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25 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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SAA1
serum amyloid A1
Chromosome 11 · 11p15.1
NCBI Gene: 6288Ensembl: ENSG00000173432.13HGNC: HGNC:10513UniProt: P0DJI8
304PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
G protein-coupled receptor bindingpositive regulation of cytokine productionpositive regulation of cytosolic calcium ion concentrationpositive regulation of cell adhesionAL amyloidosisAbnormality of the gastrointestinal tractneoplasmhepatocellular carcinoma
✦AI Summary

SAA1 (serum amyloid A1) is a major acute-phase protein synthesized predominantly by hepatocytes that functions as a key mediator of innate immunity and inflammation 1. As a lipophilic protein, SAA1 contributes to HDL and cholesterol transport while interacting with specific receptors including TLR4 to modulate immune responses 1. Mechanistically, SAA1 promotes pathogenic Th17 cell differentiation through direct T cell signaling in collaboration with STAT3-activating cytokines, and activates NF-κB signaling via TLR4/MD2 binding, triggering a feedforward inflammatory circuit 23. SAA1+ fibroblasts regulate macrophage infiltration and M1 polarization through chemokine secretion, supporting periodontal inflammation progression 4. Clinically, SAA1 elevation is associated with multiple inflammatory diseases: it exacerbates nonalcoholic fatty liver disease (NAFLD) through hepatic inflammation 3, contributes to colitis-related Th17 responses 5, and appears upregulated in psoriasis and atopic dermatitis sebaceous glands 6. Pathologically, SAA1 fragments can form insoluble amyloid fibrils causing secondary amyloidosis with renal manifestations in chr11 inflammatory disorders 7. These findings position SAA1 as a therapeutic target for inflammatory and metabolic diseases, with potential benefits from anti-SAA1 interventions in NAFLD, colitis, and periodontitis.

Sources cited
1
SAA1 is a major acute-phase protein synthesized by hepatocytes, functions in host defense, and contributes to HDL and cholesterol transport
PMID: 32189310
2
SAA1 promotes pathogenic Th17 cell differentiation acting directly on T cells with STAT3-activating cytokines
PMID: 31866067
3
SAA1 exacerbates NAFLD via TLR4/MD2-mediated NF-κB signaling activation, forming a feedforward regulatory circuit
PMID: 35247611
4
SAA1+ fibroblasts regulate macrophage infiltration and M1 polarization through chemokine secretion in periodontitis
PMID: 40775345
5
SAA1 and SAA2 are produced by gut epithelial cells in C/EBPA-dependent manner and promote Th17 cell differentiation in colitis
PMID: 37983567
6
SAA1 is a spatially variable inflammation-related gene expressed in sebaceous glands in psoriasis and atopic dermatitis
PMID: 38433843
7
SAA1 fragments form amyloid fibrils causing secondary amyloidosis with kidney involvement in chronic inflammatory disorders
PMID: 30274625
Disease Associationsⓘ20
AL amyloidosisOpen Targets
0.46Moderate
Abnormality of the gastrointestinal tractOpen Targets
0.22Weak
neoplasmOpen Targets
0.12Weak
hepatocellular carcinomaOpen Targets
0.12Weak
Parkinson diseaseOpen Targets
0.11Weak
SepsisOpen Targets
0.11Weak
COVID-19Open Targets
0.11Weak
Alzheimer diseaseOpen Targets
0.11Weak
glioblastoma multiformeOpen Targets
0.10Weak
lung cancerOpen Targets
0.10Weak
sarcoidosisOpen Targets
0.10Weak
type 2 diabetes mellitusOpen Targets
0.10Weak
colorectal carcinomaOpen Targets
0.10Weak
rheumatoid arthritisOpen Targets
0.10Suggestive
acute myeloid leukemiaOpen Targets
0.10Suggestive
gliomaOpen Targets
0.10Suggestive
triple-negative breast cancerOpen Targets
0.10Suggestive
achalasia-alacrima syndromeOpen Targets
0.10Suggestive
multiple system atrophyOpen Targets
0.10Suggestive
nonpapillary renal cell carcinomaOpen Targets
0.10Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LCATProtein interaction99%TLR4Protein interaction98%APOEProtein interaction97%HMGB1Protein interaction97%SAA2-SAA4Protein interaction91%APCSProtein interaction90%
Tissue Expression6 tissues
Liver
100%
Lung
0%
Ovary
0%
Brain
0%
Bone Marrow
0%
Heart
0%
Gene Interaction Network
Click a node to explore
SAA1LCATTLR4APOEHMGB1SAA2-SAA4APCS
PROTEIN STRUCTURE
Preparing viewer…
PDB4IP8 · 2.19 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.29LoF Tolerant
pLIⓘ
0.03Tolerant
Observed/Expected LoF0.66 [0.36–1.29]
RankingsWhere SAA1 stands among ~20K protein-coding genes
  • #1,141of 20,598
    Most Researched304 · top 10%
  • #13,611of 17,882
    Most Constrained (LOEUF)1.29
Genes detectedSAA1
Sources retrieved25 papers
Response time—
📄 Sources
25▼
1
Serum Amyloid A (SAA) Proteins.
PMID: 32189310
Subcell Biochem · 2020
1.00
2
Single-cell transcriptomic analysis highlights origin and pathological process of human endometrioid endometrial carcinoma.
PMID: 36273006
Nat Commun · 2022
0.90
3
Serum Amyloid A Proteins Induce Pathogenic Th17 Cells and Promote Inflammatory Disease.
PMID: 31866067
Cell · 2020
0.80
4
Serum amyloid A1 exacerbates hepatic steatosis via TLR4-mediated NF-κB signaling pathway.
PMID: 35247611
Mol Metab · 2022
0.70
5
Expression of SAA1, SAA2 and SAA4 genes in human primary monocytes and monocyte-derived macrophages.
PMID: 31100086
PLoS One · 2019
0.68