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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
FOXG1
forkhead box G1
Chromosome 14 Β· 14q12
NCBI Gene: 2290Ensembl: ENSG00000176165.13HGNC: HGNC:3811UniProt: P55316
120PubMed Papers
21Diseases
0Drugs
277Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
protein bindingnegative regulation of DNA-templated transcriptionsequence-specific double-stranded DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificFOXG1 disordergenetic disorderRett syndromeNeurodevelopmental disorder
✦AI Summary

FOXG1 (forkhead box G1) is a transcription repressor that plays a critical role in establishing regional brain subdivisions and telencephalic development 1. As a sequence-specific DNA-binding transcription factor, FOXG1 regulates gene expression through RNA polymerase II-dependent mechanisms and chr14 remodeling in the nucleus. FOXG1 demonstrates pleiotropic effects on cell fate specification, with particular importance in Layer 6 corticothalamic neuron development and the regulation of GABAergic versus glutamatergic neuron differentiation 23. Dysregulation of FOXG1 expression has been implicated in neurodevelopmental disorders. Pathogenic variants in FOXG1 are associated with developmental epileptic encephalopathy, with all identified mutations being de novo 4. FOXG1 mutations cause Rett syndrome congenital variant and contribute to autism spectrum disorder phenotypes, where FOXG1 overexpression drives overproduction of GABAergic neurons and correlates with symptom severity 3. Additionally, FOXG1-related disorders present with hyperkinetic movement abnormalities including chorea and stereotypies in early childhood 56. These findings establish FOXG1 as essential for normal cortical development and suggest that precise dosage regulation is critical for proper neurodevelopmental outcomes.

Sources cited
1
FOXG1 is a member of the FOX transcription factor family; FOX gene deregulation leads to congenital disorders
PMID: 15492844
2
FOXG1 shows pleiotropic effects and tightly regulates distinct networks essential for cell fate specification of Layer 6 corticothalamic neurons
PMID: 38772369
3
FOXG1 overexpression causes overproduction of GABAergic inhibitory neurons and is positively correlated with autism spectrum disorder symptom severity
PMID: 26186191
4
All variants identified in FOXG1 were de novo in a cohort of 8565 patients with epilepsy and neurodevelopmental disorders
PMID: 29655203
5
FOXG1-related disorders present with chorea and stereotypies as prominent hyperkinetic movement features in children
PMID: 36054588
6
FOXG1 mutations should be considered in younger children presenting with chorea
PMID: 32776155
Disease Associationsβ“˜21
FOXG1 disorderOpen Targets
0.81Strong
genetic disorderOpen Targets
0.54Moderate
Rett syndromeOpen Targets
0.54Moderate
Neurodevelopmental disorderOpen Targets
0.43Moderate
mathematical abilityOpen Targets
0.41Moderate
placenta praeviaOpen Targets
0.37Weak
undetermined early-onset epileptic encephalopathyOpen Targets
0.37Weak
StrabismusOpen Targets
0.34Weak
Abnormality of the nervous systemOpen Targets
0.34Weak
Global developmental delayOpen Targets
0.34Weak
respiratory tract infectious disorderOpen Targets
0.33Weak
Abnormal optic nerve morphologyOpen Targets
0.33Weak
Axial hypotoniaOpen Targets
0.33Weak
stereotypic movement disorderOpen Targets
0.33Weak
Severe intellectual disabilityOpen Targets
0.33Weak
corneal ulcerOpen Targets
0.33Weak
intelligenceOpen Targets
0.31Weak
obesityOpen Targets
0.31Weak
liver diseaseOpen Targets
0.29Weak
schizophreniaOpen Targets
0.29Weak
Rett syndrome congenital variantUniProt
Pathogenic Variants277
NM_005249.5(FOXG1):c.706A>G (p.Asn236Asp)Likely pathogenic
not provided|FOXG1 disorder
β˜…β˜…β˜…β˜†2025β†’ Residue 236
NM_005249.5(FOXG1):c.670G>A (p.Gly224Ser)Likely pathogenic
not provided|FOXG1 disorder|Rett syndrome
β˜…β˜…β˜…β˜†2024β†’ Residue 224
NM_005249.5(FOXG1):c.748G>A (p.Gly250Ser)Likely pathogenic
not provided|FOXG1 disorder
β˜…β˜…β˜…β˜†2024β†’ Residue 250
NM_005249.5(FOXG1):c.701C>T (p.Ser234Phe)Pathogenic
Inborn genetic diseases|FOXG1 disorder
β˜…β˜…β˜…β˜†2024β†’ Residue 234
NM_005249.5(FOXG1):c.573G>A (p.Met191Ile)Likely pathogenic
not provided|FOXG1 disorder
β˜…β˜…β˜…β˜†2023β†’ Residue 191
NM_005249.5(FOXG1):c.565C>G (p.Leu189Val)Likely pathogenic
FOXG1 disorder
β˜…β˜…β˜…β˜†2023β†’ Residue 189
NM_005249.5(FOXG1):c.620T>C (p.Ile207Thr)Likely pathogenic
Inborn genetic diseases|FOXG1 disorder|not provided|not specified
β˜…β˜…β˜…β˜†2023β†’ Residue 207
NM_005249.5(FOXG1):c.685A>C (p.Ile229Leu)Likely pathogenic
not provided|FOXG1 disorder
β˜…β˜…β˜…β˜†2022β†’ Residue 229
NM_005249.5(FOXG1):c.460dup (p.Glu154fs)Pathogenic
not provided|FOXG1 disorder|Inborn genetic diseases|Abnormal cerebral morphology|FOXG1-related disorder
β˜…β˜…β˜…β˜†2021β†’ Residue 154
NM_005249.5(FOXG1):c.177_186dup (p.Pro63fs)Pathogenic
not provided|FOXG1 disorder
β˜…β˜…β˜…β˜†2021β†’ Residue 63
NM_005249.5(FOXG1):c.561C>A (p.Asn187Lys)Pathogenic
not provided|Inborn genetic diseases|FOXG1 disorder
β˜…β˜…β˜…β˜†2021β†’ Residue 187
NM_005249.5(FOXG1):c.256del (p.Gln86fs)Pathogenic
FOXG1 disorder|not provided|Rett syndrome
β˜…β˜…β˜…β˜†2021β†’ Residue 86
NM_005249.5(FOXG1):c.799G>A (p.Gly267Ser)Pathogenic
FOXG1 disorder|not provided
β˜…β˜…β˜…β˜†2021β†’ Residue 267
NM_005249.5(FOXG1):c.506del (p.Gly169fs)Pathogenic
Inborn genetic diseases|not provided|FOXG1 disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 169
NM_005249.5(FOXG1):c.651C>G (p.Tyr217Ter)Pathogenic
not provided|FOXG1 disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 217
NM_005249.5(FOXG1):c.921C>G (p.Tyr307Ter)Pathogenic
FOXG1 disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 307
NM_005249.5(FOXG1):c.624C>A (p.Tyr208Ter)Pathogenic
FOXG1 disorder|Global developmental delay;Axial hypotonia;Stereotypic movement disorder;Strabismus;Abnormal optic nerve morphology
β˜…β˜…β˜†β˜†2025β†’ Residue 208
NM_005249.5(FOXG1):c.571ATG[1] (p.Met192del)Pathogenic
FOXG1 disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 192
NM_005249.5(FOXG1):c.256dup (p.Gln86fs)Pathogenic
FOXG1 disorder|not provided|Abnormality of the nervous system|FOXG1-related disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 86
NM_005249.5(FOXG1):c.694A>G (p.Asn232Asp)Pathogenic
FOXG1 disorder
β˜…β˜…β˜†β˜†2025β†’ Residue 232
View on ClinVar β†—
Related Genes
MATCAP1Shared pathway100%VCX3BShared pathway100%FOXR1Shared pathway100%DNAJC30Shared pathway100%CA10Shared pathway100%VCX3AShared pathway100%
Tissue Expression6 tissues
Brain
100%
Ovary
2%
Bone Marrow
0%
Liver
0%
Lung
0%
Heart
0%
Gene Interaction Network
Click a node to explore
FOXG1MATCAP1VCX3BFOXR1DNAJC30CA10VCX3A
PROTEIN STRUCTURE
Preparing viewer…
PDB7CBY Β· 1.65 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.36Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.14 [0.06–0.36]
RankingsWhere FOXG1 stands among ~20K protein-coding genes
  • #3,917of 20,598
    Most Researched120 Β· top quartile
  • #227of 5,498
    Most Pathogenic Variants277 Β· top 5%
  • #1,609of 17,882
    Most Constrained (LOEUF)0.36 Β· top 10%
Genes detectedFOXG1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Human FOX gene family (Review).
PMID: 15492844
Int J Oncol Β· 2004
1.00
2
CDKL5 deficiency disorder: clinical features, diagnosis, and management.
PMID: 35483386
Lancet Neurol Β· 2022
0.90
3
Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.
PMID: 29655203
Epilepsia Β· 2018
0.80
4
FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders.
PMID: 26186191
Cell Β· 2015
0.70
5
The Genetic Landscape of Complex Childhood-Onset Hyperkinetic Movement Disorders.
PMID: 36054588
Mov Disord Β· 2022
0.60