FOXP1

Chr 3AD

forkhead box P1

Also known as: 12CC4, HSPC215, MFH, QRF1, hFKH1B

NCBI Gene: 27086ENSG00000114861UniProt: Q9H334

This gene belongs to subfamily P of the forkhead box (FOX) transcription factor family. Forkhead box transcription factors play important roles in the regulation of tissue- and cell type-specific gene transcription during both development and adulthood. Forkhead box P1 protein contains both DNA-binding- and protein-protein binding-domains. This gene may act as a tumor suppressor as it is lost in several tumor types and maps to a chromosomal region (3p14.1) reported to contain a tumor suppressor gene(s). Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Intellectual developmental disorder with language impairment with or without autistic featuresMIM #613670
AD
577
ClinVar variants
67
Pathogenic / LP
1.00
pLI score· haploinsufficient
2
Active trials
Clinical Summary— FOXP1
🧬
Gene-Disease Validity (ClinGen)
intellectual disability-severe speech delay-mild dysmorphism syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

2 total gene-disease associations curated

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
67 Pathogenic / Likely Pathogenic· 223 VUS of 577 total submissions
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.17LOEUF
pLI 1.000
Z-score 5.75
OE 0.07 (0.03–0.17)
Highly constrained

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

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.28Z-score
OE missense 0.67 (0.60–0.74)
247 obs / 370.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.17)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.60–0.74)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.18
0≤1.21.6
LoF obs/exp: 3 / 44.3Missense obs/exp: 247 / 370.2Syn Z: -1.69

ClinVar Variant Classifications

577 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic24
VUS223
Likely Benign260
Benign15
Conflicting12
43
Pathogenic
24
Likely Pathogenic
223
VUS
260
Likely Benign
15
Benign
12
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
19
1
23
0
43
Likely Pathogenic
13
6
5
0
24
VUS
5
176
40
2
223
Likely Benign
1
27
97
135
260
Benign
0
4
6
5
15
Conflicting
—12
Total38214171142577

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

FOXP1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FOXP1-related intellectual developmental disorder with language impairment and autistic features

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
FORKHEAD BOX P1; FOXP1
MIM #605515 · *

Intellectual developmental disorder with language impairment with or without autistic features

MIM #613670

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — FOXP1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Integrative genomic profiling of human prostate cancer.
Taylor BS et al.·Cancer Cell
2010
NAT10/ac4C/FOXP1 Promotes Malignant Progression and Facilitates Immunosuppression by Reprogramming Glycolytic Metabolism in Cervical Cancer.
Chen X et al.·Adv Sci (Weinh)
2023
Mutations of the Transcriptional Corepressor ZMYM2 Cause Syndromic Urinary Tract Malformations.
Connaughton DM et al.·Am J Hum Genet
2020
Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray.
Hans CP et al.·Blood
2004
Follicular lymphoma comprises germinal center-like and memory-like molecular subtypes with prognostic significance.
Laurent C et al.·Blood
2024
Genomic and transcriptomic analysis of breast cancer identifies novel signatures associated with response to neoadjuvant chemotherapy.
Yin G et al.·Genome Med
2024
Solving the Etiology of Developmental and Epileptic Encephalopathy with Spike-Wave Activation in Sleep (D/EE-SWAS).
Viswanathan S et al.·Ann Neurol
2024
Meta-analysis of GWAS of over 16,000 individuals with autism spectrum disorder highlights a novel locus at 10q24.32 and a significant overlap with schizophrenia.
Autism Spectrum Disorders Working Group of The Psychiatric Genomics Consortium·Mol Autism
2017Meta-analysis
Ectopic expression of GDF15 in cancer-associated fibroblasts enhances melanoma immunosuppression via the GFRAL/RET cascade.
Zhao Z et al.·J Immunother Cancer
2025
Multiple sclerosis patient-derived spontaneous B cells have distinct EBV and host gene expression profiles in active disease.
Soldan SS et al.·Nat Microbiol
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Intragenic loss-of-function variants in transcription factors MAZ, FOXP1 and SIN3B in colobomatous microphthalmia.
Seese SE et al.·J Med Genet
2026
Identification of novel FOXP1 variants in four unrelated patients with intellectual disability and speech impairment.
Xiang J et al.·Front Neurol
2026🔓 Open AccessCohort
Cortex-Restricted Deletion of Foxp1 Impairs Visual Responses by Disrupting Geniculocortical Connections in a Mouse Model of Autism.
Li X et al.·Invest Ophthalmol Vis Sci
2026🔓 Open AccessFunctional
The dynamic nature of genetic risk for schizophrenia within genes regulated by FOXP1 during neurodevelopment.
Ali D et al.·Hum Mol Genet
2026
Luteolin Enhances Endothelial Barrier Function and Attenuates Myocardial Ischemia-Reperfusion Injury via FOXP1-NLRP3 Pathway.
Xie H et al.·Int J Mol Sci
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
16P11.2 Deletion Syndrome16p11.2 Duplications1Q21.1 Deletion

Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight

RECRUITING
NCT01238250Simons SearchlightStarted 2010-10
FOXP1Mental Retardation With Language Impairment and With or Without Autistic FeaturesAutism Spectrum Disorder

FOXP1 Syndrome: The Seaver Autism Center for Research and Treatment is Characterizing FOXP1-related Neurodevelopmental Disorders Using Genetic, Medical, and Neuropsychological Measures.

RECRUITING
NCT03718923Icahn School of Medicine at Mount SinaiStarted 2016-03-28

External Resources

Links to major genomics databases and tools