FOXO6 encodes a transcriptional activator that binds DNA and regulates gene transcription by RNA polymerase II, with predicted involvement in dendritic spine development. Mutations cause autosomal recessive intellectual disability with microcephaly and seizures. The gene shows moderate constraint to loss-of-function variation (LOEUF 0.67), consistent with its role in neurodevelopment.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.67
Clinical SummaryFOXO6
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.21) despite low pLI — interpret in context.
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ClinVar Variants
11 unique Pathogenic / Likely Pathogenic· 4 VUS of 16 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.67LOEUF
pLI 0.405
Z-score 2.23
OE 0.21 (0.090.67)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.32Z-score
OE missense 0.70 (0.600.82)
110 obs / 156.4 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.21 (0.090.67)
00.351.4
Missense OE0.70 (0.600.82)
00.61.4
Synonymous OE0.80
01.21.6
LoF obs/exp: 2 / 9.4Missense obs/exp: 110 / 156.4Syn Z: 1.30

ClinVar Variant Classifications

16 submitted variants in ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic3
VUS4
Likely Benign1
8
Pathogenic
3
Likely Pathogenic
4
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
8
Likely Pathogenic
3
VUS
4
Likely Benign
1
Benign
0
Total16

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FOXO6 · 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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