FOXP4

Chr 6

forkhead box P4

Also known as: hFKHLA

NCBI Gene: 116113ENSG00000137166UniProt: Q8IVH2

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. Many members of the forkhead box gene family, including members of subfamily P, have roles in mammalian oncogenesis. This gene may play a role in the development of tumors of the kidney and larynx. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. [provided by RefSeq, Jul 2008]

150
ClinVar variants
10
Pathogenic / LP
0.98
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FOXP4
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 125 VUS of 150 total submissions
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?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.
0.31LOEUF
pLI 0.982
Z-score 4.64
OE 0.15 (0.07–0.31)
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.
1.95Z-score
OE missense 0.73 (0.67–0.80)
304 obs / 415.7 exp
Tolerant

Mild missense constraint

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.0.15 (0.07–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.67–0.80)
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.1.06
0≤1.21.6
LoF obs/exp: 5 / 34.4Missense obs/exp: 304 / 415.7Syn Z: -0.65

ClinVar Variant Classifications

150 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS125
Likely Benign10
Benign5
8
Pathogenic
2
Likely Pathogenic
125
VUS
10
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
7
0
8
Likely Pathogenic
0
1
1
0
2
VUS
9
105
10
1
125
Likely Benign
0
5
1
4
10
Benign
0
1
0
4
5
Total9113199150

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXP4 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FOXP4-related developmental disorder

moderate
ADUndeterminedAltered Gene Product Structure
Dev. Disorders
G2P ↗
missense variantstop gained NMD escapingframeshift variant NMD triggering

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
The clinical prognostic value of lncRNA FOXP4-AS1 in cancer patients: A meta-analysis and bioinformatics analysis based on TCGA datasets.
Shu Q et al.·Medicine (Baltimore)
2022Meta-analysis
Patients-Derived Organoids Sequencing-based FOXP4 Facilitates Radioresistance by Transcriptionally Modifying GPX4 to Regulate ferroptosis in Colorectal Cancer.
Chen Q et al.·Adv Sci (Weinh)
2025Cohort
Cis-Regulatory Alterations in FOXP4 Modulate Esophageal Cancer Susceptibility Induced by Chronic Alcohol Exposure.
Niu S et al.·Cancer Res
2025
FOXP4 Variants Are Associated With Plateau Iris and Angle Closure Glaucoma.
Presley W et al.·Invest Ophthalmol Vis Sci
2025
FOXP4-mediated induction of PTK7 activates the Wnt/β-catenin pathway and promotes ovarian cancer development.
Ji J et al.·Cell Death Dis
2024
Long Noncoding RNA FOXP4-AS1 Predicts Unfavourable Prognosis and Regulates Proliferation and Invasion in Hepatocellular Carcinoma.
Liang J et al.·Biomed Res Int
2021
Androgen-responsive FOXP4 is a target for endometrial carcinoma.
Kayahashi K et al.·Commun Biol
2024
Recurrent FOXP4 nonsense variant in two unrelated patients: Association with neurodevelopmental disease and congenital diaphragmatic hernia.
Del Viso F et al.·Am J Med Genet A
2023Case report
[Genetic factors associated with long COVID].
Gamero-de-Luna EJ et al.·Semergen
2024
Polymorphisms of IFN signaling genes and FOXP4 influence the severity of COVID-19.
Zhang F et al.·BMC Infect Dis
2024
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools