Disease	Score

Substances	Interaction	Organism	Category

Substances	Interaction	Organism	Category

     aniridia More than 280 mutations in the PAX6 gene have been found to cause aniridia, which is an absence of the colored part of the eye (the iris). Most of these mutations create a premature stop signal in the instructions for making the PAX6 protein and lead to the production of an abnormally short, nonfunctional protein. As a result, there is less PAX6 protein to regulate the activity of other genes. The majority of mutations that cause aniridia occur within the PAX6 gene; however, some disease-causing mutations occur in neighboring regions of DNA that normally regulate the expression of the PAX6 gene, known as regulatory regions. Mutations in PAX6 gene regulatory regions reduce the expression of the PAX6 gene. These mutations lead to a shortage of functional PAX6 protein, which disrupts the formation of the eyes during development. coloboma Genetics Home Reference provides information about coloboma. Gillespie syndrome At least two mutations in the PAX6 gene have been identified in people with Gillespie syndrome, a disorder characterized by eye abnormalities including absence of part of the iris (partial aniridia), difficulty coordinating movements (ataxia), and mild to moderate intellectual disability. The mutations that cause Gillespie syndrome result in the absence of the PAX6 protein or production of a nonfunctional PAX6 protein that is unable to bind to DNA and regulate the activity of other genes. This lack of functional protein disrupts embryonic development, especially the development of the eyes and brain, leading to the signs and symptoms of Gillespie syndrome. microphthalmia Genetics Home Reference provides information about microphthalmia. Peters anomaly At least two mutations in the PAX6 gene have been found to cause Peters anomaly. This condition is characterized by the abnormal development of certain structures at the front of the eye and clouding of the clear front surface of the eye (cornea). The mutations that cause Peters anomaly change single protein building blocks (amino acids) in the PAX6 protein. These mutations reduce but do not eliminate the protein's function and are less severe than mutations that cause aniridia (described above). The mutations that cause Peters anomaly reduce the PAX6 protein's ability to bind to DNA, disrupting its role as a transcription factor. As a result, normal development of the eye is impaired, leading to the features of Peters anomaly. The PAX6 gene mutations that cause Peters anomaly can cause other related eye disorders in members of the same family. WAGR syndrome The PAX6 gene is located in a region of chromosome 11 that is deleted in people with WAGR syndrome, which is a disorder that affects many body systems and is named for its main features: a childhood kidney cancer known as Wilms tumor, an eye problem called anirida, genitourinary anomalies, and intellectual disability (formerly referred to as mental retardation). As a result of this deletion, affected individuals are missing one copy of the PAX6 gene in each cell. A loss of the PAX6 gene is associated with the characteristic eye features of WAGR syndrome, including aniridia, and may affect brain development. other disorders Mutations in the PAX6 gene can cause eye problems other than aniridia and Peters anomaly. The mutations that cause these eye problems occur in one copy of the PAX6 gene in each cell. Most of these mutations change single amino acids in the PAX6 protein. These mutations reduce but do not eliminate the protein's normal function, impairing its role as a transcription factor. Individuals with these relatively mild PAX6 gene mutations may be born with pupils that are not centrally positioned in the eye (ectopia papillae), small eyes (microphthalmia), and underdeveloped optic nerves, structures that carry information from the eyes to the brain. Mild PAX6 mutations can also result in a gap or split in structures that make up the eye (coloboma) or an underdeveloped region at the back of the eye responsible for sharp central vision (the fovea). Additional conditions caused by these PAX6 gene mutations may be present at birth or develop later. These conditions may include a clouding of the lens of the eye (cataracts), involuntary eye movements (nystagmus), and inflammation of the front surface of the eye called the cornea (keratitis). It is unclear why the effects of some mutations in the PAX6 gene are limited to the eye, while other mutations affect the development of many parts of the body.

     The PAX6 gene belongs to a family of genes that play a critical role in the formation of tissues and organs during embryonic development. The members of the PAX gene family are also important for maintaining the normal function of certain cells after birth. To carry out these roles, the PAX genes provide instructions for making proteins that attach to specific areas of DNA and help control the activity (expression) of particular genes. On the basis of this action, PAX proteins are called transcription factors. During embryonic development, the PAX6 protein is thought to turn on (activate) genes involved in the formation of the eyes, the brain and spinal cord (central nervous system), and the pancreas. Within the brain, the PAX6 protein is involved in the development of a specialized group of brain cells that process smell (the olfactory bulb). Additionally, researchers believe that the PAX6 protein controls many aspects of eye development before birth. After birth, the PAX6 protein likely regulates the expression of various genes in many structures of the eyes.

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

Condition	Change (log2fold)	Comparison	Species	Experimental variables	Experiment name

The following transcription factors affect gene expression:

• Pax-6
• Meis-1
• Meis-1b
• PPAR-gamma1
• PPAR-gamma2
• Pax-5
• RORalpha1

Tissue specificity:

Fetal eye, brain, spinal cord and olfactory epithelium. Isoform 5a is less abundant than the PAX6 shorter form.

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).

Molecular Function:

• Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Dna Binding
• Rna Polymerase Ii Core Promoter Sequence-Specific Dna Binding
• Rna Polymerase Ii Transcription Factor Activity, Sequence-Specific Dna Binding
• Transcriptional Activator Activity, Rna Polymerase Ii Core Promoter Proximal Region Sequence-Specific Binding
• Transcriptional Repressor Activity, Rna Polymerase Ii Transcription Regulatory Region Sequence-Specific Binding
• Dna Binding
• Chromatin Binding
• Transcription Factor Activity, Sequence-Specific Dna Binding
• Ubiquitin-Protein Transferase Activity
• Transcription Factor Binding
• Protein Kinase Binding
• Histone Acetyltransferase Binding
• R-Smad Binding

Biological Processes:

• Establishment Of Mitotic Spindle Orientation
• Blood Vessel Development
• Eye Development
• Cell Fate Determination
• Neuron Migration
• Negative Regulation Of Protein Phosphorylation
• Positive Regulation Of Neuroblast Proliferation
• Lens Development In Camera-Type Eye
• Type B Pancreatic Cell Differentiation
• Pancreatic A Cell Development
• Transcription From Rna Polymerase Ii Promoter
• Smoothened Signaling Pathway
• Axon Guidance
• Central Nervous System Development
• Salivary Gland Morphogenesis
• Visual Perception
• Response To Wounding
• Regulation Of Asymmetric Cell Division
• Animal Organ Morphogenesis
• Dorsal/Ventral Axis Specification
• Positive Regulation Of Gene Expression
• Oligodendrocyte Cell Fate Specification
• Cerebral Cortex Regionalization
• Forebrain Anterior/Posterior Pattern Specification
• Forebrain Dorsal/Ventral Pattern Formation
• Commitment Of Neuronal Cell To Specific Neuron Type In Forebrain
• Forebrain-Midbrain Boundary Formation
• Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Spinal Cord Motor Neuron Fate Specification
• Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Ventral Spinal Cord Interneuron Specification
• Regulation Of Transcription From Rna Polymerase Ii Promoter Involved In Somatic Motor Neuron Fate Commitment
• Pituitary Gland Development
• Habenula Development
• Signal Transduction Involved In Regulation Of Gene Expression
• Keratinocyte Differentiation
• Regulation Of Cell Migration
• Positive Regulation Of Epithelial Cell Differentiation
• Lacrimal Gland Development
• Protein Localization To Organelle
• Eye Photoreceptor Cell Development
• Glucose Homeostasis
• Negative Regulation Of Neuron Differentiation
• Positive Regulation Of Transcription, Dna-Templated
• Positive Regulation Of Transcription From Rna Polymerase Ii Promoter
• Regulation Of Timing Of Cell Differentiation
• Embryonic Camera-Type Eye Morphogenesis
• Neuron Fate Commitment
• Astrocyte Differentiation
• Negative Regulation Of Epithelial Cell Proliferation
• Negative Regulation Of Neurogenesis
• Retina Development In Camera-Type Eye
• Iris Morphogenesis
• Cornea Development In Camera-Type Eye
• Negative Regulation Of Neural Precursor Cell Proliferation

*synonyms