PAX6

This gene encodes a homeobox and paired domain-containing protein that binds DNA and functions as a regulator of transcription. Activity of this protein is key in the development of neural tissues, particularly the eye. This gene is regulated by multiple enhancers located up to hundreds of kilobases distant from this locus. Mutations in this gene or in the enhancer regions can cause ocular disorders such as aniridia and Peter's anomaly. Use of alternate promoters and alternative splicing result in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2015]

Paired Box 6

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 (By similarity).
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 (By similarity).
Acts as a transcriptional repressor of NFATC1-mediated gene expression (By similarity).

Anatomical structure developmentManual Assertion Based On ExperimentIBA:GO_Central
Animal organ morphogenesisManual Assertion Based On ExperimentTAS:ProtInc
Astrocyte differentiationIEA:Ensembl
Axon guidanceIEA:Ensembl
Blood vessel developmentManual Assertion Based On ExperimentIMP:DFLAT
Cell fate determinationIEA:Ensembl
Cellular response to leukemia inhibitory factorIEA:Ensembl
Central nervous system developmentManual Assertion Based On ExperimentTAS:ProtInc
Cerebral cortex regionalizationIEA:Ensembl
Commitment of neuronal cell to specific neuron type in forebrainIEA:Ensembl
Cornea development in camera-type eyeManual Assertion Based On ExperimentIMP:DFLAT
Dorsal/ventral axis specificationIEA:Ensembl
Embryonic camera-type eye morphogenesisIEA:Ensembl
Establishment of mitotic spindle orientationIEA:Ensembl
Eye developmentManual Assertion Based On ExperimentTAS:ProtInc
Eye photoreceptor cell developmentIEA:Ensembl
Forebrain dorsal/ventral pattern formationIEA:Ensembl
Forebrain-midbrain boundary formationIEA:Ensembl
Gene expressionIEA:Ensembl
Glucose homeostasisManual Assertion Based On ExperimentIMP:DFLAT
Habenula developmentIEA:Ensembl
Iris morphogenesisManual Assertion Based On ExperimentIMP:DFLAT
Keratinocyte differentiationIEA:Ensembl
Lacrimal gland developmentIEA:Ensembl
Lens development in camera-type eyeIEA:Ensembl
Negative regulation of epithelial cell proliferationIEA:Ensembl
Negative regulation of neural precursor cell proliferationIEA:Ensembl
Negative regulation of neurogenesisISS:UniProtKB
Negative regulation of neuron differentiationIEA:Ensembl
Negative regulation of protein phosphorylationIEA:Ensembl
Negative regulation of transcription by RNA polymerase IIISS:UniProtKB
Neuron fate commitment1 PublicationNAS:UniProtKB
Neuron migrationIEA:Ensembl
Oligodendrocyte cell fate specificationIEA:Ensembl
Pancreatic A cell developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Pituitary gland developmentIEA:Ensembl
Positive regulation of core promoter bindingManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of epithelial cell differentiationIEA:Ensembl
Positive regulation of gene expressionManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of neuroblast proliferationIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:UniProtKB
Protein localization to organelleIEA:Ensembl
Regulation of asymmetric cell divisionIEA:Ensembl
Regulation of cell migrationIEA:Ensembl
Regulation of timing of cell differentiationIEA:Ensembl
Regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIBA:GO_Central
Response to woundingManual Assertion Based On ExperimentIEP:UniProtKB
Retina development in camera-type eyeIEA:Ensembl
Salivary gland morphogenesisIEA:Ensembl
Signal transduction involved in regulation of gene expressionIEA:Ensembl
Smoothened signaling pathwayIEA:Ensembl
Type B pancreatic cell differentiationIEA:Ensembl
Ventral spinal cord developmentISS:UniProtKB
Visual perceptionManual Assertion Based On ExperimentTAS:ProtInc

Nucleus

Aniridia 1 (AN1):
A congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.
Anterior segment dysgenesis 5 (ASGD5):
A form of anterior segment dysgenesis, a group of defects affecting anterior structures of the eye including cornea, iris, lens, trabecular meshwork, and Schlemm canal. Anterior segment dysgeneses result from abnormal migration or differentiation of the neural crest derived mesenchymal cells that give rise to components of the anterior chamber during eye development. Different anterior segment anomalies may exist alone or in combination, including iris hypoplasia, enlarged or reduced corneal diameter, corneal vascularization and opacity, posterior embryotoxon, corectopia, polycoria, abnormal iridocorneal angle, ectopia lentis, and anterior synechiae between the iris and posterior corneal surface. Clinical conditions falling within the phenotypic spectrum of anterior segment dysgeneses include aniridia, Axenfeld anomaly, Reiger anomaly/syndrome, Peters anomaly, and iridogoniodysgenesis.
Foveal hypoplasia 1 (FVH1):
An isolated form of foveal hypoplasia, a developmental defect of the eye defined as the lack of foveal depression with continuity of all neurosensory retinal layers in the presumed foveal area. Clinical features include absence of foveal pit on optical coherence tomography, absence of foveal hyperpigmentation, absence of foveal avascularity, absence of foveal and macular reflexes, decreased visual acuity, and nystagmus. Anterior segment anomalies and cataract are observed in some FVH1 patients.
Keratitis hereditary (KERH):
An ocular disorder characterized by corneal opacification, recurrent stromal keratitis and vascularization.
Coloboma, ocular, autosomal dominant (COAD):
A set of malformations resulting from abnormal morphogenesis of the optic cup and stalk, and the fusion of the fetal fissure (optic fissure). The clinical presentation is variable. Some individuals may present with minimal defects in the anterior iris leaf without other ocular defects. More complex malformations create a combination of iris, uveoretinal and/or optic nerve defects without or with microphthalmia or even anophthalmia.
Coloboma of optic nerve (COLON):
An ocular defect that is due to malclosure of the fetal intraocular fissure affecting the optic nerve head. In some affected individuals, it appears as enlargement of the physiologic cup with severely affected eyes showing huge cavities at the site of the disk.
Bilateral optic nerve hypoplasia (BONH):
A congenital anomaly in which the optic disk appears abnormally small. It may be an isolated finding or part of a spectrum of anatomic and functional abnormalities that includes partial or complete agenesis of the septum pellucidum, other midline brain defects, cerebral anomalies, pituitary dysfunction, and structural abnormalities of the pituitary.
Aniridia 2 (AN2):
A form of aniridia, a congenital, bilateral, panocular disorder characterized by complete absence of the iris or extreme iris hypoplasia. Aniridia is not just an isolated defect in iris development but it is associated with macular and optic nerve hypoplasia, cataract, corneal changes, nystagmus. Visual acuity is generally low but is unrelated to the degree of iris hypoplasia. Glaucoma is a secondary problem causing additional visual loss over time.

Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal degradation.