FOXP1

forkhead box P1, the group of Forkhead boxes|MicroRNA protein coding host genes

Basic information

Region (hg38): 3:70954692-71583978

Links

ENSG00000114861 ∙ NCBI:27086 ∙ OMIM:605515 ∙ HGNC:3823 ∙ Uniprot:Q9H334 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• intellectual disability-severe speech delay-mild dysmorphism syndrome (Definitive), mode of inheritance: AD
• intellectual disability-severe speech delay-mild dysmorphism syndrome (Definitive), mode of inheritance: AD
• intellectual disability-severe speech delay-mild dysmorphism syndrome (Moderate), mode of inheritance: AD
• intellectual disability-severe speech delay-mild dysmorphism syndrome (Strong), mode of inheritance: AD
• intellectual disability-severe speech delay-mild dysmorphism syndrome (Definitive), mode of inheritance: AD
• congenital heart disease (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Intellectual developmental disorder with language impairment with or without autistic features	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	20571508; 20950788; 21572417; 22521361

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FOXP1 gene.

• not provided (496 variants)
• Intellectual disability-severe speech delay-mild dysmorphism syndrome (115 variants)
• Inborn genetic diseases (82 variants)
• Intellectual Disability with Language Impairment and Autistic Features (48 variants)
• not specified (36 variants)
• Intellectual disability (10 variants)
• FOXP1-related condition (8 variants)
• See cases (5 variants)
• Congenital cerebellar hypoplasia (2 variants)
• Developmental disorder (2 variants)
• Rare genetic intellectual disability (2 variants)
• Intellectual disability-severe speech delay-mild dysmorphism syndrome;Cerebellar vermis hypoplasia (1 variants)
• Intellectual disability;Seizure (1 variants)
• Hypoplastic left heart syndrome 1;Aortic valve atresia;Mitral atresia disorder (1 variants)
• Cerebellar vermis hypoplasia;Intellectual disability-severe speech delay-mild dysmorphism syndrome (1 variants)
• Intellectual disability;Anterior creases of earlobe;Delayed speech and language development;Strabismus;Glabellar hemangioma (1 variants)
• Autism;Intellectual disability (1 variants)
• Neurodevelopmental disorder (1 variants)
• Autism spectrum disorder (1 variants)
• Pulmonary atresia with ventricular septal defect;Visceral heterotaxy;Familial atrioventricular septal defect;Single Ventricle Defect (1 variants)
• Atrial septal defect 1 (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FOXP1 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			5	95	4	104
missense	6	17	163	34	7	227
nonsense	24	4	1			29
start loss			1			1
frameshift	35	12				47
inframe indel	1		10			11
splice donor/acceptor (+/-2bp)	13	10	1			24
splice region	2	4	12	21	1	40
non coding			48	76	46	170
Total	79	43	229	205	57

Variants in FOXP1

This is a list of pathogenic ClinVar variants found in the FOXP1 region.

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

Position	Type	Phenotype	Significance	ClinVar
3-70955217-AT-A		Intellectual Disability with Language Impairment and Autistic Features	Conflicting classifications of pathogenicity (May 01, 2022)
3-70955524-GA-G		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955569-A-AT		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955570-G-GT		Intellectual Disability with Language Impairment and Autistic Features	Benign (Jun 14, 2016)
3-70955638-T-TA		Intellectual Disability with Language Impairment and Autistic Features	Likely benign (Jun 14, 2016)
3-70955826-A-ACG		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955830-G-GCACACA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-G-ACACACACA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-G-ACACACACACA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-GCA-G		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-GCACA-G		Intellectual Disability with Language Impairment and Autistic Features	Conflicting classifications of pathogenicity (Mar 01, 2024)
3-70955832-G-GCA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-G-GCACA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-G-GCGCACA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955832-G-GCACACACA		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955834-A-G			Benign (Feb 01, 2024)
3-70955843-CA-C		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70955943-A-AG		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70956054-GT-G		Intellectual Disability with Language Impairment and Autistic Features	Conflicting classifications of pathogenicity (Jul 01, 2023)
3-70956409-A-AT		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70956414-TC-T		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70956415-C-CT		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70956489-G-GT		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70956764-TTTTTTTTTTA-T		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)
3-70957041-ATC-A		Intellectual Disability with Language Impairment and Autistic Features	Uncertain significance (Jun 14, 2016)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FOXP1	protein_coding	protein_coding	ENST00000491238	16	629297

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000162	125736	0	12	125748	0.0000477

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.28	247	370	0.667	0.0000206	4483
Missense in Polyphen		23	88.874	0.25879		1002
Synonymous	-1.69	171	145	1.18	0.00000928	1276
Loss of Function	5.75	3	44.3	0.0678	0.00000240	439

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.000229	0.000229
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional repressor (PubMed:18347093, PubMed:26647308). Can act with CTBP1 to synergistically repress transcription but CTPBP1 is not essential (By similarity). Plays an important role in the specification and differentiation of lung epithelium. Acts cooperatively with FOXP4 to regulate lung secretory epithelial cell fate and regeneration by restricting the goblet cell lineage program; the function may involve regulation of AGR2. Essential transcriptional regulator of B-cell development. Involved in regulation of cardiac muscle cell proliferation. Involved in the columnar organization of spinal motor neurons. Promotes the formation of the lateral motor neuron column (LMC) and the preganglionic motor column (PGC) and is required for respective appropriate motor axon projections. The segment-appropriate generation of spinal chord motor columns requires cooperation with other Hox proteins. Can regulate PITX3 promoter activity; may promote midbrain identity in embryonic stem cell-derived dopamine neurons by regulating PITX3. Negatively regulates the differentiation of T follicular helper cells T(FH)s. Involved in maintenance of hair follicle stem cell quiescence; the function probably involves regulation of FGF18 (By similarity). Represses transcription of various pro-apoptotic genes and cooperates with NF-kappa B-signaling in promoting B-cell expansion by inhibition of caspase-dependent apoptosis (PubMed:25267198). Binds to CSF1R promoter elements and is involved in regulation of monocyte differentiation and macrophage functions; repression of CSF1R in monocytes seems to involve NCOR2 as corepressor (PubMed:15286807, PubMed:18799727, PubMed:18347093). Involved in endothelial cell proliferation, tube formation and migration indicative for a role in angiogenesis; the role in neovascularization seems to implicate suppression of SEMA5B (PubMed:24023716). Can negatively regulate androgen receptor signaling (PubMed:18640093). {ECO:0000250|UniProtKB:P58462, ECO:0000269|PubMed:15286807, ECO:0000269|PubMed:18640093, ECO:0000269|PubMed:18799727, ECO:0000269|PubMed:24023716, ECO:0000269|PubMed:25267198, ECO:0000269|PubMed:26647308, ECO:0000305|PubMed:18347093, ECO:0000305|PubMed:24023716}.
• Disease: DISEASE: Note=A chromosomal aberration involving FOXP1 is found in acute lymphoblastic leukemia. Translocation t(9;3)(p13;p14.1) with PAX5.; DISEASE: Mental retardation with language impairment and autistic features (MRLIAF) [MIM:613670]: A developmental disorder characterized by mild to moderate mental retardation, language impairment, and autistic features. Patients show global delay, delayed walking, severely delayed speech development, and behavioral abnormalities, including irritability, hyperactivity, aggression, and stereotypical rigid behaviors. {ECO:0000269|PubMed:20950788, ECO:0000269|PubMed:26647308}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: MicroRNAs in cancer - Homo sapiens (human);Developmental Biology;Transcriptional regulation of pluripotent stem cells (Consensus)

Recessive Scores

• pRec: 0.326

Intolerance Scores

• loftool: 0.0611
• rvis_EVS: -0.38
• rvis_percentile_EVS: 28.01

Haploinsufficiency Scores

• pHI: 0.573
• hipred: Y
• hipred_score: 0.827
• ghis: 0.544

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.893

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Foxp1
• Phenotype: digestive/alimentary phenotype; immune system phenotype; respiratory system phenotype; embryo phenotype; growth/size/body region 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); muscle phenotype; homeostasis/metabolism phenotype; cellular phenotype

Gene ontology

• Biological process: negative regulation of B cell apoptotic process;regulation of transcription by RNA polymerase II;positive regulation of endothelial cell migration;osteoclast differentiation;response to lipopolysaccharide;regulation of tumor necrosis factor production;somatic stem cell population maintenance;chemokine (C-C motif) ligand 2 secretion;osteoclast development;macrophage activation;monocyte activation;endothelial cell activation;regulation of monocyte differentiation;negative regulation of transcription, DNA-templated;positive regulation of smooth muscle cell proliferation;regulation of interleukin-1 beta secretion;regulation of inflammatory response;negative regulation of androgen receptor signaling pathway;T follicular helper cell differentiation;interleukin-21 secretion;regulation of defense response to bacterium;regulation of macrophage colony-stimulating factor production;regulation of endothelial tube morphogenesis;regulation of interleukin-12 secretion
• Cellular component: nucleus;nucleoplasm
• Molecular function: DNA-binding transcription factor activity, RNA polymerase II-specific;protein binding;identical protein binding;sequence-specific DNA binding;protein self-association;metal ion binding;androgen receptor binding