Zhou YH et al |
| 12015275 | 2002 | PAX6 in sensory development. | van Heyningen V et al |
| 11076764 | 2000 | Dosage requirement and allelic expression of PAX6 during lens placode formation. | van Raamsdonk CD et al |
Other Information
Locus ID:
NCBI: 5080
MIM: 607108
HGNC: 8620
Ensembl: ENSG00000007372
Variants:
dbSNP: 5080
ClinVar: 5080
TCGA: ENSG00000007372
COSMIC: PAX6
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 38056551 | 2024 | Reduction of lens size in PAX6-related aniridia. | 0 |
| 38441200 | 2024 | Novel and recurrent variants in PAX6 in four patients with ocular phenotypes from Southeast Asia. | 0 |
| 38679634 | 2024 | A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology. | 1 |
| 38745318 | 2024 | PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility. | 2 |
| 38056551 | 2024 | Reduction of lens size in PAX6-related aniridia. | 0 |
| 38441200 | 2024 | Novel and recurrent variants in PAX6 in four patients with ocular phenotypes from Southeast Asia. | 0 |
| 38679634 | 2024 | A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology. | 1 |
| 38745318 | 2024 | PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility. | 2 |
| 36202929 | 2023 | Whole-genome sequencing of multiple related individuals with type 2 diabetes reveals an atypical likely pathogenic mutation in the PAX6 gene. | 1 |
| 36205257 | 2023 | Differential role of Pax6 and its interaction with Shh-Gli1-IDH2 axis in regulation of glioma growth and chemoresistance. | 0 |
| 36599958 | 2023 | A new association of PAX6 variation with Juvenile onset open angle glaucoma. | 1 |
| 36675087 | 2023 | Minigene Splicing Assays and Long-Read Sequencing to Unravel Pathogenic Deep-Intronic Variants in PAX6 in Congenital Aniridia. | 0 |
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Citation
Yi-Hong Zhou
PAX6 (paired box 6)
Atlas Genet Cytogenet Oncol Haematol. 2009-08-01
Online version: http://atlasgeneticsoncology.org/gene/211/pax6-(paired-box-6)
