PAX6

Chr 11AD

paired box 6

Also known as: AN, AN1, AN2, ASGD5, D11S812E, FVH1, MGDA, WAGR

PAX6 encodes a transcription factor containing paired box and homeobox domains that regulates gene expression essential for eye and neural tissue development. Mutations cause autosomal dominant ocular disorders including aniridia, anterior segment dysgenesis, foveal hypoplasia, microphthalmia/coloboma, and optic nerve abnormalities through loss of function mechanisms. The protein is highly intolerant to loss-of-function variants, reflecting its critical role in eye development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismADLOEUF 0.179 OMIM phenotypes
Clinical SummaryPAX6
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Gene-Disease Validity (ClinGen)
PAX6-related ocular dysgenesis · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — PAX6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 1.000
Z-score 4.74
OE 0.04 (0.010.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.82Z-score
OE missense 0.49 (0.420.57)
120 obs / 243.8 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.04 (0.010.17)
00.351.4
Missense OE0.49 (0.420.57)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 1 / 28.1Missense obs/exp: 120 / 243.8Syn Z: -0.85
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitivePAX6-related Peters anomalyOTHERAD
definitivePAX6-related aniridiaLOFAD
DN
0.5869th %ile
GOF
0.3887th %ile
LOF
0.79top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · LOEUF 0.17

Literature Evidence

LOFIn humans, haploinsufficiency of either SOX2 or PAX6 is associated with microphthalmia, anophthalmia or aniridia.PMID:21205789

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PAX6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
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