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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 15 days ago
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FOSL2
FOS like 2, AP-1 transcription factor subunit
Chromosome 2 Β· 2p23.2
NCBI Gene: 2355Ensembl: ENSG00000075426.13HGNC: HGNC:3798UniProt: P15408
104PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
RNA polymerase II transcription regulatory region sequence-specific DNA bindingpositive regulation of transcription by RNA polymerase IInucleoplasmtranscription factor AP-1 complexaplasia cutis-enamel dysplasia syndromehair colorhypertensionallergic rhinitis
✦AI Summary

FOSL2 is a transcription factor subunit of the AP-1 complex that regulates diverse cellular processes across multiple pathological contexts. As a component of AP-1, FOSL2 functions as a sequence-specific DNA-binding transcription activator 1. In immune contexts, FOSL2 serves as a key determinant of Th17 cell plasticity within the global transcriptional regulatory network governing Th17 differentiation 1. In cancer biology, FOSL2 demonstrates multifaceted roles: it activates Wnt5a transcription in breast cancer-associated fibroblasts to promote VEGF-independent angiogenesis 2, regulates EFNA1 through super-enhancer-driven mechanisms to fuel cervical cancer progression via the Src/AKT/STAT3 pathway 3, and participates in glioblastoma evolution by coordinating tumor-macrophage interactions through the HIF1A-FOSL2 and FOSL2-ANXA1-FPR1/3 axes 4. In cisplatin-resistant non-small cell lung cancer, FOSL2 activates NAMPT expression to suppress ferroptosis 5. FOSL2 expression is also dysregulated in osteoarthritis cartilage, where it represents a therapeutic target mediating abnormal gene expression 6. Additionally, FOSL2 exhibits differential chr2 accessibility in monocyte-derived versus tissue-resident alveolar macrophages in idiopathic pulmonary fibrosis 7, and EP300-mediated acetylation of FOSL2 accelerates cervical cancer proliferation 8. These findings establish FOSL2 as a context-dependent transcriptional regulator with significant implications for cancer progression, inflammatory diseases, and fibrotic pathologies.

Sources cited
1
FOSL2 is activated in glioblastoma evolution and participates in the HIF1A-FOSL2 axis and FOSL2-ANXA1-FPR1/3 axis regulating tumor-macrophage interactions
PMID: 36122307
2
FOSL2 in breast cancer-associated fibroblasts transcriptionally activates Wnt5a to promote VEGF-independent angiogenesis
PMID: 33754039
3
FOSL2 is a transcription factor in super-enhancer regions driving EFNA1 expression in cervical cancer via the Src/AKT/STAT3 pathway
PMID: 39964764
4
FOSL2 is a key determinant of Th17 cell plasticity in the transcriptional regulatory network governing Th17 differentiation
PMID: 23021777
5
FOSL2 shows stronger association with open chromatin in monocyte-derived alveolar macrophages compared to tissue-resident macrophages in idiopathic pulmonary fibrosis
PMID: 38937806
6
EP300-mediated acetylation of FOSL2-K222 accelerates cervical cancer cell proliferation
PMID: 39578447
7
FOSL2 activates NAMPT expression to promote cisplatin resistance in non-small cell lung cancer by inhibiting ferroptosis
PMID: 37370246
8
FOSL2 is dysregulated in osteoarthritis cartilage and represents a therapeutic target mediating abnormal gene expression
PMID: 30081074
Disease Associationsβ“˜21
aplasia cutis-enamel dysplasia syndromeOpen Targets
0.69Moderate
hair colorOpen Targets
0.50Moderate
hypertensionOpen Targets
0.48Moderate
allergic rhinitisOpen Targets
0.48Moderate
Crohn's diseaseOpen Targets
0.47Moderate
inflammatory bowel diseaseOpen Targets
0.45Moderate
rosaceaOpen Targets
0.43Moderate
atopic eczemaOpen Targets
0.43Moderate
neurodegenerative diseaseOpen Targets
0.41Moderate
Eczematoid dermatitisOpen Targets
0.41Moderate
Increased blood pressureOpen Targets
0.37Weak
deep vein thrombosisOpen Targets
0.34Weak
psoriasisOpen Targets
0.34Weak
ulcerative colitisOpen Targets
0.33Weak
ankylosing spondylitisOpen Targets
0.33Weak
sclerosing cholangitisOpen Targets
0.33Weak
allergic diseaseOpen Targets
0.32Weak
allergic conjunctivitisOpen Targets
0.32Weak
Genu valgumOpen Targets
0.28Weak
Genu varumOpen Targets
0.27Weak
Aplasia cutis-enamel dysplasiaUniProt
Pathogenic Variants6
NM_005253.4(FOSL2):c.619C>T (p.Gln207Ter)Likely pathogenic
Aplasia cutis-enamel dysplasia syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 207
NM_005253.4(FOSL2):c.810_811del (p.Pro271fs)Likely pathogenic
Neurodevelopmental disorder
β˜…β˜†β˜†β˜†2021β†’ Residue 271
NM_005253.4(FOSL2):c.595C>T (p.Arg199Ter)Pathogenic
Aplasia cutis-enamel dysplasia syndrome
β˜†β˜†β˜†β˜†2024β†’ Residue 199
NM_005253.4(FOSL2):c.662_663del (p.Val221fs)Pathogenic
Aplasia cutis-enamel dysplasia syndrome
β˜†β˜†β˜†β˜†2024β†’ Residue 221
NM_005253.4(FOSL2):c.605del (p.Pro202fs)Pathogenic
Aplasia cutis-enamel dysplasia syndrome
β˜†β˜†β˜†β˜†2024β†’ Residue 202
NM_005253.4(FOSL2):c.579_589del (p.Ser194fs)Pathogenic
Aplasia cutis-enamel dysplasia syndrome
β˜†β˜†β˜†β˜†2024β†’ Residue 194
View on ClinVar β†—
Related Genes
MAPK9Protein interaction94%CEBPBProtein interaction93%MAPK12Protein interaction92%MAPK8Protein interaction91%TRIB1Protein interaction89%MAPK14Protein interaction86%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
98%
Lung
88%
Brain
27%
Liver
15%
Heart
14%
Gene Interaction Network
Click a node to explore
FOSL2MAPK9CEBPBMAPK12MAPK8TRIB1MAPK14
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt P15408
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.28Highly Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.09 [0.04–0.28]
RankingsWhere FOSL2 stands among ~20K protein-coding genes
  • #4,585of 20,598
    Most Researched104 Β· top quartile
  • #3,340of 5,498
    Most Pathogenic Variants6
  • #982of 17,882
    Most Constrained (LOEUF)0.28 Β· top 10%
Genes detectedFOSL2
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Natural Coevolution of Tumor and Immunoenvironment in Glioblastoma.
PMID: 36122307
Cancer Discov Β· 2022
1.00
2
FOSL2 promotes VEGF-independent angiogenesis by transcriptionnally activating Wnt5a in breast cancer-associated fibroblasts.
PMID: 33754039
Theranostics Β· 2021
0.90
3
Super-enhancer-driven EFNA1 fuels tumor progression in cervical cancer via the FOSL2-Src/AKT/STAT3 axis.
PMID: 39964764
J Clin Invest Β· 2025
0.80
4
A validated regulatory network for Th17 cell specification.
PMID: 23021777
Cell Β· 2012
0.70
5
Multiomic analysis of monocyte-derived alveolar macrophages in idiopathic pulmonary fibrosis.
PMID: 38937806
J Transl Med Β· 2024
0.60