PAX6

Developmental stage

Expressed in the developing eye and brain. Expression in the retina peaks at fetal days 51-60. At 6-week old, in the retina, is predominantly detected in the neural layer (at protein level). At 8- and 10-week old, in the retina, the expression is strongest in the inner and middle layer of the neural part (at protein level).

Function

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).

Involvement in disease

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

Keratitis hereditary

KERH

An ocular disorder characterized by corneal opacification, recurrent stromal keratitis and vascularization.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The disease is caused by variants affecting the gene represented in this entry.

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.

None

The gene represented in this entry is involved in disease pathogenesis. A mutation in a PAX6 long-range cis-regulatory element, known as SIMO, affects PAX6 expression in the developing eye and has pathological consequences. The mutation is located in ELP4 intron 9, 150 kb downstream of PAX6.

Post-translational modifications

Ubiquitinated by TRIM11, leading to ubiquitination and proteasomal degradation.

Sequence similarities

Belongs to the paired homeobox family.

Tissue specificity

Isoform 1

Expressed in lymphoblasts.

Isoform 5a

Weakly expressed in lymphoblasts.

Cellular localization

• Nucleus
• Isoform 1
• Nucleus
• Isoform 5a
• Nucleus

Alternative names

• Paired box protein Pax-6
• Aniridia type II protein
• Oculorhombin
• AN2
• PAX6

Database links

• entrezGene:5080
• omim:607108
• swissprot:P26367

Target type

Proteins

Primary research area

Neuroscience

Other research areas

• Epigenetics

Molecular weight

46683Da