FOXG1

Chr 14

forkhead box G1

Also known as: BF1, BF2, FHKL3, FKH2, FKHL1, FKHL2, FKHL3, FKHL4

NCBI Gene: 2290ENSG00000176165UniProt: P55316

This locus encodes a member of the fork-head transcription factor family. The encoded protein, which functions as a transcriptional repressor, is highly expressed in neural tissues during brain development. Mutations at this locus have been associated with Rett syndrome and a diverse spectrum of neurodevelopmental disorders defined as part of the FOXG1 syndrome. This gene is disregulated in many types of cancer and is the target of multiple microRNAs that regulate the proliferation of tumor cells. [provided by RefSeq, Jul 2020]

Primary Disease Associations & Inheritance

UniProtRett syndrome congenital variant
0
ClinVar variants
0
Pathogenic / LP
0.94
pLI score· haploinsufficient
1
Active trials
Clinical Summary— FOXG1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.94). One damaged copy is likely sufficient to cause disease.
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (2)

clinvarCount: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.33LOEUF
pLI 0.944
Z-score 2.79
OE 0.00 (0.00–0.33)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.49Z-score
OE missense 0.36 (0.30–0.43)
84 obs / 234.3 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.33)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.36 (0.30–0.43)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.29
0≤1.21.6
LoF obs/exp: 0 / 9.1Missense obs/exp: 84 / 234.3Syn Z: -2.38

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FOXG1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FOXG1-related congenital variant of Rett syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
Pérez-Dueñas B et al.·Mov Disord
2022
Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.
Lindy AS et al.·Epilepsia
2018Cohort
Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.
McKnight D et al.·Hum Mutat
2022
De novo mutations in moderate or severe intellectual disability.
Hamdan FF et al.·PLoS Genet
2014
FOXG1 promotes aging inner ear hair cell survival through activation of the autophagy pathway.
He ZH et al.·Autophagy
2021
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
FOXG1-Related Syndrome: From Clinical to Molecular Genetics and Pathogenic Mechanisms.
Wong LC et al.·Int J Mol Sci
2019Review
Rett and Rett-related disorders: Common mechanisms for shared symptoms?
D'Mello SR·Exp Biol Med (Maywood)
2023Review
Epilepsy in Rett syndrome, and CDKL5- and FOXG1-gene-related encephalopathies.
Guerrini R et al.·Epilepsia
2012Review
Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective.
Akol I et al.·Int J Mol Sci
2022Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
FOXG1 Syndrome

Phase 1/2 Study of FRF-001, an AAV-9 Gene Therapy, in Patients With FOXG1 Syndrome (FS)

NOT YET RECRUITING
NCT07293546Phase PHASE1, PHASE2FOXG1 Research FoundationStarted 2026-04
FRF-001

External Resources

Links to major genomics databases and tools