FOXF1

Chr 16AD

forkhead box F1

Also known as: ACDMPV, FKHL5, FREAC1

FOXF1 encodes a forkhead transcription factor that activates lung-specific genes and regulates pulmonary development. Mutations cause alveolar capillary dysplasia with misalignment of pulmonary veins, a severe neonatal respiratory disorder with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI 0.96, LOEUF 0.30), reflecting its critical role in pulmonary vascular development.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismADLOEUF 0.301 OMIM phenotype
Clinical SummaryFOXF1
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.96). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.30LOEUF
pLI 0.958
Z-score 2.92
OE 0.00 (0.000.30)
Highly constrained

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

Missense Constraint
1.09Z-score
OE missense 0.79 (0.690.90)
161 obs / 204.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.30)
00.351.4
Missense OE0.79 (0.690.90)
00.61.4
Synonymous OE1.28
01.21.6
LoF obs/exp: 0 / 9.9Missense obs/exp: 161 / 204.9Syn Z: -2.15
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveFOXF1-related alveolar capillary dysplasia with misalignment of pulmonary veinsLOFAD
DN
0.4090th %ile
GOF
0.2597th %ile
LOF
0.84top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.30

Literature Evidence

LOFPrenatal Diagnosis of Cystic Hygroma related to a Deletion of 16q24.1 with Haploinsufficiency of FOXF1 and FOXC2 Genes.PMID:23074687

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

FOXF1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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