PAX6 (paired box 6)

2009-08-01   Yi-Hong Zhou  

Department of Neurological Surgery, Department of Biological Chemistry (joint), University of California, Irvine, Med Sci I, Room C214, Irvine, CA 92697, USA

Identity

HGNC
PAX6
LOCATION
11p13
LOCUSID
5080
ALIAS
AN,AN1,AN2,ASGD5,D11S812E,FVH1,MGDA,WAGR
FUSION GENES
Show Gene Fusions

DNA/RNA

Atlas Image

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

Atlas Image
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).

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).

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
WAGR syndrome
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 IDLast YearTitleAuthors
145860162003R-cadherin is a Pax6-regulated, growth-promoting cue for pioneer axons.Andrews GL et al
174542332007Auditory and verbal working memory deficits in a child with congenital aniridia due to a PAX6 mutation.Bamiou DE et al
174856222007Auditory interhemispheric transfer deficits, hearing difficulties, and brain magnetic resonance imaging abnormalities in children with congenital aniridia due to PAX6 mutations.Bamiou DE et al
103193221999Tissue-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
173996982007The on/off of Pax6 controls the tempo of neuronal differentiation in the developing spinal cord.Bel-Vialar S et al
104512271999Pax6 is implicated in murine pituitary endocrine function.Bentley CA et al
173293672007Conditional activation of Pax6 in the developing cortex of transgenic mice causes progenitor apoptosis.Berger J et al
178739002007Chromosomal and methylation alterations in sporadic and familial adenomatous polyposis-related duodenal carcinomas.Berkhout M et al
107646492000Regulation of area identity in the mammalian neocortex by Emx2 and Pax6.Bishop KM et al
185626152008A dlx2- and pax6-dependent transcriptional code for periglomerular neuron specification in the adult olfactory bulb.Brill MS et al
182247152008Transcription factors CTCF and Pax6 are segregated to different cell types during retinal cell differentiation.Canto-Soler MV et al
93624661997Determination of the migratory capacity of embryonic cortical cells lacking the transcription factor Pax-6.Carić D et al
173184122007PAX6 increases glioma cell susceptibility to detachment and oxidative stress.Chang JY et al
125525612003Missense mutations in the DNA-binding region and termination codon in PAX6.Chao LY et al
124851662002A comparative cDNA microarray analysis reveals a spectrum of genes regulated by Pax6 in mouse lens.Chauhan BK et al
150375752004Corneal development, limbal stem cell function, and corneal epithelial cell migration in the Pax6(+/-) mouse.Collinson JM et al
155584752004Regulation of gene expression by Pax6 in ocular cells: a case of tissue-preferred expression of crystallins in lens.Cvekl A et al
126921532003Requirement for Pax6 in corneal morphogenesis: a role in adhesion.Davis J et al
87564381996Role of Olf-1 and Pax-6 transcription factors in neurodevelopment.Davis JA et al
183227022008Pax6 3' deletion results in aniridia, autism and mental retardation.Davis LK et al
107048872000Pax genes and the differentiation of hormone-producing endocrine cells in the pancreas.Dohrmann C et al
97106411998Dual roles for Pax-6: a transcriptional repressor of lens fiber cell-specific beta-crystallin genes.Duncan MK et al
171572872007Pax6 controls the proliferation rate of neuroepithelial progenitors from the mouse optic vesicle.Duparc RH et al
104095041999Role of Pax6 in development of the cerebellar system.Engelkamp D et al
81325581994Identification of a Pax paired domain recognition sequence and evidence for DNA-dependent conformational changes.Epstein J et al
79588751994Two independent and interactive DNA-binding subdomains of the Pax6 paired domain are regulated by alternative splicing.Epstein JA et al
92303121997Pax6 controls progenitor cell identity and neuronal fate in response to graded Shh signaling.Ericson J et al
118070372002Pax6 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
146837292003Quantitative MR image analysis in subjects with defects in the PAX6 gene.Free SL et al
156535582005New perspectives on eye development and the evolution of eyes and photoreceptors.Gehring WJ et al
13451751992Genomic structure, evolutionary conservation and aniridia mutations in the human PAX6 gene.Glaser T et al
98564591998Pax6 controls radial glia differentiation in the cerebral cortex.Götz M et al
161158812005The Optimedin gene is a downstream target of Pax6.Grinchuk O et al
92326021997Disruption 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
172511902007The MH1 domain of Smad3 interacts with Pax6 and represses autoregulation of the Pax6 P1 promoter.Grocott T et al
114797302001Population-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
191240082009Radial glia-like cells persist in the adult rat brain.Gubert F et al
159518112005Neuronal fate determinants of adult olfactory bulb neurogenesis.Hack MA et al
86645481995New perspectives on eye evolution.Halder G et al
155485802004Molecular dissection of Pax6 function: the specific roles of the paired domain and homeodomain in brain development.Haubst N et al
118963982002Glial cells generate neurons: the role of the transcription factor Pax6.Heins N et al
180701762008Methylation of the TPEF- and PAX6-promoters is increased in early bladder cancer and in normal mucosa adjacent to pTa tumours.Hellwinkel OJ et al
16846391991Mouse small eye results from mutations in a paired-like homeobox-containing gene.Hill RE et al
192186132009Detailed ophthalmologic evaluation of 43 individuals with PAX6 mutations.Hingorani M et al
171580622007Loss- and gain-of-function analyses reveal targets of Pax6 in the developing mouse telencephalon.Holm PC et al
125349682003Subpial neuronal migration in the medulla oblongata of Pax-6-deficient rats.Horie M et al
98824991999Distinct cis-essential modules direct the time-space pattern of the Pax6 gene activity.Kammandel B et al
103332671999Pax-6 is required for thalamocortical pathway formation in fetal rats.Kawano H et al
164072272006Phosphorylation and transactivation of Pax6 by homeodomain-interacting protein kinase 2.Kim EA et al
105887131999Pax6 is essential for establishing ventral-dorsal cell boundaries in pituitary gland development.Kioussi C et al
170148392006Long-range downstream enhancers are essential for Pax6 expression.Kleinjan DA et al
160491752005Pax6 is required for making specific subpopulations of granule and periglomerular neurons in the olfactory bulb.Kohwi M et al
112572232001EGF receptor and Notch signaling act upstream of Eyeless/Pax6 to control eye specification.Kumar JP et al
178494222008PAX6 is expressed in pancreatic adenocarcinoma and is downregulated during induction of terminal differentiation.Lang D et al
156593822005Epidermal growth factor-induced proliferation requires down-regulation of Pax6 in corneal epithelial cells.Li T et al
171221062006Pax6 regulation in retinal cells by CCCTC binding factor.Li T et al
161646002005Pax6 is required for production and maintenance of progenitor cells in postnatal hippocampal neurogenesis.Maekawa M et al
172021852007Controlled 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
113010012001Pax6 is required for the multipotent state of retinal progenitor cells.Marquardt T et al
129625392003The PAX6 gene is activated by the basic helix-loop-helix transcription factor NeuroD/BETA2.Marsich E et al
196517752009PAX6 is expressed in pancreatic cancer and actively participates in cancer progression through activation of the MET tyrosine kinase receptor gene.Mascarenhas JB et al
91698451997Pax-6 functions in boundary formation and axon guidance in the embryonic mouse forebrain.Mastick GS et al
79817491993A mutation in the Pax-6 gene in rat small eye is associated with impaired migration of midbrain crest cells.Matsuo T et al
170470412006PAX6 suppresses the invasiveness of glioblastoma cells and the expression of the matrix metalloproteinase-2 gene.Mayes DA et al
100516571999A 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
123885502002PAX6, paired domain influences sequence recognition by the homeodomain.Mishra R et al
127310012003Polymicrogyria and absence of pineal gland due to PAX6 mutation.Mitchell TN et al
160351092005Expression of the transcription factor Pax 6 in the adult rat dentate gyrus.Nacher J et al
147367492004Misrouting of mitral cell progenitors in the Pax6/small eye rat telencephalon.Nomura T et al
96751491998A promoter-associated polymorphic repeat modulates PAX-6 expression in human brain.Okladnova O et al
118421822002Conservation of Pax 6 function and upstream activation by Notch signaling in eye development of frogs and flies.Onuma Y et al
190048532008Dual requirement for Pax6 in retinal progenitor cells.Oron-Karni V et al
92473381997Pax-6 is involved in the specification of hindbrain motor neuron subtype.Osumi N et al
184676632008Concise review: Pax6 transcription factor contributes to both embryonic and adult neurogenesis as a multifunctional regulator.Osumi N et al
160295012005Regulation of the Pax6 : Pax6(5a) mRNA ratio in the developing mammalian brain.Pinson J et al
182737942007Mutation analysis of gene PAX6 in human gliomas.Pinto GR et al
105263141999Evidence that POU factor Brn-3B regulates expression of Pax-6 in neuroretina cells.Plaza S et al
100793591999High conservation of cis-regulatory elements between quail and human for the Pax-6 gene.Plaza S et al
123517262002Disruption of early events in thalamocortical tract formation in mice lacking the transcription factors Pax6 or Foxg1.Pratt T et al
110602422000A role for Pax6 in the normal development of dorsal thalamus and its cortical connections.Pratt T et al
94825721998PAX6 mutations reviewed.Prosser J et al
169796182007Pax6 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
86000271996Multiple functions for Pax6 in mouse eye and nasal development.Quinn JC et al
182410712008Genetic analysis of chromosome 11p13 and the PAX6 gene in a series of 125 cases referred with aniridia.Robinson DO et al
92247161997Genetic analysis reveals that PAX6 is required for normal transcription of pancreatic hormone genes and islet development.Sander M et al
195215002009The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis.Sansom SN et al
90558171997Transcriptional regulation of the mouse alpha A-crystallin gene: binding of USF to the -7/+5 region.Sax CM et al
86896891996Influence of PAX6 gene dosage on development: overexpression causes severe eye abnormalities.Schedl A et al
117074572002Repression of glucagon gene transcription by peroxisome proliferator-activated receptor gamma through inhibition of Pax6 transcriptional activity.Schinner S et al
82130681993Defects 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
152296462004Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways.Schuurmans C et al
123869352002Pax6; a pleiotropic player in development.Simpson TI et al
119838732002Iris hypoplasia in mice that lack the alternatively spliced Pax6(5a) isoform.Singh S et al
107479012000Modulation of PAX6 homeodomain function by the paired domain.Singh S et al
114316882001PAX6 haploinsufficiency causes cerebral malformation and olfactory dysfunction in humans.Sisodiya SM et al
108857452000Pax-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
123701742002Novel target sequences for Pax-6 in the brain-specific activating regions of the rat aldolase C gene.Skala-Rubinson H et al
91634261997Pax6 is required for differentiation of glucagon-producing alpha-cells in mouse pancreas.St-Onge L et al
110501252000Pax6 modulates the dorsoventral patterning of the mammalian telencephalon.Stoykova A et al
98280881998Pax6 influences the time and site of origin of glial precursors in the ventral neural tube.Sun T et al
126181402003Pax6 regulates regional development and neuronal migration in the cerebral cortex.Talamillo A et al
91476401997Functional analysis of paired box missense mutations in the PAX6 gene.Tang HK et al
106100231999Expression pattern of PAX3 and PAX6 genes during human embryogenesis.Terzić J et al
16847381991Positional cloning and characterization of a paired box- and homeobox-containing gene from the aniridia region.Ton CC et al
110038362000Genetic control of dorsal-ventral identity in the telencephalon: opposing roles for Pax6 and Gsh2.Toresson H et al
183077762008Er81 is a downstream target of Pax6 in cortical progenitors.Tuoc TC et al
127640362003Pax6 regulates cell adhesion during cortical development.Tyas DA et al
166748072006Functional conservation of Pax6 regulatory elements in humans and mice demonstrated with a novel transgenic reporter mouse.Tyas DA et al
16874601991Pax-6, a murine paired box gene, is expressed in the developing CNS.Walther C et al
104982811999The transcription factor, Pax6, is required for cell proliferation and differentiation in the developing cerebral cortex.Warren N et al
91083731997Roles of Pax-6 in murine diencephalic development.Warren N et al
96226401998A highly conserved lens transcriptional control element from the Pax-6 gene.Williams SC et al
167234522006Effect of CTCF-binding motif on regulation of PAX6 transcription.Wu D et al
98472511999Regulation of Pax6 expression is conserved between mice and flies.Xu PX et al
98835781998PAX6 intronic sequence targets expression to the spinal cord.Xu ZP et al
116885622001Pax6 regulates granule cell polarization during parallel fiber formation in the developing cerebellum.Yamasaki T et al
173746062007Protein phosphatase-1 modulates the function of Pax-6, a transcription factor controlling brain and eye development.Yan Q et al
111241152001Gsh2 and Pax6 play complementary roles in dorsoventral patterning of the mammalian telencephalon.Yun K et al
124812952003Cre-loxp fate-mapping of Pax6 enhancer active retinal and pancreatic progenitors.Zhang X et al
115746902001Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1.Zheng JB et al
107174832000A novel Pax-6 binding site in rodent B1 repetitive elements: coevolution between developmental regulation and repeated elements?Zhou Y et al
196181192010PAX6 suppression of glioma angiogenesis and the expression of vascular endothelial growth factor A.Zhou YH et al
129601242003The 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
157359092005PAX6 suppresses growth of human glioblastoma cells.Zhou YH et al
124217582002Novel PAX6 binding sites in the human genome and the role of repetitive elements in the evolution of gene regulation.Zhou YH et al
120152752002PAX6 in sensory development.van Heyningen V et al
110767642000Dosage 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

Gene IDTranscript IDUniprot
ENSG00000007372ENST00000241001P26367
ENSG00000007372ENST00000241001Q66SS1
ENSG00000007372ENST00000379107P26367
ENSG00000007372ENST00000379107F1T0F8
ENSG00000007372ENST00000379109P26367
ENSG00000007372ENST00000379109Q66SS1
ENSG00000007372ENST00000379111A0A1W2PQA8
ENSG00000007372ENST00000379115A0A1X7SBT0
ENSG00000007372ENST00000379123A0A1W2PPJ2
ENSG00000007372ENST00000379129P26367
ENSG00000007372ENST00000379129F1T0F8
ENSG00000007372ENST00000379132P26367
ENSG00000007372ENST00000379132Q66SS1
ENSG00000007372ENST00000419022P26367
ENSG00000007372ENST00000419022F1T0F8
ENSG00000007372ENST00000423822B1B1I9
ENSG00000007372ENST00000438681B1B1I8
ENSG00000007372ENST00000455099B1B1J0
ENSG00000007372ENST00000481563A0A1W2PRA8
ENSG00000007372ENST00000524853E9PKM0
ENSG00000007372ENST00000606377P26367
ENSG00000007372ENST00000606377F1T0F8
ENSG00000007372ENST00000638250A0A1W2PPJ2
ENSG00000007372ENST00000638346A0A1W2PP27
ENSG00000007372ENST00000638629A0A1W2PRA8
ENSG00000007372ENST00000638685A0A1W2PRH6
ENSG00000007372ENST00000638696A0A1W2PS91
ENSG00000007372ENST00000638755A0A1W2PQM7
ENSG00000007372ENST00000638762A0A1W2PPG3
ENSG00000007372ENST00000638802A0A1W2PRU4
ENSG00000007372ENST00000638853A0A1W2PQ31
ENSG00000007372ENST00000638878A0A1W2PQG3
ENSG00000007372ENST00000638914P26367
ENSG00000007372ENST00000638914F1T0F8
ENSG00000007372ENST00000638963A0A1W2PQG7
ENSG00000007372ENST00000638965A0A1W2PSB5
ENSG00000007372ENST00000639006A0A1W2PP89
ENSG00000007372ENST00000639034D1KF47
ENSG00000007372ENST00000639061A0A1W2PPH0
ENSG00000007372ENST00000639079A0A1W2PQJ8
ENSG00000007372ENST00000639109A0A1W2PQ31
ENSG00000007372ENST00000639386A0A1W2PRA8
ENSG00000007372ENST00000639394A0A1W2PQW3
ENSG00000007372ENST00000639409P26367
ENSG00000007372ENST00000639409F1T0F8
ENSG00000007372ENST00000639548A0A1W2PRA8
ENSG00000007372ENST00000639916P26367
ENSG00000007372ENST00000639916Q66SS1
ENSG00000007372ENST00000639920A0A1W2PR58
ENSG00000007372ENST00000639943A0A1W2PPM5
ENSG00000007372ENST00000639950A0A1W2PQA8
ENSG00000007372ENST00000640125A0A1W2PRA8
ENSG00000007372ENST00000640242A0A1W2PRS6
ENSG00000007372ENST00000640287P26367
ENSG00000007372ENST00000640287Q66SS1
ENSG00000007372ENST00000640335A0A1W2PRW7
ENSG00000007372ENST00000640368P26367
ENSG00000007372ENST00000640368F1T0F8
ENSG00000007372ENST00000640431A0A1W2PQL7
ENSG00000007372ENST00000640460A0A1W2PSA8
ENSG00000007372ENST00000640610P26367
ENSG00000007372ENST00000640610Q66SS1
ENSG00000007372ENST00000640613A0A1W2PRG3
ENSG00000007372ENST00000640684A0A1W2PPN2
ENSG00000007372ENST00000640766A0A1W2PPH0
ENSG00000007372ENST00000640872A0A1W2PNS7
ENSG00000007372ENST00000640963A0A1W2PRA4
ENSG00000007372ENST00000640975P26367
ENSG00000007372ENST00000640975F1T0F8
ENSG00000007372ENST00000643871P26367
ENSG00000007372ENST00000643871Q66SS1

Expression (GTEx)

0
5
10
15
20
25
30
35
40
45
Adipose - Subcutaneous
Adipose - Visceral
Adrenal Gland
Artery - Aorta
Artery - Tibial
Bladder
Brain - Amygdala
Brain - Anterior cingulate cortex
Brain - Caudate
Brain - Cerebellar Hemisphere
Brain - Cerebellum
Brain - Cortex
Brain - Frontal Cortex
Brain - Hippocampus
Brain - Hypothalamus
Brain - Nucleus accumbens
Brain - Putamen
Brain - Spinal cord
Brain - Substantia nigra
Breast - Mammary Tissue
Cells - Cultured fibroblasts
Cells - EBV - transformed lymphocytes
Cervix - Ectocervix
Cervix - Endocervix
Colon - Sigmoid
Colon - Transverse
Esophagus - Gastroesophageal Junction
Esophagus - Mucosa
Esophagus - Muscularis
Fallopian Tube
Heart - Atrial Appendage
Heart - Left Ventricle
Kidney - Cortex
Kidney - Medulla
Liver
Lung
Minor Salivary Gland
Muscle - Skeletal
Nerve - Tibial
Ovary
Pancreas
Pituitary
Prostate
Skin - Not Sun Exposed
Skin - Sun Exposed
Small Intestine - Terminal Ileum
Spleen
Stomach
Testis
Thyroid
Uterus
Vagina
Whole Blood

Pathways

PathwaySourceExternal ID
Maturity onset diabetes of the youngKEGGko04950
Maturity onset diabetes of the youngKEGGhsa04950
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Metabolism of proteinsREACTOMER-HSA-392499
Peptide hormone metabolismREACTOMER-HSA-2980736
Incretin synthesis, secretion, and inactivationREACTOMER-HSA-400508
Synthesis, secretion, and inactivation of Glucagon-like Peptide-1 (GLP-1)REACTOMER-HSA-381771
Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)REACTOMER-HSA-400511
Developmental BiologyREACTOMER-HSA-1266738
Regulation of beta-cell developmentREACTOMER-HSA-186712
Regulation of gene expression in beta cellsREACTOMER-HSA-210745
Activation of HOX genes during differentiationREACTOMER-HSA-5619507
Activation of anterior HOX genes in hindbrain development during early embryogenesisREACTOMER-HSA-5617472

Protein levels (Protein atlas)

Not detected
Low
Medium
High
cerebral cortex
cerebellum
hippocampus
caudate
retina
thyroid gland
parathyroid gland
adrenal gland
nasopharynx
bronchus
lung
oral mucosa
salivary gland
esophagus
stomach 1
stomach 2
duodenum
small intestine
colon
rectum
liver
gallbladder
pancreas
kidney
urinary bladder
testis
epididymis
seminal vesicle
prostate
vagina
ovary
fallopian tube
endometrium 1
endometrium 2
cervix, uterine
placenta
breast
heart muscle
smooth muscle
skeletal muscle
soft tissue 1
soft tissue 2
adipose tissue
skin 1
skin 2
appendix
spleen
lymph node
tonsil
bone marrow

References

Pubmed IDYearTitleCitations
380565512024Reduction of lens size in PAX6-related aniridia.0
384412002024Novel and recurrent variants in PAX6 in four patients with ocular phenotypes from Southeast Asia.0
386796342024A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology.1
387453182024PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.2
380565512024Reduction of lens size in PAX6-related aniridia.0
384412002024Novel and recurrent variants in PAX6 in four patients with ocular phenotypes from Southeast Asia.0
386796342024A positive feedback inhibition of isocitrate dehydrogenase 3β on paired-box gene 6 promotes Alzheimer-like pathology.1
387453182024PAX6 promotes neuroendocrine phenotypes of prostate cancer via enhancing MET/STAT5A-mediated chromatin accessibility.2
362029292023Whole-genome sequencing of multiple related individuals with type 2 diabetes reveals an atypical likely pathogenic mutation in the PAX6 gene.1
362052572023Differential role of Pax6 and its interaction with Shh-Gli1-IDH2 axis in regulation of glioma growth and chemoresistance.0
365999582023A new association of PAX6 variation with Juvenile onset open angle glaucoma.1
366750872023Minigene Splicing Assays and Long-Read Sequencing to Unravel Pathogenic Deep-Intronic Variants in PAX6 in Congenital Aniridia.0
367667422023PAX6 Expression Patterns in the Adult Human Limbal Stem Cell Niche.4
371911192023Novel variants in the PAX6 gene related to isolated aniridia.1
372669522023Association of Polymorphisms in ZFHX1B and PAX6 With Anisometropia in Chinese Children: The Hong Kong Children Eye Genetics Study.1

Citation

Yi-Hong Zhou

PAX6 (paired box 6)

Atlas Genet Cytogenet Oncol Haematol. 2009-08-01

Online version: http://atlasgeneticsoncology.org/gene/211/case-report-explorer/img/css/template-nav.css