HomeAboutRankingsData Sources
Β© 2026 GeneE
🧬
GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
PAX6
paired box 6
Chromosome 11 Β· 11p13
NCBI Gene: 5080Ensembl: ENSG00000007372.25HGNC: HGNC:8620UniProt: A0A1W2PQG7
420PubMed Papers
28Diseases
0Drugs
434Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneTranscription Factor
RESEARCH IMPACT
Highly StudiedVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
chromatinblood vessel developmentcytoplasmRNA polymerase II cis-regulatory region sequence-specific DNA bindingPeters anomalyisolated aniridiaaniridiafoveal hypoplasia 1
✦AI Summary

PAX6 is a master transcription factor critical for development of the eye, central nervous system, and pancreas 1. In the cornea, PAX6 works with p63 to specify limbal stem/progenitor cells and cooperates with WNT7A to direct their differentiation into corneal epithelial cells 2. Downstream of PAX6, the transcription factor controls expression of WNK2, which maintains corneal epithelial cell-specific markers and homeostasis 3. PAX6 also regulates genes involved in retinoic acid signaling, including FABP5 and DSG1, which are essential for proper limbal epithelial differentiation 4. Beyond the eye, PAX6 acts as an inhibitory transcription factor of IDH3Ξ² in the brain; dysregulation of this axis promotes Alzheimer's-like pathology through impaired energy metabolism and tau hyperphosphorylation 5. Loss-of-function mutations in PAX6 cause aniridia and related ocular diseases including anterior segment dysgenesis, keratitis, and foveal hypoplasia 6. PAX6 haploinsufficiency leads to corneal surface disease through failure to maintain proper epithelial differentiation, a major cause of blindness worldwide 2. Notably, PAX6 transduction can reprogram skin epithelial cells to corneal fate, suggesting therapeutic potential for corneal surface disorders 2.

Sources cited
1
PAX6 is a developmental control gene encoding a transcription factor with a DNA-binding paired domain; mutations cause loss-of-function developmental defects
PMID: 7919921
2
PAX6 acts with p63 to specify limbal stem cells and with WNT7A to control corneal epithelial differentiation; PAX6 loss causes keratinization and corneal disease
PMID: 25030175
3
WNK2 is a downstream target of PAX6 essential for corneal epithelial cell differentiation and homeostasis; WNK2 knockdown impairs CEC markers and causes keratinization
PMID: 39453672
4
PAX6 regulates FABP5 and DSG1 expression in limbal epithelial cells; PAX6 knockdown decreases these differentiation markers and retinoic acid signaling components
PMID: 34954205
5
PAX6 acts as an inhibitory transcription factor of IDH3Ξ²; elevated PAX6 promotes tau hyperphosphorylation and Alzheimer's-like pathology through impaired brain glucose metabolism
PMID: 38679634
6
PAX6 mutations on chromosome 11p13 cause aniridia, Peter's anomaly, congenital cataracts, keratitis, and foveal hypoplasia; most mutations result in loss of function
PMID: 9482572
Disease Associationsβ“˜28
Peters anomalyOpen Targets
0.80Strong
isolated aniridiaOpen Targets
0.80Strong
aniridiaOpen Targets
0.77Strong
foveal hypoplasia 1Open Targets
0.77Strong
isolated optic nerve hypoplasiaOpen Targets
0.76Strong
autosomal dominant keratitisOpen Targets
0.75Strong
coloboma of optic nerveOpen Targets
0.75Strong
coloboma, ocular, autosomal dominantOpen Targets
0.72Strong
Foveal hypoplasia - presenile cataractOpen Targets
0.66Moderate
aniridia-cerebellar ataxia-intellectual disability syndromeOpen Targets
0.66Moderate
Aniridia - cerebellar ataxia - intellectual disabilityOpen Targets
0.64Moderate
colobomaOpen Targets
0.62Moderate
Familial ocular anterior segment mesenchymal dysgenesisOpen Targets
0.58Moderate
keratitisOpen Targets
0.53Moderate
Autosomal dominant optic atrophy, classic typeOpen Targets
0.53Moderate
morning glory syndromeOpen Targets
0.52Moderate
genetic disorderOpen Targets
0.51Moderate
AnophthalmiaOpen Targets
0.51Moderate
WAGR syndromeOpen Targets
0.50Moderate
early-onset non-syndromic cataractOpen Targets
0.47Moderate
Aniridia 1UniProt
Aniridia 2UniProt
Anterior segment dysgenesis 5UniProt
Bilateral optic nerve hypoplasiaUniProt
Coloboma of optic nerveUniProt
Foveal hypoplasia 1UniProt
Keratitis hereditaryUniProt
Microphthalmia/coloboma 12UniProt
Pathogenic Variants434
NM_001368894.2(PAX6):c.817dup (p.Ser273fs)Pathogenic
Aniridia 1;Irido-corneo-trabecular dysgenesis|Aniridia 1|Sporadic aniridia
β˜…β˜…β˜†β˜†2026β†’ Residue 273
NM_001368894.2(PAX6):c.120C>A (p.Cys40Ter)Pathogenic
Aniridia 1;Irido-corneo-trabecular dysgenesis|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 40
NM_001368894.2(PAX6):c.355A>T (p.Arg119Ter)Pathogenic
Aniridia 1|Aniridia 1;Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 119
NM_001368894.2(PAX6):c.241A>T (p.Arg81Ter)Pathogenic
not provided|Aniridia 1;Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 81
NM_001368894.2(PAX6):c.991C>T (p.Arg331Ter)Pathogenic
not provided|Aniridia 1;Irido-corneo-trabecular dysgenesis|Aniridia 1|Albinism or congenital nystagmus
β˜…β˜…β˜†β˜†2025β†’ Residue 331
NM_001368894.2(PAX6):c.205A>T (p.Lys69Ter)Pathogenic
Aniridia 1|not provided|Aniridia 1;Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 69
NM_001368894.2(PAX6):c.275T>A (p.Val92Glu)Pathogenic
Aniridia 1;Irido-corneo-trabecular dysgenesis|PAX6-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 92
NM_001368894.2(PAX6):c.649C>T (p.Arg217Ter)Pathogenic
Aniridia 1|Irido-corneo-trabecular dysgenesis;Aniridia 1|not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 217
NM_001368894.2(PAX6):c.1310A>T (p.Ter437Leu)Pathogenic
Aniridia 1|not provided|8 conditions|Irido-corneo-trabecular dysgenesis;Aniridia 1|Hypertelorism;Nystagmus;Visual impairment|Foveal hypoplasia 1|Sporadic aniridia
β˜…β˜…β˜†β˜†2025β†’ Residue 437
NM_001368894.2(PAX6):c.112C>T (p.Arg38Trp)Pathogenic
Aniridia 1|Aniridia 1;Irido-corneo-trabecular dysgenesis|Coloboma, ocular, autosomal dominant|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 38
NM_001368894.2(PAX6):c.419T>A (p.Val140Asp)Pathogenic
Aniridia, atypical|Irido-corneo-trabecular dysgenesis;Aniridia 1|PAX6-related ocular dysgenesis|7 conditions|Irido-corneo-trabecular dysgenesis;Foveal hypoplasia 1
β˜…β˜…β˜†β˜†2025β†’ Residue 140
NM_001368894.2(PAX6):c.76C>T (p.Arg26Trp)Pathogenic
Aniridia 1|Aniridia 1;Irido-corneo-trabecular dysgenesis|Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 26
NM_001368894.2(PAX6):c.399+1G>APathogenic
not provided|Aniridia 1|Irido-corneo-trabecular dysgenesis;Aniridia 1|PAX6-related disorder
β˜…β˜…β˜†β˜†2025
NM_001368894.2(PAX6):c.109del (p.Ala37fs)Pathogenic
not provided|Aniridia 1;Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 37
NM_001368894.2(PAX6):c.1225+5G>APathogenic
Aniridia 1;Irido-corneo-trabecular dysgenesis|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025
NM_001368894.2(PAX6):c.193G>A (p.Gly65Arg)Pathogenic
Aniridia 1|not provided|Aniridia 1;Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025β†’ Residue 65
NC_000011.10:g.31800857delPathogenic
not provided|Aniridia 1;Irido-corneo-trabecular dysgenesis
β˜…β˜…β˜†β˜†2025
NM_001368894.2(PAX6):c.-128-2delPathogenic
Aniridia 1|Aniridia 1;Irido-corneo-trabecular dysgenesis|Isolated anophthalmia-microphthalmia syndrome
β˜…β˜…β˜†β˜†2025
NM_001368894.2(PAX6):c.959-1G>APathogenic
Aniridia 1|Aniridia 1;Irido-corneo-trabecular dysgenesis|not provided
β˜…β˜…β˜†β˜†2025
NM_001368894.2(PAX6):c.823C>T (p.Arg275Ter)Pathogenic
not provided|Aniridia 1|Aniridia 1;Irido-corneo-trabecular dysgenesis|8 conditions|7 conditions|PAX6-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 275
View on ClinVar β†—
Related Genes
POU5F1Protein interaction100%DCAF7Protein interaction99%FOXC1Protein interaction98%SIX3Protein interaction95%EP300Protein interaction95%WT1Protein interaction91%
Tissue Expression6 tissues
Brain
100%
Liver
6%
Ovary
6%
Lung
5%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
PAX6POU5F1DCAF7FOXC1SIX3EP300WT1
PROTEIN STRUCTURE
Preparing viewer…
PDB6PAX Β· 2.50 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.23Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.12 [0.07–0.23]
RankingsWhere PAX6 stands among ~20K protein-coding genes
  • #677of 20,598
    Most Researched420 Β· top 5%
  • #124of 5,498
    Most Pathogenic Variants434 Β· top 5%
  • #609of 17,882
    Most Constrained (LOEUF)0.23 Β· top 5%
Genes detectedPAX6
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
PAX6 and congenital eye malformations.
PMID: 14561779
Pediatr Res Β· 2003
1.00
2
PAX genes.
PMID: 7919921
Curr Opin Genet Dev Β· 1994
1.00
3
WNT7A and PAX6 define corneal epithelium homeostasis and pathogenesis.
PMID: 25030175
Nature Β· 2014
0.90
4
A positive feedback inhibition of isocitrate dehydrogenase 3Ξ² on paired-box gene 6 promotes Alzheimer-like pathology.
PMID: 38679634
Signal Transduct Target Ther Β· 2024
0.80
5
Lactate promotes H3K18 lactylation in human neuroectoderm differentiation.
PMID: 39562370
Cell Mol Life Sci Β· 2024
0.76