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

• Rett syndrome, congenital variant (115 variants)
• not provided (69 variants)
• FOXG1 disorder (23 variants)
• Inborn genetic diseases (11 variants)
• FOXG1-related disorder (2 variants)
• Abnormality of the nervous system (1 variants)
• Abnormal cerebral morphology (1 variants)
• Rett syndrome (1 variants)
• Neurodevelopmental disorder (1 variants)
• Global developmental delay;Axial hypotonia;Stereotypic movement disorder;Strabismus;Abnormal optic nerve morphology (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			24	180	13	217
missense	32	57	141	43	29	302
nonsense	43	6				49
start loss			1			1
frameshift	82	19	1			102
inframe indel	2	2	18	38	6	66
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			1	7	4	12
Total	159	84	186	268	52

Variants in FOXG1

This is a list of pathogenic ClinVar variants found in the FOXG1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
14-28766942-C-CA			Benign (Nov 19, 2019)
14-28766942-C-CG			Likely benign (Nov 14, 2019)
14-28767011-G-C			Likely benign (Jun 19, 2018)
14-28767055-CT-C			Likely benign (Aug 21, 2019)
14-28767055-C-CT			Likely benign (Aug 15, 2019)
14-28767254-C-G		not specified	Likely benign (Jun 17, 2016)
14-28767262-C-T		not specified	Likely benign (Sep 23, 2016)
14-28767280-A-T		Rett syndrome, congenital variant	Uncertain significance (Aug 30, 2023)
14-28767284-T-TGAACGA		Rett syndrome, congenital variant	Uncertain significance (Sep 22, 2024)
14-28767288-C-T		not specified	Likely benign (Jan 13, 2017)
14-28767289-A-G			Uncertain significance (Dec 03, 2023)
14-28767300-G-A		Rett syndrome, congenital variant	Uncertain significance (Jan 10, 2024)
14-28767301-AAAG-A		Rett syndrome, congenital variant	Uncertain significance (Oct 05, 2023)
14-28767306-G-A		Rett syndrome, congenital variant	Uncertain significance (Dec 17, 2023)
14-28767318-C-T		Rett syndrome, congenital variant	Likely benign (Jan 24, 2020)
14-28767319-C-T		Rett syndrome, congenital variant	Uncertain significance (Feb 08, 2022)
14-28767325-T-C		Rett syndrome, congenital variant	Uncertain significance (May 20, 2023)
14-28767336-C-T		not specified • Rett syndrome, congenital variant	Likely benign (Jul 12, 2022)
14-28767357-G-A		Rett syndrome, congenital variant	Likely benign (Feb 03, 2022)
14-28767360-G-A		Rett syndrome, congenital variant	Likely benign (Oct 29, 2021)
14-28767362-TC-T		Rett syndrome, congenital variant	Pathogenic (May 28, 2019)
14-28767364-C-T			Pathogenic (Sep 01, 2022)
14-28767369-C-T		Rett syndrome, congenital variant	Likely benign (Sep 27, 2022)
14-28767370-G-A			Likely benign (Apr 05, 2021)
14-28767374-A-G		Rett syndrome, congenital variant • Inborn genetic diseases	Conflicting classifications of pathogenicity (Aug 26, 2022)

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
0.944	0.0563	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

Haploinsufficiency Scores

• pHI: 0.404
• ghis: 0.631

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

Mouse Genome Informatics

• Gene name: Foxg1
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; pigmentation phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; immune system phenotype; skeleton phenotype; digestive/alimentary phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); taste/olfaction phenotype; endocrine/exocrine gland phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype

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