Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
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
    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
    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
    Type ubiquitous
       expressed in (based on citations)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly
    Nervousbrainforebrain  highly Mus musculus
    Visualeye   highly
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    SystemCellPubmedSpeciesStageRna symbol
    Nervousglia Homo sapiens
    cell lineage
    cell lines
    at STAGE
    physiological period embryo, fetal
    Text developing brain, eye, nose, spinal cord
  • 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
    interspecies ortholog to Pax6, Rattus norvegicus
    ortholog to Pax6, Mus musculus
    ortholog to PAX6, Pan troglodytes
  • paired family of homeobox proteins
  • CATEGORY DNA associated , transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    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
    text eye, nose, central nervous system
    signaling sensory transduction/vision
    a component
  • proximal G1 promoter element (
  • RNA
    small molecule
  • 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
  • central role of the WNT7A-PAX6 axis in corneal epithelial cell fate determination
  • PAX6 directly regulates the activity of the ODF2 gene encoding for the appendage-specific protein ODF2 with a role for the assembly of mother centriole
  • 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
    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
    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      
    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
    constitutional       loss of function
    induces limbal stem or progenitor cells (LSCs) into skin-like epithelium, a critical defect tightly linked to common human corneal diseases
    constitutional germinal mutation      
    in microphthalmia
    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
  • 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 (