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GeneE
27 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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S100A4
S100 calcium binding protein A4
Chromosome 1 · 1q21.3
NCBI Gene: 6275Ensembl: ENSG00000196154.13HGNC: HGNC:10494UniProt: P26447
407PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Highly Studied
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
RNA bindingpositive regulation of canonical NF-kappaB signal transductionGO:0005615nucleusAlzheimer diseaseParkinson diseaseneurodegenerative diseasemultiple sclerosis
✦AI Summary

S100A4 is a calcium-binding protein that plays critical roles in cancer progression, metastasis, and cellular signaling. The protein promotes tumor cell invasion and metastasis through multiple mechanisms, including activation of STAT3 signaling pathways 1. S100A4 can be secreted in exosomes from highly metastatic cancer cells, where it enhances metastatic potential by inducing osteopontin expression via STAT3 phosphorylation 1. In tumor-associated macrophages, S100A4 controls protumor polarization by regulating PPAR-γ-dependent fatty acid oxidation, facilitating cancer progression 2. The protein also modulates the tumor microenvironment, with S100A4-positive cancer-associated fibroblasts changing composition during breast cancer progression and correlating with disease outcome 3. Beyond cancer, S100A4 contributes to fibrotic diseases, where anti-S100A4 monoclonal antibody treatment effectively reduces skin fibrosis by targeting inflammatory and fibrotic pathways 4. S100A4 is expressed in various cell types including mast cells, where it regulates cell growth, apoptosis, and matrix metalloproteinase production 5, and in dental odontoblasts as a cellular marker 6. The protein's diverse functions make it a potential therapeutic target and prognostic marker across multiple diseases.

Sources cited
1
S100A4 is secreted in exosomes and promotes metastasis by activating STAT3 signaling and inducing osteopontin expression
PMID: 34035222
2
S100A4 controls protumor macrophage polarization through PPAR-γ-dependent fatty acid oxidation
PMID: 34145030
3
S100A4-positive cancer-associated fibroblasts change composition during breast cancer progression and correlate with disease outcome
PMID: 35122040
4
Anti-S100A4 monoclonal antibody treatment effectively reduces skin fibrosis by targeting inflammatory and fibrotic pathways
PMID: 38108109
5
S100A4 is expressed in mast cells where it regulates cell growth, apoptosis, and matrix metalloproteinase production
PMID: 30097176
6
S100A4 is expressed in dental odontoblasts and odontoblast-like cells as a cellular marker
PMID: 36327571
Disease Associationsⓘ20
Alzheimer diseaseOpen Targets
0.36Weak
Parkinson diseaseOpen Targets
0.36Weak
neurodegenerative diseaseOpen Targets
0.36Weak
multiple sclerosisOpen Targets
0.35Weak
lysosomal storage diseaseOpen Targets
0.35Weak
prostate cancerOpen Targets
0.13Weak
neoplasmOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
non-small cell lung carcinomaOpen Targets
0.11Weak
colorectal carcinomaOpen Targets
0.11Weak
lung cancerOpen Targets
0.11Weak
Familial prostate cancerOpen Targets
0.11Weak
gastric cancerOpen Targets
0.11Weak
acute myeloid leukemiaOpen Targets
0.11Weak
triple-negative breast cancerOpen Targets
0.11Weak
breast cancerOpen Targets
0.11Weak
cancerOpen Targets
0.10Suggestive
pachyonychia congenitaOpen Targets
0.09Suggestive
glioblastoma multiformeOpen Targets
0.09Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
TP53Protein interaction100%MYH9Protein interaction100%ANXA1Protein interaction100%EGFProtein interaction97%SMAD3Protein interaction96%SDF4Protein interaction94%
Tissue Expression6 tissues
Lung
100%
Bone Marrow
20%
Heart
13%
Ovary
3%
Liver
2%
Brain
1%
Gene Interaction Network
Click a node to explore
S100A4TP53MYH9ANXA1EGFSMAD3SDF4
PROTEIN STRUCTURE
Preparing viewer…
PDB4CFQ · 1.37 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.13LoF Tolerant
pLIⓘ
0.16Tolerant
Observed/Expected LoF0.49 [0.24–1.13]
RankingsWhere S100A4 stands among ~20K protein-coding genes
  • #712of 20,598
    Most Researched407 · top 5%
  • #11,677of 17,882
    Most Constrained (LOEUF)1.13
Genes detectedS100A4
Sources retrieved27 papers
Response time—
📄 Sources
27▼
1
S100A4 enhances protumor macrophage polarization by control of PPAR-γ-dependent induction of fatty acid oxidation.
PMID: 34145030
J Immunother Cancer · 2021
1.00
2
ANXA9 facilitates S100A4 and promotes breast cancer progression through modulating STAT3 pathway.
PMID: 38609357
Cell Death Dis · 2024
0.90
3
Clinicopathological and prognostic significance of S100A4 overexpression in colorectal cancer: a meta-analysis.
PMID: 24188373
Diagn Pathol · 2013
0.84
4
Cancer-associated fibroblast compositions change with breast cancer progression linking the ratio of S100A4
PMID: 35122040
Nat Cancer · 2020
0.80
5
Macrophage transition to a myofibroblast state drives fibrotic disease in uropathogenic E. coli-induced epididymo-orchitis.
PMID: 41031892
J Clin Invest · 2025
0.72