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FLASH GENE
Symbol PAX6 contributors: mct/shn - updated : 02-06-2017
HGNC name paired box 6
HGNC id 8620
Corresponding disease
AN aniridia
ASMD3 ocular anterior segment mesenchymal dysgenesis 3
ECTP ectopia pupillae
FVH foveal hypoplasia and presenile cataract syndrome
GLSPS Gillespie syndrome
KRTT keratitis hereditary
OPNAB optic nerve hypoplasia, bilateral, and coloboma
WAGR WAGR complex
Location 11p13      Physical location : 31.806.340 - 31.839.509
Synonym name
  • paired box gene 6 (aniridia, keratitis)
  • paired box protein Pax-6
  • oculorhombin
  • aniridia type II protein
  • aniridia, keratitis
  • paired box homeotic gene-6
  • Synonym symbol(s) AN2, MGDA, D11S812E, MGC17209, AN, WAGR
    DNA
    TYPE functioning gene
    STRUCTURE 26.54 kb     14 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   enhancer
    motif repetitive sequence   ALU
    text structure
  • 3' regulatory elements required for initiation of transcription (6 enhancers)
  • binding sites for Tsp2a and Tsp11b and Alu-type binding sites
  • E boxes in the promoter localized in a 1.1 kb sequence within the 4.6 kb untranslated region upstream of exon 0
  • a SIMO enhancer, crucial for expression of PAX6 in developing ocular tissues
  • MAPPING cloned Y linked N status confirmed
    Map pter - D11S914 - D11S1322 - PAX6 - D11S2370 - D11S4101 - cen
    Physical map
    KCNA4 11p14.1 potassium voltage-gated channel, shaker-related subfamily, member 4 FSHB 11p13 follicle stimulating hormone, beta polypeptide FLJ38968 11p14.1 hypothetical protein FLJ38968 C11orf8 11p13 chromosome 11 open reading frame 8 LOC387759 11 LOC387759 FLJ46154 11p14.1 FLJ46154 protein LOC341019 HCP25 11p13 cytochrome c, somatic pseudogene LOC120526 11p14.1 hypothetical protein LOC120526 FLJ25059 11p14.1 hypothetical protein FLJ25059 ELP4 11p13 elongation protein 4 homolog (S. cerevisiae) PAX6 11p13 paired box gene 6 (aniridia, keratitis) RCN1 11p13 reticulocalbin 1, EF-hand calcium binding domain LOC390105 11 similar to RIKEN cDNA 0610012H03 WT1 11p13 Wilms tumor 1 WIT-1 11p13 Wilms tumor associated protein LOC387760 11 LOC387760 GA17 11p13 LOC387760 RPL34P2 11p13 ribosomal protein L34 pseudogene 2 TMG4 11p13 transmembrane gamma-carboxyglutamic acid protein 4 FLJ21924 11p13 hypothetical protein FLJ21924 LOC91614 11p13 novel 58.3 KDA protein FLJ11336 11p13 hypothetical protein FLJ11336 PIGCP1 11p13-p12 phosphatidylinositol glycan, class C, pseudogene 1 CSTF3 11p13 cleavage stimulation factor, 3' pre-RNA, subunit 3, 77kDa LOC390107 11 similar to ribosomal protein S24 HIPK3 11p13 homeodomain interacting protein kinase 3 G2 11p13 G2 protein MGC34830 11p13 hypothetical protein MGC34830 CD59 11p13 CD59 antigen p18-20 (antigen identified by monoclonal antibodies 16.3A5, EJ16, EJ30, EL32 and G344) FBXO3 11p12 F-box only protein 3 LOC390108 11 similar to hypothetical protein MGC40611 LMO2 11p13 LIM domain only 2 (rhombotin-like 1) M11S1 11p13 membrane component, chromosome 11, surface marker 1 FLJ10774 11p13 N-acetyltransferase-like protein ABTB2 11p13 ankyrin repeat and BTB (POZ) domain containing 2
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 splicing 6947 46.6 422 nucleus 2010 19917615
  • variant p46
  • containing exon 1b, longer than 1a and overlapping the 3'-end of exon 1a
  • lacking exon 6
  • containing an altered paired box binding domain
  • both p32 and p46 displayed significant amounts of transcriptional activity on the alphaB-crystallin gene promoter
  • 14 splicing 6891 48.1 436 especially in the retinal portion where visual cells accumulate during eye development, lens, iris 2010 19917615
  • variant p48
  • containing exon 1a, shorter than 1b and overlapping the 5'-end of exon 1b
  • encodig for the longest product
  • induces a developmental cascade in the prospective fovea, area centralis or visual streak region that leads to the formation of a retinal architecture bearing densely packed visual cells
  • 12 - 6883 46.7 422 . in four ocular cell lines, and in the lens epithelium . nucleus 2010 21084637
  • both p32 and p46 displayed significant amounts of transcriptional activity on the alphaB-crystallin gene promoter
  • 11 - 1339 44.3 401 . in four ocular cell lines . in cytoplasm and nucleus 2010 19917615
  • also called PAX6S, p43
  • retains the paired domain, linker, and homeodomain of PAX6, but its C terminus is composed of a truncated classic proline, serine, and threonine domain and a unique S tail
  • noncanonical role during development
  • 8 - - 31.8 286 in four ocular cell lines 2010 21084637
  • contains only the homeodomain for DNA binding
  • sumoylation at K91 is required for p32 PAX6 to bind to a HD-specific site and regulate expression of target genes
  • sumoylation activates p32 PAX6 in both DNA-binding and transcriptional activities
  • p32 PAX6 is converted to p43 PAX6 through sumoylation
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Nervousbrainforebrain  highly Mus musculus
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousglia Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo, fetal
    Text developing brain, eye, nose, spinal cord
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a paired DNA binding domain
  • two helix-turn-helix(HTH) motif
  • an homeo domain, composed of two distinct subdomains NTS and CTS from N to C terminus
  • a glycine-rich linker domain
  • a helix turn helix (homeo) DNA binding domain
  • C terminal proline/serine/threonine transactivation domain transcribed as four alternatively spliced forms, p48, p46, p43, p32/33, from two promoters P0, P1
  • HOMOLOGY
    interspecies ortholog to Pax6, Rattus norvegicus
    ortholog to Pax6, Mus musculus
    ortholog to PAX6, Pan troglodytes
    Homologene
    FAMILY
  • paired family of homeobox proteins
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus
    basic FUNCTION
  • key (major) regulator of eye, pancreas, central nervous system development and regulator of glial precursors in the ventral neural tube
  • inducing a developemental cascade leading to the formation of a retinal architecture bearing densely packed cells
  • influences cellular proliferation, neuronal migration and axonal guidance in the brain
  • involved in the fronto-striato-thalamic functions
  • regulator of cell proliferation and lens fiber differentiation during lens regeneration
  • PAX6-dependent SHROOM3 expression regulates apical constriction during lens placode invagination (
  • crucial for endocrine cell development and function and plays an essential role in glucose homeostasis
  • controls the mRNA levels of key genes in adult pancreatic alpha cells particularly involved in glucagon gene transcription (MAFB, MAF, and NEUROD1) or glucagon biosynthesis (PCSK2) in addition to its direct control on the glucagon gene
  • acts directly on one single site of the gene promoters of MAFB and MAF, and two of NeuroD1 to control their activities in glucagon-producing cells
  • controls transcriptional expression of genes encoding both transcription factors responsible for lens development, such as musculoaponeurotic fibrosarcoma, and also lens structural proteins
  • in pallial-subpallial boundary progenitors, plays an important role in the generation of multiple subtypes of neurons that contribute to the amygdala and olfactory bulb
  • involved in the development of retinoblastoma
  • plays a crucial role in early pigment epithelium development
  • in conjunction with MITF/TFEC, PAX6 acts as an anti-retinogenic factor, whereas in conjunction with retinogenic genes it acts as a pro-retinogenic factor
  • functions as a mediator of caudal thalamus (cTh) competence
  • is likely to promote caudal thalamus (cTh) and counteract rostral thalamus (rTh) formation at the level of the signal-receiving cells
  • central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination
  • PAX6 or SIX3 is sufficient to induce ES cells to adopt a lens fate, potentially via non-cell autonomous mechanisms
  • PAX6 is a fundamental regulator of where the hem can form, and therefore implicate this molecule as a determinant of hippocampal positioning
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS development
    text eye, nose, central nervous system
    PATHWAY
    metabolism
    signaling sensory transduction/vision
    a component
    INTERACTION
    DNA
  • proximal G1 promoter element (
  • RNA
    small molecule
    protein
  • ATA-box-binding protein and retinoblastoma protein (
  • N-terminal C/H1 domain of p300 (
  • Chx10, Six3, Lhx2, En-1, Prep1, Prox1, and HoxB1 (
  • Rho GTPase effector protein, mDia (
  • LE9 (
  • PAX2
  • Karyopherin 13, Kap13 (
  • post-synaptic density (PSD) protein HOMER3, the dynein subunit DNCL1, and the tripartite motif protein TRIM11 (
  • genetic interplay between the transcription factors, PAX6 and ETV1, is responsible, in part, for the regional specification of a distinct sublineage of layer 5 projection neurons
  • autoregulatory feedback loop between TRIM11 and PAX6 maintains a balance between the levels of PAXx6 and TRIM11 proteins in cortical progenitors, having an essential role for the PAX6-dependent neurogenesis
  • MAFB, MAF, and NEUROD1 genes in pancreatic alpha cells
  • FABP7 promoter activity is upregulated by PAX6
  • KAT5 binds with PAX6 and this physical interaction leads to the full-transcriptional activation of PAX6 during retina development
  • in conjunction with MITF/TFEC, PAX6 acts as an anti-retinogenic factor, whereas in conjunction with retinogenic genes it acts as a pro-retinogenic factor
  • PCSK1N is a novel down-regulated target of PAX6 in the regulation of glucose metabolism
  • thalamus induction and patterning depends both on a prepattern of IRX3 and PAX6 expression that establishes differential cellular competence and on SHH signaling from the zona limitans intrathalamica (ZLI)organizer
  • PAX6 directly bound to and activated the prohormone convertase 1/3 (PCSK1, PCSK2, FURIN) gene promoter and subsequently regulated proinsulin processing
  • PDX1 activates downstream transcription factors NEUROG3 and PAX6, and may be one of the mechanisms that promote differentiation of induced pluripotent stem cells (iPSCs) into islet beta cells
  • overexpression of PAX6 can substitute for LHX2 in the regulation of the neuronal versus glial cell fate in the developing hippocampus
  • cell & other
    REGULATION
    activated by NEUROD1, through E boxes in the promoter
    Other regulated by CTCF in Rb cells
    dephosphorylation by protein phosphatase-1, attenuating its transcriptional activity in lens epithelial cells, dephosphorylation of TP53, attenuates its transcriptional activity and also its proapoptotic activity in both lens and nonlens cells
    ASSOCIATED DISORDERS
    corresponding disease(s) AN , ASMD3 , ECTP , FVH , OPNAB , WAGR , KRTT , GLSPS
    related resource PAX6 Mutation Database - Aniridia Type II
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    causes hypoplasia of the anterior commissure and reduced olfaction
    constitutional       loss of function
    leading to absence of the anterior commissure without callosal agenesis and absence of pineal gland, disruption of axonal guidance
    constitutional germinal mutation      
    polymicrogyria
    constitutional     --low  
    gastric expression is down-regulated in H. pylori infection and incisural antralisation
    constitutional     --over  
    causes defects of retinal axons, preventing their normal growth and navigation through the optic chiasm
    Susceptibility to extreme myopia
    Variant & Polymorphism
    Candidate gene
  • for polymicrogyria
  • haploinsufficiencies of PAX6 is a candidate gene for severe developmental delay and autistic features characteristic of WAGR syndrome
  • Marker
    Therapy target
    ANIMAL & CELL MODELS
  • Pax6(+/-) mice display corneal abnormalities (
  • overexpression of Pax6DeltaPD causes a severe microphthalmic phenotype in both wild-type and Pax6-deficient (Sey(/+)) mice in a dosage-dependent manner (
  • homozygous mutant mice for Pax6 are characterized by markedly decreased pancreatic beta and delta cells and absent alpha cells
  • Silencing the Pax6 gene with short interfering RNA resulted in an inhibited growth and an increased apoptosis of cultured human retinoblastoma cells (