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5 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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FOXL3
forkhead box L3
Chromosome 7 · 7p22.3
NCBI Gene: 116033993Ensembl: ENSG00000248767.2HGNC: HGNC:54201UniProt: A0A1W2PRP0
0PubMed Papers
10Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA polymerase II cis-regulatory region sequence-specific DNA bindingDNA-binding transcription factor activity, RNA polymerase II-specificregulation of transcription by RNA polymerase IIanatomical structure morphogenesisovarian dysfunctioncervical carcinomaAbruptio Placentaepreeclampsia
✦AI Summary

FOXL3 (forkhead box L3) is a transcriptional regulator that functions as a germ cell-intrinsic determinant of sexual fate in vertebrates, particularly in teleost fish 1. As a DNA-binding transcription factor specific to RNA polymerase II, FOXL3 plays a critical role in gonadal sex differentiation through evolutionarily conserved mechanisms 2. In testicular development, FOXL3 operates within the AR-foxl3-rec8/fbxo47 signaling axis, where androgens enhance FOXL3 promoter activity, enabling FOXL3 to upregulate meiotic genes rec8 and fbxo47 that facilitate spermatogenesis 3. Expression patterns indicate FOXL3 is predominantly expressed in male germ cells, whereas its paralog FOXL2 specializes in ovarian somatic cells, representing subfunctionalization following gene duplication 2. FOXL3 expression is tightly regulated by miRNA suppression and is sensitive to endocrine disruption; environmental exposure to pharmaceutical mixtures increases FOXL3 mRNA levels approximately 5-fold, affecting germ cell fate determination 4. Loss-of-function studies demonstrate that FOXL3-established germ cell sexual identity enables proper gametogenesis independently of surrounding somatic cell sex 1. This makes FOXL3 essential for the cell-autonomous determination of germline sexual identity distinct from other gametogenic pathways.

Sources cited
1
FOXL3 is a germ cell-intrinsic factor in sperm-egg fate decision; establishes germline sexual identity independently of somatic cells
PMID: 27009043
2
FOXL3 is evolutionarily conserved paralog of FOXL2; predominantly expressed in male germ cells vs. FOXL2 in ovarian somatic cells
PMID: 27441599
3
FOXL3 regulates testis development through AR-foxl3-rec8/fbxo47 axis; androgen upregulates FOXL3 promoter activity
PMID: 32057909
4
FOXL3 expression increased 5-fold in ovary after pharmaceutical mixture exposure; sensitive to endocrine disruption
PMID: 30347285
5
miRNA novel_158 predicted to suppress FOXL3 expression in common carp gonads
PMID: 37998366
Disease Associationsⓘ10
ovarian dysfunctionOpen Targets
0.18Weak
cervical carcinomaOpen Targets
0.09Suggestive
Abruptio PlacentaeOpen Targets
0.07Suggestive
preeclampsiaOpen Targets
0.03Suggestive
iron metabolism diseaseOpen Targets
0.03Suggestive
atrophic gastritisOpen Targets
0.02Suggestive
pyelonephritisOpen Targets
0.02Suggestive
skull disorderOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
infertilityOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FOXD4Shared pathway100%FOXD2Shared pathway100%FOXQ1Shared pathway100%FOXD4L1Shared pathway100%FOXD4L3Shared pathway100%FOXD4L4Shared pathway100%
Tissue Expression6 tissues
Heart
0%
Brain
0%
Ovary
0%
Bone Marrow
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
FOXL3FOXD4FOXD2FOXQ1FOXD4L1FOXD4L3FOXD4L4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt A0A1W2PRP0
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.97LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.84 [1.16–1.97]
RankingsWhere FOXL3 stands among ~20K protein-coding genes
  • #19,485of 20,598
    Most Researched0
  • #17,768of 17,882
    Most Constrained (LOEUF)1.97
Genes detectedFOXL3
Sources retrieved5 papers
Response time—
📄 Sources
5
1
The Mechanism of Germline Sex Determination in Vertebrates.
PMID: 27009043
Biol Reprod · 2016
1.00
2
Foxl2 and Its Relatives Are Evolutionary Conserved Players in Gonadal Sex Differentiation.
PMID: 27441599
Sex Dev · 2016
0.80
3
In vitro effects of androgen on testicular development by the AR-foxl3-rec8/fbxo47 axis in orange-spotted grouper (Epinephelus coioides).
PMID: 32057909
Gen Comp Endocrinol · 2020
0.60
4
Differential Expression of miRNAs, lncRNAs, and circRNAs between Ovaries and Testes in Common Carp (
PMID: 37998366
Cells · 2023
0.40
5
Environmentally-relevant mixture of pharmaceutical drugs stimulates sex-steroid hormone production and modulates the expression of candidate genes in the ovary of juvenile female rainbow trout.
PMID: 30347285
Aquat Toxicol · 2018
0.20