Details for: SAA2

Gene ID: 6289

Gene Type:  Protein-coding  - A gene that serves as a template for producing a messenger RNA (mRNA) molecule, which is then translated into a functional protein.

Symbol: SAA2

Ensembl ID: ENSG00000134339

Description: serum amyloid A2

Selected Context(s):  Lung + Healthy

Cell Significance Landscape

Contexts:

Associated with

Significant Cells

Cell Significance Index (CSI) scores for the chosen context(s)

  • club cell CL0000158
    CSI 102.87
    rCSI 84.87%
    PRS 97.37

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.
Network Configuration

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  • Node Color (Target Cell CSI, relative to current network):
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  • Node Size: Proportional to Target Cell CSI magnitude
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Other Information

This section provides additional information about the gene, including a description generated by an AI language model and details about associated proteins.

## Summary Analyzed for its specificity (CSI Z-Score), Serum Amyloid A2 ([SAA2](/details-gene/6289)) is an acute-phase reactant protein whose expression appears highly restricted to [club cell](/details-cell/CL0000158)s within the **Lung + Healthy** tissue context. While its expression pattern is exclusive to this cell type, suggesting a role as a potential specificity marker, the low statistical confidence in the current dataset indicates that this finding warrants further investigation. Its established role in the inflammatory response suggests its function in club cells may be tied to local immune surveillance in the airways. ## Cellular Roles and Expression Landscape The primary role of [SAA2](/details-gene/6289) as a cell type-specific marker is evaluated through its expression profile in the **Lung + Healthy** context. The analysis reveals a remarkable degree of specificity for [club cell](/details-cell/CL0000158)s. This is underscored by a perfect Effect Size (deltaVal: 1.00), which indicates that, within the limits of detection in this dataset, [SAA2](/details-gene/6289) transcripts are exclusively found in this cell type and are absent from all others. This high degree of specificity is further supported by a high Percentile Rank Score (PRS: 97.37%), placing it among the top 3% of genes for this specificity metric. However, this conclusion is tempered by other statistical measures. The CSI (Z-SCORE) of 0.00 is neutral, and the associated p-value of 0.660 is not statistically significant. This combination of perfect specificity but weak statistical support suggests that [SAA2](/details-gene/6289) expression in healthy club cells may be either at a very low level, highly variable between individuals, or restricted to a very small and rare subpopulation of these cells, making the signal difficult to distinguish from noise. Therefore, while the data strongly point towards [SAA2](/details-gene/6289) as a highly specific marker for [club cell](/details-cell/CL0000158)s, its utility as a robust marker in a healthy state requires more sensitive validation. ## Pathways and Molecular Function The known functions of [SAA2](/details-gene/6289) provide a framework for interpreting its specific expression in [club cell](/details-cell/CL0000158)s. [SAA2](/details-gene/6289) is a well-documented member of the SAA family of apolipoproteins, which are strongly induced during the systemic [acute-phase response](/details-go/GO:0006953) to inflammation, as established by multiple studies ([PubMed: 3183061](https://pubmed.ncbi.nlm.nih.gov/3183061/), [PubMed: 1656519](https://pubmed.ncbi.nlm.nih.gov/1656519/)). It is primarily known to be secreted by the liver into the bloodstream, where it associates with [high-density lipoprotein particle](/details-go/GO:0034364)s. Its specific expression in pulmonary [club cell](/details-cell/CL0000158)s in a non-inflamed, healthy state suggests a potential role in local, tissue-level processes distinct from the systemic response. Club cells are secretory cells critical for bronchiolar defense and regeneration. The presence of [SAA2](/details-gene/6289) in this cell type may indicate its involvement in local immune surveillance, antimicrobial defense, or lipid-mediated signaling within the airway microenvironment. Its secretion as part of the [extracellular exosome](/details-go/GO:0070062) component could facilitate communication with nearby immune or epithelial cells, priming the local environment for a rapid response to pathogens or irritants. ## Research Directions The specific and potentially low-level expression of [SAA2](/details-gene/6289) in healthy lung club cells opens several avenues for future research, particularly concerning its dynamics during inflammation and its precise functional contribution to airway biology. ### Testable Hypotheses: 1. **Hypothesis:** Basal [SAA2](/details-gene/6289) expression in [club cell](/details-cell/CL0000158)s represents a state of readiness, and its transcription is rapidly and substantially upregulated upon local inflammatory stimuli, such as viral or bacterial infection. * **Experimental Approach:** Utilize single-cell RNA sequencing and in situ hybridization on lung tissue from mouse models challenged with influenza virus or lipopolysaccharide (LPS). This would quantify the change in `Saa2` transcript levels and the proportion of expressing club cells compared to saline-treated controls. 2. **Hypothesis:** The statistically weak signal for [SAA2](/details-gene/6289) in the healthy lung is because its expression marks a rare, specialized sub-population of [club cell](/details-cell/CL0000158)s dedicated to innate immune sensing. * **Experimental Approach:** Perform deep single-cell transcriptomic profiling on sorted lung epithelial cells (e.g., EpCAM+) from multiple healthy human donors. Computationally isolate the `SAA2`-positive club cell cluster and perform differential expression analysis to identify a unique co-expressed gene signature related to pattern recognition receptors or other immune-modulatory factors. 3. **Hypothesis:** Secreted [SAA2](/details-gene/6289) from [club cell](/details-cell/CL0000158)s functions locally within the airways to modulate surfactant properties or exert direct antimicrobial activity. * **Experimental Approach:** Generate a conditional knockout mouse model with `Saa2` deleted specifically in club cells (e.g., using a `Scgb1a1-Cre` driver). Analyze the protein and lipid composition of bronchoalveolar lavage fluid (BALF) at baseline and after an infectious challenge. Assess the susceptibility of these mice to respiratory pathogens compared to wild-type littermates. ### Therapeutic Potential: Given its highly specific expression profile, [SAA2](/details-gene/6289) could serve as a sensitive biomarker. Measuring [SAA2](/details-gene/6289) protein levels in BALF or sputum may provide a specific readout of club cell stress or activation in diseases like COPD, asthma, or early-stage lung infections. Furthermore, if SAA2's function during chronic inflammation is found to be pathogenic, developing inhaled therapeutics that specifically block [SAA2](/details-gene/6289) activity or its downstream signaling in the airways could offer a targeted treatment strategy with minimal systemic side effects.

Genular Protein ID: 2739850487

Symbol: SAA2_HUMAN

Name: N/A

UniProtKB Accession Codes:

P0DJI9 G3XAK9 P02735 P02736 P02737 Q16730 Q16834 Q16835 Q16879 Q3KRB3 Q6FG67 Q96QN0 Q9UCK9 Q9UCL0

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 2 CTD 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 12 Ensembl 4 ExpressionAtlas 1 GO 3 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 GlyGen 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 1 KEGG 1 MANE-Select 1 MIM 1 MassIVE 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PIRSF 1 PRINTS 1 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 2 RNAct 1 RefSeq 2 SMART 1 SMR 1 STRING 1 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 3800865

Title: DNA sequence evidence for polymorphic forms of human serum amyloid A (SAA).

PubMed ID: 3800865

DOI: 10.1007/bf00554519

PubMed ID: 2890635

Title: Structure of a human serum amyloid A gene and modulation of its expression in transfected L cells.

PubMed ID: 2890635

DOI: 10.1016/s0021-9258(18)47798-8

PubMed ID: 3183061

Title: Human serum amyloid A. Three hepatic mRNAs and the corresponding proteins in one person.

PubMed ID: 3183061

DOI: 10.1172/jci113779

PubMed ID: 1971508

Title: Heterogeneity of human serum amyloid A protein. Five different variants from one individual demonstrated by cDNA sequence analysis.

PubMed ID: 1971508

DOI: 10.1042/bj2680187

PubMed ID: 14702039

Title: Complete sequencing and characterization of 21,243 full-length human cDNAs.

PubMed ID: 14702039

DOI: 10.1038/ng1285

PubMed ID: 16554811

Title: Human chromosome 11 DNA sequence and analysis including novel gene identification.

PubMed ID: 16554811

DOI: 10.1038/nature04632

PubMed ID: 15489334

Title: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).

PubMed ID: 15489334

DOI: 10.1101/gr.2596504

PubMed ID: 1463770

Title: Identification of two novel amyloid A protein subsets coexisting in an individual patient of AA-amyloidosis.

PubMed ID: 1463770

DOI: 10.1016/0925-4439(92)90068-x

PubMed ID: 1656519

Title: The human acute-phase serum amyloid A gene family: structure, evolution and expression in hepatoma cells.

PubMed ID: 1656519

DOI: 10.1111/j.1365-3083.1991.tb01570.x

PubMed ID: 10211414

Title: Revised nomenclature for serum amyloid A (SAA). Nomenclature Committee of the International Society of Amyloidosis. Part 2.

PubMed ID: 10211414

DOI: 10.3109/13506129908993291

Sequence Information:

  • Length: 122
  • Mass: 13527
  • Checksum: C4AAB684E0EDCBB8
  • Sequence:
    • MKLLTGLVFC SLVLSVSSRS FFSFLGEAFD GARDMWRAYS DMREANYIGS DKYFHARGNY 
DAAKRGPGGA WAAEVISNAR ENIQRLTGRG AEDSLADQAA NKWGRSGRDP NHFRPAGLPE 
KY