protein
Forkhead box protein P1
Gene
FOXP1
Organism
Homo sapiens(9606)
Length
677 aa
Mass
75,317 Da
Forkhead box protein P1 (FOXP1) is a transcriptional regulator that functions primarily as a repressor, though it can also activate transcription of specific targets like FBXL7 (UniProt: Q9H334). It plays diverse roles in developmental and cellular processes including specification of lung epithelium, B-cell development, cardiac muscle proliferation, spinal motor neuron organization, and regulation of dopamine neuron identity through PITX3 regulation.
FOXP1 is widely expressed across tissues and functions in multiple biological contexts: it cooperates with FOXP4 in lung epithelial differentiation, regulates immune cell development including T follicular helper cell differentiation and macrophage functions through CSF1R repression, maintains hair follicle stem cell quiescence, and participates in endothelial cell function and angiogenesis. The protein acts as a corepressor with partners like CTBP1 and NCOR2 in various contexts.
FOXP1 mutations are associated with intellectual developmental disorder with language impairment and autistic features (IDDLA, MIM 613670), characterized by global developmental delay, severely delayed speech, and behavioral abnormalities including stereotypical rigid behaviors (UniProt: Q9H334). This gene is classified as SFARI Category 1 with a syndromic autism designation (SFARI Cat 1), indicating strong evidence for involvement in autism spectrum disorder, particularly in syndromic presentations.
Generated from the curated entity record below. May contain errors — verify against source links.
Genetic Evidence · ASD
High confidence — strong genetic evidence from multiple studies
Source: SFARI Gene database · gene.sfari.org
Related Publications
Browse all →Inherited and De Novo Genetic Risk for Autism Impacts Shared Networks.
Ruzzo Elizabeth K et al.Cell2019PMID 31398340Inherited and multiple de novo mutations in autism/developmental delay risk genes suggest a multifactorial model.
Guo Hui et al.Molecular autism2018PMID 30564305Whole genome sequencing resource identifies 18 new candidate genes for autism spectrum disorder.
C Yuen Ryan K et al.Nature neuroscience2017PMID 28263302Identification of common genetic risk variants for autism spectrum disorder.
Grove Jakob et al.Nature genetics2019PMID 30804558Synaptic, transcriptional and chromatin genes disrupted in autism.
De Rubeis Silvia et al.Nature2014PMID 25363760
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 cord 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:18347093, PubMed:18799727). 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). Acts as a transcriptional activator of the FBXL7 promoter; this activity is regulated by AURKA (PubMed:28218735)
Involved in transcriptional regulation in embryonic stem cells (ESCs). Stimulates expression of transcription factors that are required for pluripotency and decreases expression of differentiation-associated genes. Has distinct DNA-binding specifities as compared to the canonical form and preferentially binds DNA with the sequence 5'-CGATACAA-3' (or closely related sequences) (PubMed:21924763). Promotes ESC self-renewal and pluripotency (By similarity)
Disease associations
Intellectual developmental disorder with language impairment and with or without autistic featuresIDDLA
A developmental disorder characterized by mild to moderate intellectual disability, language impairment, and autistic features in some patients. Patients show global delay, delayed walking, severely delayed speech development, and behavioral abnormalities, including irritability, hyperactivity, aggression, and stereotypical rigid behaviors.
Sources
Last updated 5/6/2026, 5:25:36 AM