Fetal anomalies
Gene: PAX6

PAX6 (paired box 6)
EnsemblGeneIds (GRCh38): ENSG00000007372
EnsemblGeneIds (GRCh37): ENSG00000007372
OMIM: 607108, Gene2Phenotype
PAX6 is in 22 panels

2 reviews

Luke Stuart (Genomics England Curator)

Green List (high evidence)

Biallelic PAX6 variants are associated with severe congenital malformation including structural brain anomalies and aniridia. The paucity of patients reports reflects embryonic/ perinatal lethality associated with biallelic PAX6 loss of function.

Glaser et al. 1994; PMID 7951315: A proband with compound heterozygous nonsense variants, c.607C>T (p.Arg203Ter) and c.1058C>G (p.Ser353Ter), presented with anophthalmia, microcephaly, complete agenesis of the corpus callosum and olfactory bulbs, hypoplasia of the cerebellum and pons, and died in the neonatal period.

Solomon et al., 2010 (PMID 19876904): A surviving patient with compound heterozygous mutations in PAX6 presented with microphthalmia, neonatal diabetes mellitus, hypopituitarism, and microcephaly, as well as trisomy 21. The patient inherited a missense mutation affecting the paired domain from the father (c.112C>T, p.Arg38Trp), who had microcornea and severe cataracts, and a nonsense mutation in HD from the mother (c.718C>T, p.Arg240Ter), who presented with classical familial aniridia. Complex brain anomalies including absent corpus callosum, hypoplastic brainstem, near-absent olfactory bulbs, and polymicrogyria were noted.

Schmidt-Sidor et al., 2009 (PMID 20054790) described a stillborn fetus; PAX6 c.117_128del12 (affecting the paired domain) and a frameshift variant, c.112delC, were identified in compound heterozygosity; autopsy revealed major CNS abnormalities including complete agenesis of the corpus callosum, cortical malformations and various cerebellar anomalies including cerebellar dysplasia; a similar phenotype was observed in a subsequent pregnancy.

This severe CNS malformation phenotype is recapitulated in the Sey (Small eye) mouse, which carries a PAX6 LoF point mutation c.622G>T (p.Gly208Ter) (Schmahl et al., 1993; PMID 8213068; Quinn et al., 2007; PMID 16979618)); Pax6 is produced in cerebellar granule cells and that PAX6 influences the morphogenesis of the whole cerebellum; homozygous Pax6Sey/Sey mice exhibit severe brain malformations, including cerebellar abnormalities, and die perinatally, whereas heterozygous Pax6Sey/+ mice survive and show developmental defects consistent with PAX6 haploinsufficiency.

3 unrelated patients are reported and the biallelic Sey mouse model recapitulates the human phenotype. Thus MOI comprising BOTH monoallelic and biallelic is proposed for the fetal anomalies panel.
Created: 11 Sep 2026, 4:18 p.m. | Last Modified: 11 Sep 2026, 4:18 p.m.

Panel Version: 8.7

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Corpus callosum, agenesis of (MONDO:0009022)

Publications

Created: 11 Sep 2026, 4:18 p.m.
Last Modified: 11 Sep 2026, 4:18 p.m.
Panel version: 8.7

Rebecca Foulger (Genomics England curator)

Green List (high evidence)

This gene was re-reviewed in a consistency check by Anna de Burca (Genomics England Clinical Team), and at a Fetal Working Group call on July 19th 2019 by Lyn Chitty, Anna de Burca, Richard Scott, Rhiannon Mellis, Rebecca Foulger and Ellen McDonagh. Outcome of review: Although we wouldn't include Peters anomaly alone on the panel, you can get cataracts with Peters anomaly and therefore include PAX6 and CYP1B1 on this basis.
Created: 25 Jul 2019, 8:04 a.m. | Last Modified: 25 Jul 2019, 8:04 a.m.

Panel Version: 0.311

This gene and phenotype were reviewed during meetings at Great Ormond Street hospital in March and April 2019. Clinical review and curation was performed by Lyn Chitty, Anna de Burca, Rhiannon Mellis, Richard Scott, Ellen McDonagh and Rebecca Foulger. Outcome of review: Phenotype is not fetally-relevant. Action taken: Demoted PAX6 gene rating from Green to Red.
Created: 30 Apr 2019, 8:24 a.m.

DDG2P rating in original PAGE list: Confirmed for KERATITIS HEREDITARY, Confirmed for COLOBOMA OF OPTIC NERVE, Confirmed for PETERS ANOMALY, Confirmed for FOVEAL HYPOPLASIA, Confirmed for BILATERAL OPTIC NERVE HYPOPLASIA, Confirmed for ANIRIDIA and Confirmed for ANIRIDIA CEREBELLAR ATAXIA AND MENTAL DEFICIENCY.
Created: 11 Dec 2018, 9:05 a.m.

In the original PAGE file, MOP listed as LOF for KERATITIS HEREDITARYX, COLOBOMA OF OPTIC NERVE, FOVEAL HYPOPLASIA, BILATERAL OPTIC NERVE HYPOPLASIA, ANIRIDIA and ANIRIDIA CEREBELLAR ATAXIA AND MENTAL DEFICIENCY. MOP listed as Uncertain for PETERS ANOMALY.
Created: 8 Nov 2018, 4:45 p.m.

Created: 8 Nov 2018, 4:45 p.m.

Panel version: 0.311

Details

Mode of Inheritance

MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Sources

Expert Review Green
PAGE DD-Gene2Phenotype

Phenotypes

COLOBOMA OF OPTIC NERVE
ANIRIDIA
BILATERAL OPTIC NERVE HYPOPLASIA
ANIRIDIA CEREBELLAR ATAXIA AND MENTAL DEFICIENCY
KERATITIS HEREDITARY
PETERS ANOMALY
FOVEAL HYPOPLASIA

OMIM

607108

Clinvar variants

Variants in PAX6

Penetrance

None

Panels with this gene