FOXE3

Chr 1ADAR

forkhead box E3

Also known as: AAT11, ASGD2, CATC3, CTRCT34, FKHL12, FREAC8

NCBI Gene: 2301 ENSG00000186790 UniProt: Q13461 OMIM: 601094

FOXE3 encodes a lens-specific transcription factor that controls lens epithelial cell growth, proliferation, and differentiation during eye development. Mutations cause anterior segment dysgenesis, congenital cataracts, and congenital primary aphakia, with both autosomal dominant and autosomal recessive inheritance patterns reported. The gene primarily affects ocular development, though some mutations are also associated with familial thoracic aortic aneurysm susceptibility.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This intronless gene belongs to the forkhead family of transcription factors, which is characterized by a distinct forkhead domain. The protein encoded functions as a lens-specific transcription factor and plays an important role in vertebrate lens formation. Mutations in this gene are associated with anterior segment mesenchymal dysgenesis and congenital primary aphakia. [provided by RefSeq, Dec 2009]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

{Aortic aneurysm, familial thoracic 11, susceptibility to}MIM #617349

Anterior segment dysgenesis 2, multiple subtypesMIM #610256

Cataract 34, multiple typesMIM #612968

Clinical highlights

Gene–disease validity (ClinGen)

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype), though the gene is not strongly LoF-constrained in the population — weigh truncating variants against that tolerance.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.61

LOEUF

LOF

Mechanism· G2P

📖

GeneReview available — FOXE3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.61LOEUF

pLI 0.181

Z-score 0.89

OE 0.40 (0.14–1.61)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.57Z-score

OE missense 0.83 (0.69–1.01)

76 obs / 91.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.14–1.61)

0≤0.351.4

Missense OE?0.83 (0.69–1.01)

0≤0.61.4

Synonymous OE?1.18

0≤1.21.6

LoF obs/exp: 1 / 2.5Missense obs/exp: 76 / 91.3Syn Z: -0.95

Background carrier burden — how many people carry a rare variant somewhere in FOXE3?

gnomAD v4 · ~730k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 82

562 rare PASS variants

Rare truncating (LoF)

1 in 2,100

72 rare PASS variants

Rare synonymous (reference)

1 in 120

292 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for FOXE3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~555k	1 in 160	1 in 2,200
South Asian	~43k	1 in 130	1 in 760
Remaining (unassigned)	~30k	1 in 120	1 in 2,700
European (Finnish)	~27k	1 in 280	≈ 1 in 8,500
Admixed American	~22k	1 in 84	1 in 2,100
African / African American	~21k	1 in 120	1 in 1,900
East Asian	~20k	1 in 120	1 in 3,700
Ashkenazi Jewish	~13k	1 in 350	≈ 1 in 5,800
Middle Eastern	~2,879	1 in 89	≈ 1 in 1,600

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): 0 of 1 coding exons well covered in gnomAD exomes; exon 1 marginal. Genomes: all 1.? see exons ↓