FOXJ1

Chr 17AD

forkhead box J1

Also known as: CILD43, FKHL13, HFH-4, HFH4

NCBI Gene: 2302ENSG00000129654UniProt: Q92949

This gene encodes a member of the forkhead family of transcription factors. Similar genes in zebrafish and mouse have been shown to regulate the transcription of genes that control the production of motile cilia. The mouse ortholog also functions in the determination of left-right asymmetry. Polymorphisms in this gene are associated with systemic lupus erythematosus and allergic rhinitis.[provided by RefSeq, Sep 2009]

Primary Disease Associations & Inheritance

Ciliary dyskinesia, primary, 43MIM #618699
AD
UniProtAllergic rhinitis
143
ClinVar variants
22
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— FOXJ1
🧬
Gene-Disease Validity (ClinGen)
ciliary dyskinesia, primary, 43 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
22 Pathogenic / Likely Pathogenic· 99 VUS of 143 total submissions

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.
0.28LOEUF
pLI 0.969
Z-score 3.04
OE 0.00 (0.00–0.28)
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.
0.70Z-score
OE missense 0.87 (0.78–0.98)
202 obs / 232.0 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.0.00 (0.00–0.28)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.87 (0.78–0.98)
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.0.87
0≤1.21.6
LoF obs/exp: 0 / 10.8Missense obs/exp: 202 / 232.0Syn Z: 1.07

ClinVar Variant Classifications

143 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic18
Likely Pathogenic4
VUS99
Likely Benign17
Benign4
Conflicting1
18
Pathogenic
4
Likely Pathogenic
99
VUS
17
Likely Benign
4
Benign
1
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
15
0
18
Likely Pathogenic
3
0
1
0
4
VUS
2
92
5
0
99
Likely Benign
0
7
0
10
17
Benign
0
0
3
1
4
Conflicting
—1
Total8992411143

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

View in ClinVar →

Protein Context — Lollipop Plot

FOXJ1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

FOXJ1-related motile ciliopathy with hydrocephalus and randomization of left/right body asymmetry

strong
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 J1; FOXJ1
MIM #602291 · *

Ciliary dyskinesia, primary, 43

MIM #618699

Molecular basis of disorder known

Autosomal dominant
📖
GeneReview available — FOXJ1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Choroid plexus mast cells drive tumor-associated hydrocephalus.
Li Y et al.·Cell
2023
MicroRNA-92a-1-5p increases CDX2 by targeting FOXD1 in bile acids-induced gastric intestinal metaplasia.
Li T et al.·Gut
2019
Congenital heart defects caused by FOXJ1.
Padua MB et al.·Hum Mol Genet
2023
A novel heterozygous variant of FOXJ1 in a Chinese female with primary ciliary dyskinesia and hydrocephalus: A case report and literature review.
Gao S et al.·Mol Genet Genomic Med
2023Review
FOXJ1 promotes bladder cancer cell growth and regulates Warburg effect.
Xian S et al.·Biochem Biophys Res Commun
2018
Significance of the detection of TIM-3 and FOXJ1 in prostate cancer.
Lan Y et al.·J BUON
2017
Genetic Risk Factors in Normal Pressure Hydrocephalus: What We Know and What Is Next.
Piccinin CC et al.·Mov Disord
2025
Role of f-box factor foxj1 in differentiation of ciliated airway epithelial cells.
You Y et al.·Am J Physiol Lung Cell Mol Physiol
2004
Insights into the effects of inhaled drugs on airway epithelium with human airway basal cells.
Ogawa F et al.·Biochem Biophys Res Commun
2025
Differential epithelial and stromal LGR5 expression in ovarian carcinogenesis.
Kim H et al.·Sci Rep
2022
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