Structural eye disease

Gene: FOXD3

Red List (low evidence)

Comment on list classification: As the evidence for the association of FOXD3 gene with eye disorder is disputed, this gene should be considered for demotion to red rating in the next GMS update.

Created: 16 Oct 2025, 1:48 p.m. | Last Modified: 16 Oct 2025, 2:09 p.m.

Panel Version: 4.34

Monoallelic variants in FOXD3 gene have been associated with aniridia (MONDO:0019172) with 'Disputed' rating by the Glaucoma and Neuro-Ophthalmology expert panel in ClinGen (https://search.clinicalgenome.org/CCID:004877)

Although there are four unrelated families reported with anterior segment dysgenesis/Peters anomaly/aniridia and identified with four different variants in FOXD3 gene from one publication (PMID:22815627), all four variants are found at high population frequencies in gnomAD v4.1.0. In addition, there are neither any further reports of published human cases or nor any functional evidence or animal models in support of the association of this gene with this phenotype.

This gene has been associated with 'FOXD3-related anterior segment dysgenesis' phenotype on the Eye panel of Gene2Phenotype with 'limited' rating. However, this gene is not associated with any relevant eye phenotype in OMIM (last accessed on 16 October 2025).

Created: 16 Oct 2025, 1:47 p.m. | Last Modified: 16 Oct 2025, 1:47 p.m.

Panel Version: 4.33

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
aniridia, MONDO:0019172

Publications

• 22815627

Green List (high evidence)

DB Kloss et al. 2012: Five families with anterior segment disorders. Reported variants are missense

Created: 19 Jun 2019, 3:32 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
aniridia; Peters anomaly; Anterior segment dysgenesis

Publications

• 22815627

Mode of pathogenicity
Other - please provide details in the comments

Green List (high evidence)

Submitted on behalf of Professor Nicola Ragge (Wessex and West Midlands GLH). DB Kloss et al. 2012: Five families with anterior segment disorders. Reported variants are missense

Created: 17 Apr 2019, 3:30 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
aniridia; Peters anomaly; Anterior segment dysgenesis

Publications

• 22815627

Mode of pathogenicity
Other - please provide details in the comments