FOXP2

Protein identityUniProt · HPA

UniProt accession

O15409

Gene

FOXP2

Ensembl

ENSG00000128573

Chromosome

7

Canonical length

715 aa

Protein class

Disease related genes, Human disease related genes, Predicted intracellular proteins, Transcription factors

Subcellular location

Nucleoplasm

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the forkhead/winged-helix (FOX) family of transcription factors. It is expressed in fetal and adult brain as well as in several other organs such as the lung and gut. The protein product contains a FOX DNA-binding domain and a large polyglutamine tract and is an evolutionarily conserved transcription factor, which may bind directly to approximately 300 to 400 gene promoters in the human genome to regulate the expression of a variety of genes. This gene is required for proper development of speech and language regions of the brain during embryogenesis, and may be involved in a variety of biological pathways and cascades that may ultimately influence language development. Mutations in this gene cause speech-language disorder 1 (SPCH1), also known as autosomal dominant speech and language disorder with orofacial dyspraxia. Multiple alternative transcripts encoding different isoforms have been identified in this gene.[provided by RefSeq, Feb 2010]

Canonical amino-acid sequenceUniProt

715 residues, UniProt reviewed canonical sequence.

>O15409|FOXP2
     1  MMQESATETI SNSSMNQNGM STLSSQLDAG SRDGRSSGDT SSEVSTVELL HLQQQQALQA
    61  ARQLLLQQQT SGLKSPKSSD KQRPLQVPVS VAMMTPQVIT PQQMQQILQQ QVLSPQQLQA
   121  LLQQQQAVML QQQQLQEFYK KQQEQLHLQL LQQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ
   181  QQQQQQQQQQ QHPGKQAKEQ QQQQQQQQQL AAQQLVFQQQ LLQMQQLQQQ QHLLSLQRQG
   241  LISIPPGQAA LPVQSLPQAG LSPAEIQQLW KEVTGVHSME DNGIKHGGLD LTTNNSSSTT
   301  SSNTSKASPP ITHHSIVNGQ SSVLSARRDS SSHEETGASH TLYGHGVCKW PGCESICEDF
   361  GQFLKHLNNE HALDDRSTAQ CRVQMQVVQQ LEIQLSKERE RLQAMMTHLH MRPSEPKPSP
   421  KPLNLVSSVT MSKNMLETSP QSLPQTPTTP TAPVTPITQG PSVITPASVP NVGAIRRRHS
   481  DKYNIPMSSE IAPNYEFYKN ADVRPPFTYA TLIRQAIMES SDRQLTLNEI YSWFTRTFAY
   541  FRRNAATWKN AVRHNLSLHK CFVRVENVKG AVWTVDEVEY QKRRSQKITG SPTLVKNIPT
   601  SLGYGAALNA SLQAALAESS LPLLSNPGLI NNASSGLLQA VHEDLNGSLD HIDSNGNSSP
   661  GCSPQPHIHS IHVKEEPVIA EDEDCPMSLV TTANHSPELE DDREIEEEPL SEDLE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against FOXP2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.58

Highest tissue expression

17 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about FOXP2.

Disease | AllUniProt

Conditions FOXP2 is implicated in, by any mechanism.

• Speech-language disorder 1 (SPCH1) MIM:602081

Disease | GeneticClinVar

62 pathogenic / likely-pathogenic of 425 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Childhood apraxia of speech
• Inborn genetic diseases
• FOXP2-related disorder
• See cases
• Intellectual disability

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.22

gnomAD pLI

1

gnomAD missense Z

1.9

DepMap mean gene effect

-0.02

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• camera-type eye development
• cerebellar Purkinje cell differentiation
• cerebral cortex development
• epithelial cell proliferation involved in lung morphogenesis
• gene expression
• lung alveolus development
• negative regulation of DNA-templated transcription
• positive regulation of epithelial cell proliferation involved in lung morphogenesis
• positive regulation of mesenchymal cell proliferation
• post-embryonic development
• regulation of transcription by RNA polymerase II
• righting reflex
• skeletal muscle tissue development
• smooth muscle tissue development
• vocal learning
• vocalization behavior
• caudate nucleus development
• putamen development

Molecular functions

• DNA binding
• DNA-binding transcription factor activity
• DNA-binding transcription factor activity, RNA polymerase II-specific
• DNA-binding transcription repressor activity, RNA polymerase II-specific
• identical protein binding
• protein homodimerization activity
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• sequence-specific DNA binding
• transcription coregulator binding
• zinc ion binding

Cellular components

• chromatin
• nucleus

Protein domainsUniProt · Pfam · InterPro

• Fork head domain
• Fork head domain conserved site 2
• FOXP, coiled-coil domain
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Forkhead box protein P1/P2, forkhead domain
• Forkhead box protein P
• Forkhead domain
• FOXP coiled-coil domain

KeywordsUniProt

• Chromosomal rearrangement
• DNA-binding
• Metal-binding
• Nucleus
• Repressor
• Transcription
• Transcription regulation
• Zinc
• Zinc-finger

InteractionsUniProt · HPA

Protein binding partners of FOXP2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• CTBP1
• FOXP1
• ZMYM2
• TBR1
• CTBP2
• FOXP4