FOXP2

Chr 7

forkhead box P2

Also known as: CAGH44, SPCH1, TNRC10

NCBI Gene: 93986ENSG00000128573UniProt: O15409

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]

GeneReviewsResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSpeech-language disorder 1

Clinical highlights

Gene-disease validity (ClinGen)
specific language disorder · ADDefinitivesufficient evidence for diagnostic panels
Interpreting a novel variant
Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.
1
Active trials
101
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.22
LOEUF· LoF intol.
LOF
Mechanism· G2P
📖
GeneReview available — FOXP2
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?
0.22LOEUF
pLI 1.000
Z-score 6.06
OE 0.11 (0.06–0.22)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?
1.90Z-score
OE missense 0.73 (0.66–0.80)
276 obs / 380.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?
LoF OE?0.11 (0.06–0.22)
0≤0.351.4
Missense OE?0.73 (0.66–0.80)
0≤0.61.4
Synonymous OE?1.11
0≤1.21.6
LoF obs/exp: 6 / 54.1Missense obs/exp: 276 / 380.0Syn Z: -0.99

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

FOXP2 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients