CST2 Gene

Name cystatin SA
Description The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins and the kininogens. The type 2 cystatin proteins are a class of cysteine proteinase inhibitors found in a variety of human fluids and secretions, where they appear to provide protective functions. The cystatin locus on chromosome 20 contains the majority of the type 2 cystatin genes and pseudogenes. This gene is located in the cystatin locus and encodes a secreted thiol protease inhibitor found at high levels in saliva, tears and seminal plasma. [provided by RefSeq, Jul 2008]
Summary
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cystatin 2 (CST2), a member of the cystatin superfamily of cysteine protease inhibitors, has emerged as a significant biomarker with diverse functional implications in both cancer and chronic inflammatory airway diseases. In the oncologic arena, CST2 is aberrantly overexpressed in several malignancies. Elevated CST2 mRNA and protein levels in prostate, gastric, and colorectal cancers have been associated with advanced tumor stage, enhanced tumor cell proliferation, migration, invasion, and metastatic progression, ultimately correlating with poorer overall survival outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " For example, in gastric cancer, CST2 over‐expression was shown to modulate the epithelial–mesenchymal transition and TGF‐β1 signaling pathway, thereby promoting aggressive behavior, while its inclusion in a multi‐gene transcript signature improved the prognostic stratification of patients with prostate cancer. Similarly, in colorectal cancer, increased CST2 expression in tumor tissues, including adenoma and metastatic lesions, was significantly correlated with a shorter overall survival, underscoring its potential utility as a diagnostic and prognostic biomarker.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its role in cancer, CST2 has also been detected in nasal secretions, where its expression appears to reflect the severity of chronic inflammatory airway disorders. Measurements of CST2 in nasal mucus and exosome‐enriched fractions have revealed that higher levels are associated with chronic rhinosinusitis with nasal polyps (CRSwNP) and correlate with clinical parameters—for instance, segregating patients with more severe comorbid phenotypes such as asthma, tissue eosinophilia, and aspirin-exacerbated respiratory disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Although not all differences reach statistical significance, these findings support the notion that CST2 may serve as a noninvasive biomarker to differentiate disease phenotypes and monitor inflammatory severity in airway disorders.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies suggest that CST2 plays a multifaceted role—it not only contributes to tumor progression in various cancer types through potential modulation of protease activity and signaling pathways but also reflects inflammatory status in chronic airway disease. Further investigation into CST2’s molecular mechanisms may offer additional insights for targeted therapeutic interventions and improved patient stratification in both oncology and chronic inflammatory conditions.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anqi Cheng, Shanshan Zhao, Liesel M FitzGerald, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A four-gene transcript score to predict metastatic-lethal progression in men treated for localized prostate cancer: Development and validation studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostate (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/pros.23882"}], "href": "https://doi.org/10.1002/pros.23882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31376183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31376183"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "W P Zhang, Y Wang, D Tan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cystatin 2 leads to a worse prognosis in patients with gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Regul Homeost Agents (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.23812/20-293-A"}], "href": "https://doi.org/10.23812/20-293-A"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33302616"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33302616"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Patricia Dehon Mott, Christopher M Taylor, Rebecca A Lillis, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differences in the Genital Microbiota in Women Who Naturally Clear "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "Chlamydia trachomatis"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " Infection Compared to Women Who Do Not Clear; A Pilot Study."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Cell Infect Microbiol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fcimb.2021.615770"}], "href": "https://doi.org/10.3389/fcimb.2021.615770"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33912473"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33912473"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Sarina K Mueller, Olaf Wendler, Angela Nocera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Escalation in mucus cystatin 2, pappalysin-A, and periostin levels over time predict need for recurrent surgery in chronic rhinosinusitis with nasal polyps."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Forum Allergy Rhinol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/alr.22407"}], "href": "https://doi.org/10.1002/alr.22407"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31430426"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31430426"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Michelle M Miyake, Alan D Workman, Angela L Nocera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Discriminant analysis followed by unsupervised cluster analysis including exosomal cystatins predict presence of chronic rhinosinusitis, phenotype, and disease severity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int Forum Allergy Rhinol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/alr.22380"}], "href": "https://doi.org/10.1002/alr.22380"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31322841"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31322841"}]}]}]}
Proteins CYTT_HUMAN
NCBI Gene ID 1470
API
Download Associations
Predicted Functions View CST2's ARCHS4 Predicted Functions.
Co-expressed Genes View CST2's ARCHS4 Predicted Functions.
Expression in Tissues and Cell Lines View CST2's ARCHS4 Predicted Functions.

Functional Associations

CST2 has 2,130 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 90 datasets.

Click the + buttons to view associations for CST2 from the datasets below.

If available, associations are ranked by standardized value

Dataset Summary
Achilles Cell Line Gene Essentiality Profiles cell lines with fitness changed by CST2 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles tissues with high or low expression of CST2 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CST2 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray tissue samples with high or low expression of CST2 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
BioGPS Cell Line Gene Expression Profiles cell lines with high or low expression of CST2 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
BioGPS Human Cell Type and Tissue Gene Expression Profiles cell types and tissues with high or low expression of CST2 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
Carcinogenome Chemical Perturbation Carcinogenicity Signatures small molecule perturbations changing expression of CST2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
CCLE Cell Line Gene CNV Profiles cell lines with high or low copy number of CST2 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
CCLE Cell Line Gene Expression Profiles cell lines with high or low expression of CST2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
CellMarker Gene-Cell Type Associations cell types associated with CST2 gene from the CellMarker Gene-Cell Type Associations dataset.
ChEA Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CST2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
ChEA Transcription Factor Targets transcription factors binding the promoter of CST2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
ChEA Transcription Factor Targets 2022 transcription factors binding the promoter of CST2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CST2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores cellular components containing CST2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
COMPARTMENTS Curated Protein Localization Evidence Scores 2025 cellular components containing CST2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores cellular components co-occuring with CST2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 cellular components co-occuring with CST2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
COSMIC Cell Line Gene CNV Profiles cell lines with high or low copy number of CST2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
COSMIC Cell Line Gene Mutation Profiles cell lines with CST2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
DepMap CRISPR Gene Dependency cell lines with fitness changed by CST2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
DISEASES Experimental Gene-Disease Association Evidence Scores diseases associated with CST2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores diseases co-occuring with CST2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 diseases co-occuring with CST2 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
DisGeNET Gene-Disease Associations diseases associated with CST2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
DisGeNET Gene-Phenotype Associations phenotypes associated with CST2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
ENCODE Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CST2 gene from the ENCODE Histone Modification Site Profiles dataset.
ENCODE Transcription Factor Binding Site Profiles transcription factor binding site profiles with transcription factor binding evidence at the promoter of CST2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
ENCODE Transcription Factor Targets transcription factors binding the promoter of CST2 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
GAD Gene-Disease Associations diseases associated with CST2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
GAD High Level Gene-Disease Associations diseases associated with CST2 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
GDSC Cell Line Gene Expression Profiles cell lines with high or low expression of CST2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
GeneRIF Biological Term Annotations biological terms co-occuring with CST2 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
GeneSigDB Published Gene Signatures PubMedIDs of publications reporting gene signatures containing CST2 from the GeneSigDB Published Gene Signatures dataset.
GEO Signatures of Differentially Expressed Genes for Diseases disease perturbations changing expression of CST2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
GEO Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CST2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Kinase Perturbations kinase perturbations changing expression of CST2 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CST2 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset.
GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations transcription factor perturbations changing expression of CST2 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset.
GEO Signatures of Differentially Expressed Genes for Viral Infections virus perturbations changing expression of CST2 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset.
GO Biological Process Annotations 2015 biological processes involving CST2 gene from the curated GO Biological Process Annotations 2015 dataset.
GO Biological Process Annotations 2023 biological processes involving CST2 gene from the curated GO Biological Process Annotations 2023 dataset.
GO Biological Process Annotations 2025 biological processes involving CST2 gene from the curated GO Biological Process Annotations2025 dataset.
GO Cellular Component Annotations 2015 cellular components containing CST2 protein from the curated GO Cellular Component Annotations 2015 dataset.
GO Cellular Component Annotations 2023 cellular components containing CST2 protein from the curated GO Cellular Component Annotations 2023 dataset.
GO Cellular Component Annotations 2025 cellular components containing CST2 protein from the curated GO Cellular Component Annotations 2025 dataset.
GO Molecular Function Annotations 2015 molecular functions performed by CST2 gene from the curated GO Molecular Function Annotations 2015 dataset.
GO Molecular Function Annotations 2023 molecular functions performed by CST2 gene from the curated GO Molecular Function Annotations 2023 dataset.
GO Molecular Function Annotations 2025 molecular functions performed by CST2 gene from the curated GO Molecular Function Annotations 2025 dataset.
GTEx eQTL 2025 SNPs regulating expression of CST2 gene from the GTEx eQTL 2025 dataset.
GTEx Tissue Gene Expression Profiles tissues with high or low expression of CST2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset.
GTEx Tissue Gene Expression Profiles 2023 tissues with high or low expression of CST2 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset.
GWAS Catalog SNP-Phenotype Associations 2025 phenotypes associated with CST2 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset.
GWASdb SNP-Disease Associations diseases associated with CST2 gene in GWAS and other genetic association datasets from the GWASdb SNP-Disease Associations dataset.
GWASdb SNP-Phenotype Associations phenotypes associated with CST2 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset.
Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles cell lines with high or low expression of CST2 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset.
HPA Tissue Gene Expression Profiles tissues with high or low expression of CST2 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset.
HPA Tissue Protein Expression Profiles tissues with high or low expression of CST2 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset.
HPA Tissue Sample Gene Expression Profiles tissue samples with high or low expression of CST2 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset.
HuGE Navigator Gene-Phenotype Associations phenotypes associated with CST2 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset.
InterPro Predicted Protein Domain Annotations protein domains predicted for CST2 protein from the InterPro Predicted Protein Domain Annotations dataset.
JASPAR Predicted Human Transcription Factor Targets 2025 transcription factors regulating expression of CST2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset.
JASPAR Predicted Transcription Factor Targets transcription factors regulating expression of CST2 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset.
KEGG Pathways 2026 pathways involving CST2 protein from the KEGG Pathways 2026 dataset.
Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles cell lines with high or low copy number of CST2 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset.
KnockTF Gene Expression Profiles with Transcription Factor Perturbations transcription factor perturbations changing expression of CST2 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset.
LINCS L1000 CMAP Chemical Perturbation Consensus Signatures small molecule perturbations changing expression of CST2 gene from the LINCS L1000 CMAP Chemical Perturbations Consensus Signatures dataset.
LINCS L1000 CMAP CRISPR Knockout Consensus Signatures gene perturbations changing expression of CST2 gene from the LINCS L1000 CMAP CRISPR Knockout Consensus Signatures dataset.
LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules small molecule perturbations changing expression of CST2 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
LOCATE Predicted Protein Localization Annotations cellular components predicted to contain CST2 protein from the LOCATE Predicted Protein Localization Annotations dataset.
MiRTarBase microRNA Targets microRNAs targeting CST2 gene in low- or high-throughput microRNA targeting studies from the MiRTarBase microRNA Targets dataset.
MotifMap Predicted Transcription Factor Targets transcription factors regulating expression of CST2 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset.
MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations gene perturbations changing expression of CST2 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset.
NIBR DRUG-seq U2OS MoA Box Gene Expression Profiles drug perturbations changing expression of CST2 gene from the NIBR DRUG-seq U2OS MoA Box dataset.
Pathway Commons Protein-Protein Interactions interacting proteins for CST2 from the Pathway Commons Protein-Protein Interactions dataset.
PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations gene perturbations changing expression of CST2 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset.
PFOCR Pathway Figure Associations 2023 pathways involving CST2 protein from the PFOCR Pathway Figure Associations 2023 dataset.
PFOCR Pathway Figure Associations 2024 pathways involving CST2 protein from the Wikipathways PFOCR 2024 dataset.
Roadmap Epigenomics Histone Modification Site Profiles histone modification site profiles with high histone modification abundance at CST2 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset.
RummaGEO Drug Perturbation Signatures drug perturbations changing expression of CST2 gene from the RummaGEO Drug Perturbation Signatures dataset.
RummaGEO Gene Perturbation Signatures gene perturbations changing expression of CST2 gene from the RummaGEO Gene Perturbation Signatures dataset.
Sci-Plex Drug Perturbation Signatures drug perturbations changing expression of CST2 gene from the Sci-Plex Drug Perturbation Signatures dataset.
TargetScan Predicted Nonconserved microRNA Targets microRNAs regulating expression of CST2 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset.
TCGA Signatures of Differentially Expressed Genes for Tumors tissue samples with high or low expression of CST2 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores tissues with high expression of CST2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset.
TISSUES Curated Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CST2 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores tissues with high expression of CST2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset.
TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 tissues with high expression of CST2 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores tissues co-occuring with CST2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset.
TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 tissues co-occuring with CST2 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset.