FOXG1

forkhead box G1, the group of Forkhead boxes

Basic information

Region (hg38): 14:28764329-28770277

Previous symbols: [ "FKHL2", "FOXG1B", "FKHL4", "FKH2", "FKHL1", "FOXG1C", "FKHL3", "FOXG1A" ]

Links

ENSG00000176165 ∙ NCBI:2290 ∙ OMIM:164874 ∙ HGNC:3811 ∙ Uniprot:P55316 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Rett syndrome, congenital variant (Definitive), mode of inheritance: AD
• FOXG1 disorder (Definitive), mode of inheritance: AD
• Rett syndrome, congenital variant (Strong), mode of inheritance: AD
• FOXG1 disorder (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Rett syndrome, congenital variant	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	18571142; 19578037; 19564653; 20736978; 21441262; 21536641; 21910242; 21953941; 22091895; 22129046; 22258524; 22415763; 22670136

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXG1 gene.

• FOXG1_disorder (718 variants)
• not_provided (266 variants)
• Inborn_genetic_diseases (122 variants)
• not_specified (81 variants)
• FOXG1-related_disorder (35 variants)
• Rett_syndrome (16 variants)
• Intellectual_disability (3 variants)
• Neurodevelopmental_disorder (2 variants)
• Stereotypic_movement_disorder (1 variants)
• Abnormal_cerebral_morphology (1 variants)
• Autism_spectrum_disorder (1 variants)
• Abnormal_optic_nerve_morphology (1 variants)
• Aplasia/Hypoplasia_of_the_corpus_callosum (1 variants)
• Microcephaly (1 variants)
• Severe_intellectual_deficiency (1 variants)
• Axial_hypotonia (1 variants)
• Lissencephaly (1 variants)
• Severe_intellectual_disability (1 variants)
• Seizure (1 variants)
• Neurodevelopmental_abnormality (1 variants)
• Strabismus (1 variants)
• Global_developmental_delay (1 variants)
• See_cases (1 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Combined_oxidative_phosphorylation_defect_type_24 (1 variants)
• Primary_microcephaly (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXG1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000005249.5. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous	1		41	184	23	249
missense	37	75	206	54	33	405
nonsense	45	10				55
start loss			1			1
frameshift	92	25	2			119
splice donor/acceptor (+/-2bp)						0
Total	175	110	250	238	56

Highest pathogenic variant AF is 0.00000985336

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXG1	protein_coding	protein_coding	ENST00000382535	1	3821

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
		0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.49	84	234	0.358	0.0000115	3156
Missense in Polyphen		3	62.181	0.048246		684
Synonymous	-2.38	137	106	1.29	0.00000569	1025
Loss of Function	2.79	0	9.09	0.00	3.97e-7	124

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcription repression factor which plays an important role in the establishment of the regional subdivision of the developing brain and in the development of the telencephalon. {ECO:0000269|PubMed:12657635}.
• Pathway: FoxO signaling pathway - Homo sapiens (human);Tgif disruption of Shh signaling;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.696

Intolerance Scores

• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.42

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Zebrafish Information Network

• Gene name: foxg1a
• Affected structure: microvillous olfactory receptor neuron
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;brain development;aging;negative regulation of transcription, DNA-templated
• Cellular component: nucleus
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;DNA binding;protein binding;sequence-specific DNA binding