FOSL1

Chr 11

FOS like 1, AP-1 transcription factor subunit

Also known as: FRA, FRA1, fra-1

NCBI Gene: 8061ENSG00000175592UniProt: P15407

The Fos gene family consists of 4 members: FOS, FOSB, FOSL1, and FOSL2. These genes encode leucine zipper proteins that can dimerize with proteins of the JUN family, thereby forming the transcription factor complex AP-1. As such, the FOS proteins have been implicated as regulators of cell proliferation, differentiation, and transformation. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2014]

63
ClinVar variants
10
Pathogenic / LP
0.16
pLI score
0
Active trials
Clinical Summary— FOSL1
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.29) despite low pLI — interpret in context.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 50 VUS of 63 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.75LOEUF
pLI 0.158
Z-score 2.12
OE 0.29 (0.13–0.75)
Tolerant

Typical tolerance to LoF variation

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.
0.40Z-score
OE missense 0.91 (0.79–1.05)
142 obs / 155.9 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.0.29 (0.13–0.75)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.91 (0.79–1.05)
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.0.83
0≤1.21.6
LoF obs/exp: 3 / 10.4Missense obs/exp: 142 / 155.9Syn Z: 1.01

ClinVar Variant Classifications

63 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic8
Likely Pathogenic2
VUS50
Benign3
8
Pathogenic
2
Likely Pathogenic
50
VUS
3
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
8
0
8
Likely Pathogenic
0
0
2
0
2
VUS
0
46
4
0
50
Likely Benign
0
0
0
0
0
Benign
0
1
0
2
3
Total04714263

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

View in ClinVar →

Protein Context — Lollipop Plot

FOSL1 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Spatiotemporal single-cell roadmap of human skin wound healing.
Liu Z et al.·Cell Stem Cell
2025
Lgr4 Governs a Pro-Inflammatory Program in Macrophages to Antagonize Post-Infarction Cardiac Repair.
Huang CK et al.·Circ Res
2020
Trends in Research of Odontogenic Keratocyst and Ameloblastoma.
Liu XH et al.·J Dent Res
2025Review
CYTOR Facilitates Formation of FOSL1 Phase Separation and Super Enhancers to Drive Metastasis of Tumor Budding Cells in Head and Neck Squamous Cell Carcinoma.
Wang W et al.·Adv Sci (Weinh)
2024
FOSL1: The core regulatory hub of tumor-neural interactions and its clinical translational prospects.
Pu N et al.·Int Immunopharmacol
2025Review
The dual role of POSTN in maintaining glioblastoma stem cells and the immunosuppressive phenotype of microglia in glioblastoma.
Wang H et al.·J Exp Clin Cancer Res
2024
CLIP170 enhancing FOSL1 expression via attenuating ubiquitin-mediated degradation of β-catenin drives renal cell carcinoma progression.
Huang Y et al.·Cell Mol Life Sci
2024
FOSL1 promotes stem cell‑like characteristics and anoikis resistance to facilitate tumorigenesis and metastasis in osteosarcoma by targeting SOX2.
Wang Y et al.·Int J Mol Med
2024
Noncoding RNAs as regulators of FOSL1 in cancer.
Wang X et al.·Front Immunol
2025Review
FOSL1's Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review.
Khedri A et al.·Int J Mol Sci
2024Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
PKM2 Lactylation Promotes Colorectal Cancer Vasculogenic Mimicry and Bevacizumab Resistance by Facilitating FOSL1 Super-Enhancer Formation.
Li W et al.·Cancer Res
2026
Mesenchymal stem cells-derived TGF-β1 promotes polarization of M2 macrophages in mice with acute-on-chronic liver failure via FOSL1/MERTK axis.
Chen JF et al.·Stem Cell Res Ther
2026
FOSL1 promotes homologous recombination repair and camptothecin resistance via TCOF1-mediated ribosome biogenesis in non-small cell lung cancer.
Hao C et al.·Transl Oncol
2026🔓 Open Access
FOSL1 Orchestrates Epigenetic Reprogramming of Anaplastic Thyroid Cancer and Suppresses Natural Killer Cell-Mediated Antitumor Immunity.
Huo Y et al.·Cancer Res
2026
Targeting the FOSL1/IKKα positive feedback loop attenuates glioblastoma malignancy via suppression of NF-κB signaling.
Zhang B et al.·Theranostics
2026🔓 Open Access
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