FOXP2

forkhead box P2, the group of MicroRNA protein coding host genes|Forkhead boxes

Basic information

Region (hg38): 7:114086326-114693772

Previous symbols: [ "TNRC10", "SPCH1" ]

Links

ENSG00000128573 ∙ NCBI:93986 ∙ OMIM:605317 ∙ HGNC:13875 ∙ Uniprot:O15409 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• childhood apraxia of speech (Supportive), mode of inheritance: AD
• specific language disorder (Definitive), mode of inheritance: AD
• childhood apraxia of speech (Strong), mode of inheritance: AD
• childhood apraxia of speech (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Speech-language disorder 1	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	Musculoskeletal; Neurologic	3265313; 11586359; 15326624; 15877281; 17033973; 16470794; 20301499; 22106036; 22105961; 22144704
Paternal deletions are associated with Russell-Silver syndrome, and may be related to speech-language involvement in the condition

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXP2 gene.

• Childhood apraxia of speech (157 variants)
• not provided (117 variants)
• Inborn genetic diseases (58 variants)
• not specified (20 variants)
• FOXP2-related condition (8 variants)
• Lung adenocarcinoma (3 variants)
• See cases (2 variants)
• Squamous cell carcinoma (1 variants)
• Intellectual disability (1 variants)
• 7 conditions (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXP2 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			6	29	4	39
missense	1	2	55	11	2	71
nonsense	14	7				21
start loss						0
frameshift	8	3				11
inframe indel			2	13		15
splice donor/acceptor (+/-2bp)	1	1				2
splice region			9	4	1	14
non coding			52	7	59	118
Total	24	13	115	60	65

Highest pathogenic variant AF is 0.00000658

Variants in FOXP2

This is a list of pathogenic ClinVar variants found in the FOXP2 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-114415036-A-G		Childhood apraxia of speech	Uncertain significance (Jan 13, 2018)
7-114415078-C-T		Childhood apraxia of speech	Uncertain significance (Jan 13, 2018)
7-114415081-A-C		Childhood apraxia of speech	Uncertain significance (Jan 12, 2018)
7-114415149-C-A		Childhood apraxia of speech	Uncertain significance (Jan 12, 2018)
7-114415201-T-C		Childhood apraxia of speech	Conflicting classifications of pathogenicity (Aug 01, 2022)
7-114415272-G-A		Childhood apraxia of speech	Benign (Jan 12, 2018)
7-114415355-G-A		Childhood apraxia of speech	Uncertain significance (Jan 12, 2018)
7-114415357-G-T		Childhood apraxia of speech	Benign (Jan 12, 2018)
7-114426522-A-G		Childhood apraxia of speech	Uncertain significance (Sep 27, 2018)
7-114426532-A-G		Inborn genetic diseases	Likely benign (Apr 04, 2019)
7-114426561-A-T		Childhood apraxia of speech • Inborn genetic diseases • FOXP2-related disorder	Conflicting classifications of pathogenicity (Mar 01, 2024)
7-114426563-A-G		Childhood apraxia of speech • Inborn genetic diseases	Uncertain significance (Jan 08, 2024)
7-114426600-G-A		Inborn genetic diseases	Uncertain significance (Nov 07, 2018)
7-114426617-T-C		Inborn genetic diseases	Likely benign (Dec 19, 2023)
7-114426635-T-C		Childhood apraxia of speech	Uncertain significance (Jan 13, 2018)
7-114426636-C-G		Inborn genetic diseases • FOXP2-related disorder	Uncertain significance (Aug 04, 2023)
7-114426642-T-C		Childhood apraxia of speech	Uncertain significance (Sep 27, 2018)
7-114426665-C-T		Inborn genetic diseases	Likely benign (Sep 26, 2017)
7-114426676-G-A		Childhood apraxia of speech	Uncertain significance (Jan 13, 2018)
7-114534631-A-G		Childhood apraxia of speech	Uncertain significance (Jan 13, 2018)
7-114534645-T-G		Inborn genetic diseases	Pathogenic (Jan 18, 2017)
7-114534647-C-G		Childhood apraxia of speech	Uncertain significance (Jan 13, 2018)
7-114534719-C-G		Childhood apraxia of speech	Uncertain significance (Apr 27, 2017)
7-114550367-C-T		Childhood apraxia of speech	Uncertain significance (Jul 03, 2020)
7-114570759-T-C			Benign (Jun 18, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXP2	protein_coding	protein_coding	ENST00000408937	17	607446

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000570	125697	0	12	125709	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.90	276	380	0.726	0.0000195	4865
Missense in Polyphen		31	60.052	0.51622		768
Synonymous	-0.986	153	138	1.11	0.00000724	1358
Loss of Function	6.06	6	54.1	0.111	0.00000295	524

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000510	0.000489
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000265	0.0000264
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor that may play a role in the specification and differentiation of lung epithelium. May also play a role in developing neural, gastrointestinal and cardiovascular tissues. Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential. Plays a role in synapse formation by regulating SRPX2 levels. Involved in neural mechanisms mediating the development of speech and language.
• Disease: DISEASE: Speech-language disorder 1 (SPCH1) [MIM:602081]: A disorder characterized by severe orofacial dyspraxia resulting in largely incomprehensible speech. Affected individuals have severe impairment in the selection and sequencing of fine orofacial movements which are necessary for articulation, and deficits in several facets of grammatical skills and language processing, such as the ability to break up words into their constituent phonemes. {ECO:0000269|PubMed:11586359}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=A chromosomal aberration involving FOXP2 is a cause of severe speech and language impairment. Translocation t(5;7)(q22;q31.2).
• Pathway: Pathways Affected in Adenoid Cystic Carcinoma (Consensus)

Recessive Scores

• pRec: 0.651

Intolerance Scores

• loftool: 0.117
• rvis_EVS: -0.82
• rvis_percentile_EVS: 11.68

Haploinsufficiency Scores

• pHI: 0.911
• hipred: Y
• hipred_score: 0.793
• ghis: 0.572

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.968

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxp2
• Phenotype: muscle phenotype; craniofacial phenotype; cellular phenotype; homeostasis/metabolism phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); 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; digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); respiratory system phenotype; 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); 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)

Zebrafish Information Network

• Gene name: foxp2
• Affected structure: central nervous system development
• Phenotype tag: abnormal
• Phenotype quality: disrupted

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;positive regulation of mesenchymal cell proliferation;skeletal muscle tissue development;post-embryonic development;cerebellum development;caudate nucleus development;putamen development;cerebral cortex development;response to testosterone;vocal learning;camera-type eye development;negative regulation of transcription, DNA-templated;lung alveolus development;smooth muscle tissue development;righting reflex;positive regulation of epithelial cell proliferation involved in lung morphogenesis;innate vocalization behavior
• Cellular component: nucleus
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;protein binding;identical protein binding;protein homodimerization activity;sequence-specific DNA binding;metal ion binding;protein heterodimerization activity;androgen receptor binding