FOXO1

Chr 13Somatic

forkhead box O1

Also known as: FKH1, FKHR, FOXO1A

NCBI Gene: 2308ENSG00000150907UniProt: Q12778OMIM: 136533

FOXO1 encodes a forkhead transcription factor that regulates metabolic homeostasis, glucose metabolism, and cell survival in response to insulin signaling and oxidative stress. Somatic translocations involving FOXO1 cause alveolar rhabdomyosarcoma, a malignant soft tissue tumor that typically affects children and adolescents. The gene is highly constrained against loss-of-function variants (pLI 0.997), indicating it is essential for normal cellular function.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismSomaticLOEUF 0.171 OMIM phenotype
Clinical Summary— FOXO1
⚡
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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ClinVar Variants
46 unique Pathogenic / Likely Pathogenic· 76 VUS of 146 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
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GeneReview available — FOXO1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 0.997
Z-score 3.86
OE 0.00 (0.00–0.17)
Highly constrained

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

Missense Constraint
1.71Z-score
OE missense 0.72 (0.65–0.81)
221 obs / 304.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.00–0.17)
0≤0.351.4
Missense OE0.72 (0.65–0.81)
0≤0.61.4
Synonymous OE1.07
0≤1.21.6
LoF obs/exp: 0 / 17.3Missense obs/exp: 221 / 304.9Syn Z: -0.62
DN
0.3296th %ile
GOF
0.2796th %ile
LOF
0.85top 5%

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

LOFprediction above median · LOEUF 0.17

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

146 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic46
VUS76
Likely Benign7
Benign3
46
Pathogenic
76
VUS
7
Likely Benign
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
46
0
46
Likely Pathogenic
0
0
0
0
0
VUS
0
70
6
0
76
Likely Benign
0
4
0
3
7
Benign
0
0
1
2
3
Total074535132

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FOXO1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients