1. Gene Aliases

Serpin Family A Member 3, ACT, Alpha-1-Antichymotrypsin, AACT, Serpin Peptidase Inhibitor Clade A (Alpha-1 Antiproteinase; Antitrypsin) Member 3, Cell Growth-Inhibiting Gene 24/25 Protein, Serpin A3, Serine (Or Cysteine) Proteinase Inhibitor Clade A (Alpha-1 Antiproteinase; Antitrypsin) Member 3, Serine (Or Cysteine) Proteinase Inhibitor Clade A Member 3, Growth-Inhibiting Protein 24, Growth-Inhibiting Protein 25, Alpha-1 Antichymotrypsin, GIG24, GIG25

[https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERPINA3&keywords=Serpina3n#aliases_descriptions]

2. Association with Toxicity and/or Disease at a Transcriptional Level

3. Summary of Protein Family and Structure

4. Proteins Known to Interact with Gene Product

Interactions with experimental support

Interactions with text mining support

5. Links to Gene Databases

6. GO Terms, MSigDB Signatures, Pathways Containing Gene with Descriptions of Gene Sets

Pathways:

GO terms:

cellular response to cAMP [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cAMP (cyclic AMP, adenosine 3',5'-cyclophosphate) stimulus. GO:0071320]

cellular response to glucocorticoid stimulus [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a glucocorticoid stimulus. Glucocorticoids are hormonal C21 corticosteroids synthesized from cholesterol with the ability to bind with the cortisol receptor and trigger similar effects. Glucocorticoids act primarily on carbohydrate and protein metabolism, and have anti-inflammatory effects. GO:0071385]

cellular response to interleukin-1 [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-1 stimulus. GO:0071347]

cellular response to interleukin-6 [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interleukin-6 stimulus. GO:0071354]

cellular response to type II interferon [Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an interferon-gamma stimulus. Interferon gamma is the only member of the type II interferon found so far. GO:0071346]

response to bacterium [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a bacterium. GO:0009617]

response to cytokine [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cytokine stimulus. GO:0034097]

response to lipopolysaccharide [Any process that results in a change in state or activity of an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. GO:0032496]

response to peptide hormone [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a peptide hormone stimulus. A peptide hormone is any of a class of peptides that are secreted into the blood stream and have endocrine functions in living animals. GO:0043434]

response to vitamin B6 [Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin B6 stimulus. Vitamin B6 encompasses pyridoxal, pyridoxamine and pyridoxine and the active form, pyridoxal phosphate. GO:0034516]

MSigDB Signatures:

BLALOCK_ALZHEIMERS_DISEASE_UP: Genes up-regulated in brain from patients with Alzheimer's disease. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/BLALOCK_ALZHEIMERS_DISEASE_UP.html]

HSIAO_HOUSEKEEPING_GENES: Housekeeping genes identified as expressed across 19 normal tissues. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HSIAO_HOUSEKEEPING_GENES.html]

REACTOME_INNATE_IMMUNE_SYSTEM: Innate Immune System [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_INNATE_IMMUNE_SYSTEM.html]

COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP: Genes up-regulated in pilocytic astrocytoma compared to glioblastoma samples. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/COLIN_PILOCYTIC_ASTROCYTOMA_VS_GLIOBLASTOMA_UP.html]

HSIAO_LIVER_SPECIFIC_GENES: Liver selective genes [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/HSIAO_LIVER_SPECIFIC_GENES.html]

REACTOME_NEUTROPHIL_DEGRANULATION: Neutrophil degranulation [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_NEUTROPHIL_DEGRANULATION.html]

WP_VITAMIN_B12_METABOLISM: Vitamin B12 metabolism [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_VITAMIN_B12_METABOLISM.html]

REACTOME_HEMOSTASIS: Hemostasis [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/REACTOME_HEMOSTASIS.html]

WP_SELENIUM_MICRONUTRIENT_NETWORK: Selenium micronutrient network [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/WP_SELENIUM_MICRONUTRIENT_NETWORK.html]

PECE_MAMMARY_STEM_CELL_UP: The '3/3 signature': genes consistently up-regulated in all three pools of normal mammary stem cells (defined by their ability to retain the dye PKH26). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PECE_MAMMARY_STEM_CELL_UP.html]

MA_RAT_AGING_UP: Genes up-regulated across multiple cell types from nine tissues during rat aging. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MA_RAT_AGING_UP.html]

PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_6: Genes regulated in MCF7 cells (breast cancer) by expression of the full-length form of ERBB2 [GeneID=2064] at 60 h time point. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/PEDERSEN_METASTASIS_BY_ERBB2_ISOFORM_6.html]

SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_DN: Genes down-regulated in nasopharyngeal carcinoma (NPC) positive for LMP1 [GeneID=9260], a latent gene of Epstein-Barr virus (EBV). [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SENGUPTA_NASOPHARYNGEAL_CARCINOMA_WITH_LMP1_DN.html]

NABA_MATRISOME_HGSOC_OMENTAL_METASTASIS: Matrisome proteins detected in significantly different abundance in omentum metastases from high grade serous ovarian cancer (HGSOC) compared to normal omentum. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME_HGSOC_OMENTAL_METASTASIS.html]

KAAB_FAILED_HEART_VENTRICLE_DN: Genes down-regulated in the ventricles of failing hearts (DCM and ICM) compared to the healthy controls. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/KAAB_FAILED_HEART_VENTRICLE_DN.html]

MCCABE_BOUND_BY_HOXC6: Genes whose promoters where bound by HOXC6 [GeneID=3223] in LNCaP cells (prostate cancer), according to a ChIP-chip analysis. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MCCABE_BOUND_BY_HOXC6.html]

NABA_MATRISOME: Ensemble of genes encoding extracellular matrix and extracellular matrix-associated proteins [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/NABA_MATRISOME.html]

SCHOEN_NFKB_SIGNALING: Genes down-regulated in A375 cells (melanoma) treated with KINK-1, a small molecule inhibitor of NFKB. [https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/SCHOEN_NFKB_SIGNALING.html]

7. Gene Descriptions

NCBI Gene Summary: The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]

GeneCards Summary: SERPINA3 (Serpin Family A Member 3) is a Protein Coding gene. Diseases associated with SERPINA3 include Malignant Fibrous Histiocytoma and Alpha-1-Antitrypsin Deficiency. Among its related pathways are Response to elevated platelet cytosolic Ca2+ and Innate Immune System. Gene Ontology (GO) annotations related to this gene include serine-type endopeptidase inhibitor activity. An important paralog of this gene is SERPINA9.

UniProtKB/Swiss-Prot Summary: Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2.

8. Cellular Location of Gene Product

Positivity in extracellular deposits and cytoplasmic expression in a few cell types. Predicted location: Secreted, Intracellular (different isoforms) [https://www.proteinatlas.org/ENSG00000196136/subcellular]

9. Mechanistic Information

Summary

Serpina3n encodes a serpin family protein that inhibits serine proteases involved in inflammation and neuronal damage, such as cathepsin G, chymase, granzyme B, and neutrophil elastase [CS: 8]. Its protein product assists in maintaining vascular integrity by inactivating proteases that disrupt the blood-brain barrier (BBB) and reducing immune cell infiltration, thereby protecting neuronal tissue from inflammatory damage [CS: 8].

In response to brain injury or disease, the expression of Serpina3n is upregulated as part of the neuroinflammatory response mediated by cytokines like IL-6 [CS: 8]. This upregulation serves to curtail the harmful effects of enzymes released by activated immune cells, such as granzyme B and neutrophil elastase, which if uncontrolled could exacerbate BBB disruption and neuronal death [CS: 7]. In glioblastoma and neurodegenerative diseases like Alzheimer's, the increased presence of Serpina3n reflects an attempt to counteract the aggressive degradation of the extracellular matrix and protect neurons from excessive inflammation-induced apoptosis [CS: 6]. During incidents of brain trauma or ischemia, higher levels of Serpina3n help moderate the neuroinflammatory response by inhibiting deleterious proteolytic activity, ultimately aiming to preserve brain function and limit secondary injury [CS: 7].

10. Upstream Regulators

11. Tissues/Cell Type Where Genes are Overexpressed

Tissue type enchanced: liver, pancreas (group enriched) [https://www.proteinatlas.org/ENSG00000196136/tissue]

Cell type enchanced: ductal cells, exocrine glandular cells, fibroblasts, hepatocytes, mucus glandular cells, serous glandular cells (cell type enhanced) [https://www.proteinatlas.org/ENSG00000196136/single+cell+type]

12. Role of Gene in Other Tissues

13. Chemicals Known to Elicit Transcriptional Response of Biomarker in Tissue of Interest

Compounds that increase expression of the gene:

Compounds that decrease expression of the gene:

14. DisGeNet Biomarker Associations to Disease in Organ of Interest

Most relevant biomarkers with lower score or lower probability of association with disease or organ of interest: