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GeneE
25 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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FOXP2
forkhead box P2
Chromosome 7 Β· 7q31.1
NCBI Gene: 93986Ensembl: ENSG00000128573.28HGNC: HGNC:13875UniProt: B7ZLK5
184PubMed Papers
21Diseases
0Drugs
60Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
RESEARCH IMPACT
TrendingVariant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
nucleoplasmDNA bindingcerebral cortex developmentputamen developmentchildhood apraxia of speechattention deficit hyperactivity disordergenetic disorderosteoarthritis
✦AI Summary

FOXP2 is a transcriptional repressor and DNA-binding transcription factor that plays pleiotropic roles in development and neural function. Structurally, FOXP2 contains a forkhead box DNA-binding domain and glutamine-rich regions; its DNA binding provides a solubilizing effect that prevents pathological protein aggregation 1. The gene is primarily known for its role in speech and language development, being the first gene implicated in a speech-language disorder 2. In the brain, human FOXP2 increases synaptic plasticity and dendrite connectivity in the basal ganglia, which regulate language, cognition, and motor control 3. FOXP2 shows human-specific upregulation in specific neuronal subtypes of the posterior cingulate cortex 4, and is implicated in thalamic development where its overexpression mediates axon overgrowth in a 22q11.2 microdeletion model of psychiatric disorders 5. Beyond neurological functions, FOXP2 plays developmental roles in cardiac tissue, where it is implicated in the pacemaker phenotype 6. Recently, FOXP2 was identified as a promoter of kidney fibrosis through epithelial-to-mesenchymal transition and cell cycle arrest in tubular cells 7. Mutations in FOXP2 are associated with congenital disorders, highlighting its importance in human development 8.

Sources cited
1
DNA binding protects FOXP2 from pathological protein aggregation; human-specific amino acid substitutions in the EVO patch affect solubility
PMID: 40239647
2
FOXP2 is the first gene implicated in speech-language disorder and involved in molecular mechanisms of human speech
PMID: 24765219
3
Human FOXP2 increases synaptic plasticity and dendrite connectivity in basal ganglia, regulating language, cognition, and motor control
PMID: 19490887
4
Human-specific upregulation of FOXP2 occurs in select neuronal subtypes in posterior cingulate cortex
PMID: 37468639
5
FOXP2 overexpression mediates thalamic axon overgrowth in 22q11.2 deletion models associated with psychiatric disorders
PMID: 38382530
6
FOXP2 is implicated in the cardiac pacemaker phenotype
PMID: 37438528
7
FOXP2 overexpression promotes kidney fibrosis through epithelial-to-mesenchymal transition and G2/M cell cycle arrest
PMID: 39656554
8
FOXP2 mutations are associated with human congenital disorders
PMID: 15492844
Disease Associationsβ“˜21
childhood apraxia of speechOpen Targets
0.78Strong
attention deficit hyperactivity disorderOpen Targets
0.54Moderate
genetic disorderOpen Targets
0.53Moderate
osteoarthritisOpen Targets
0.51Moderate
substance-related disorderOpen Targets
0.49Moderate
PainOpen Targets
0.48Moderate
risk-taking behaviourOpen Targets
0.48Moderate
post-traumatic stress disorderOpen Targets
0.47Moderate
insomniaOpen Targets
0.47Moderate
Neck painOpen Targets
0.46Moderate
cannabis dependenceOpen Targets
0.46Moderate
major depressive disorderOpen Targets
0.46Moderate
IrritabilityOpen Targets
0.45Moderate
Limb painOpen Targets
0.45Moderate
Back painOpen Targets
0.45Moderate
Abdominal painOpen Targets
0.44Moderate
tooth diseaseOpen Targets
0.44Moderate
spondylosisOpen Targets
0.44Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
Shoulder painOpen Targets
0.41Moderate
Speech-language disorder 1UniProt
Pathogenic Variants60
NM_014491.4(FOXP2):c.1432C>T (p.Arg478Ter)Pathogenic
Childhood apraxia of speech|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 478
NM_014491.4(FOXP2):c.1426C>T (p.Arg476Ter)Pathogenic
Childhood apraxia of speech|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 476
NM_014491.4(FOXP2):c.982C>T (p.Arg328Ter)Pathogenic
Childhood apraxia of speech|not provided|See cases|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 328
NM_014491.4(FOXP2):c.559C>T (p.Gln187Ter)Pathogenic
Childhood apraxia of speech|Inborn genetic diseases
β˜…β˜…β˜†β˜†2025β†’ Residue 187
NM_014491.4(FOXP2):c.1126C>T (p.Arg376Ter)Pathogenic
Childhood apraxia of speech|not provided
β˜…β˜…β˜†β˜†2025β†’ Residue 376
NM_014491.4(FOXP2):c.502C>T (p.Gln168Ter)Pathogenic
not provided|Inborn genetic diseases
β˜…β˜…β˜†β˜†2023β†’ Residue 168
NM_014491.4(FOXP2):c.1690C>T (p.Arg564Ter)Pathogenic
Childhood apraxia of speech|not provided
β˜…β˜…β˜†β˜†2023β†’ Residue 564
NM_014491.4(FOXP2):c.1658G>A (p.Arg553His)Pathogenic
Childhood apraxia of speech|FOXP2-related disorder
β˜…β˜…β˜†β˜†2022β†’ Residue 553
NM_014491.4(FOXP2):c.1371del (p.Thr458fs)Pathogenic
not provided
β˜…β˜…β˜†β˜†2019β†’ Residue 458
NM_014491.4(FOXP2):c.307C>T (p.Gln103Ter)Pathogenic
Childhood apraxia of speech
β˜…β˜†β˜†β˜†2026β†’ Residue 103
NM_014491.4(FOXP2):c.1437_1444del (p.His479fs)Likely pathogenic
Childhood apraxia of speech
β˜…β˜†β˜†β˜†2025β†’ Residue 479
NM_014491.4(FOXP2):c.1644G>A (p.Trp548Ter)Likely pathogenic
Childhood apraxia of speech
β˜…β˜†β˜†β˜†2025β†’ Residue 548
NM_014491.4(FOXP2):c.1684_1694del (p.Phe562fs)Pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2025β†’ Residue 562
NM_014491.4(FOXP2):c.737del (p.Pro246fs)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 246
NM_014491.4(FOXP2):c.1621T>G (p.Phe541Val)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 541
NM_014491.4(FOXP2):c.1793del (p.Ile598fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 598
NM_014491.4(FOXP2):c.637C>T (p.Gln213Ter)Likely pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 213
NM_014491.4(FOXP2):c.1747C>T (p.Arg583Ter)Likely pathogenic
Childhood apraxia of speech
β˜…β˜†β˜†β˜†2025β†’ Residue 583
NM_014491.4(FOXP2):c.1526A>G (p.Tyr509Cys)Likely pathogenic
Inborn genetic diseases
β˜…β˜†β˜†β˜†2024β†’ Residue 509
NM_014491.4(FOXP2):c.3G>T (p.Met1Ile)Pathogenic
not provided
β˜…β˜†β˜†β˜†2024β†’ Residue 1
View on ClinVar β†—
Related Genes
CNTNAP2Protein interaction98%FOXP1Protein interaction95%FOXP4Protein interaction95%CTBP1Protein interaction93%NFATC2Protein interaction84%FOXP3Protein interaction81%
Tissue Expression6 tissues
Ovary
100%
Liver
53%
Brain
38%
Heart
30%
Lung
19%
Bone Marrow
0%
Gene Interaction Network
Click a node to explore
FOXP2CNTNAP2FOXP1FOXP4CTBP1NFATC2FOXP3
PROTEIN STRUCTURE
Preparing viewer…
PDB2A07 Β· 1.90 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.16Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.09 [0.06–0.16]
RankingsWhere FOXP2 stands among ~20K protein-coding genes
  • #2,346of 20,598
    Most Researched184 Β· top quartile
  • #1,163of 5,498
    Most Pathogenic Variants60 Β· top quartile
  • #235of 17,882
    Most Constrained (LOEUF)0.16 Β· top 5%
Genes detectedFOXP2
Sources retrieved25 papers
Response timeβ€”
πŸ“„ Sources
25β–Ό
1
Spatially resolved multiomics of human cardiac niches.
PMID: 37438528
Nature Β· 2023
1.00
2
Human FOX gene family (Review).
PMID: 15492844
Int J Oncol Β· 2004
0.90
3
The untold stories of the speech gene, the
PMID: 29725501
Genes Cancer Β· 2018
0.84
4
FOXP2.
PMID: 24765219
Wiley Interdiscip Rev Cogn Sci Β· 2013
0.80
5
Thalamocortical organoids enable inΒ vitro modeling of 22q11.2 microdeletion associated with neuropsychiatric disorders.
PMID: 38382530
Cell Stem Cell Β· 2024
0.70