CTSS Gene

HGNC Family	Cathepsins (CTS)
Name	cathepsin S
Description	The preproprotein encoded by this gene, a member of the peptidase C1 family, is a lysosomal cysteine proteinase that participates in the degradation of antigenic proteins to peptides for presentation on MHC class II molecules. The mature protein cleaves the invariant chain of MHC class II molecules in endolysosomal compartments and enables the formation of antigen-MHC class II complexes and the proper display of extracellular antigenic peptides by MHC-II. The mature protein also functions as an elastase over a broad pH range. When secreted from cells, this protein can remodel components of the extracellular matrix such as elastin, collagen, and fibronectin. This gene is implicated in the pathology of many inflammatory and autoimmune diseases and, given its elastase activity, plays a significant role in some pulmonary diseases. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2020]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cathepsin S (CTSS) is a lysosomal cysteine protease with multifaceted roles in extracellular matrix remodeling, immune regulation, and metabolic homeostasis. Several studies have demonstrated that CTSS‐mediated proteolysis contributes to tumor progression by facilitating cellular invasion and metastasis. For example, CTSS cleaves junctional adhesion molecules to promote blood–brain barrier transmigration in breast‐to‐brain metastasis, and its secretion by tumor‐initiating cells regulates protease‐activated receptor 2 (PAR2) signaling, thereby modulating tumor initiation, self‐renewal, and metastatic spread ."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the immune system, CTSS is emerging as an important mediator of neuroimmune and autoimmune processes. Alterations in CTSS expression have been linked to changes in behavioral phenotypes such as alcohol consumption—in which deletion of Ctss reduces ethanol intake—and to disease activity in multiple sclerosis, where elevated CTSS levels in blood and altered CTSS gene polymorphisms correlate with treatment response (e.g., to interferon‐β or glatiramer acetate) ."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CTSS also plays a significant role in metabolic regulation. It promotes adipogenesis by degrading extracellular matrix proteins such as fibronectin, a step required for preadipocyte differentiation. Likewise, changes in CTSS expression within adipose tissue have been associated with obesity and its improvement following weight loss ."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Additionally, CTSS mRNA is subject to extensive post‐transcriptional editing in endothelial cells, suggesting a regulatory mechanism that may contribute to vascular pathology ."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " In other settings, aberrant expression of CTSS has been implicated in conditions such as EBV‐associated lymphomas and even in skin inflammation resembling chronic atopic dermatitis, highlighting the protease’s broad impact on diverse pathologic processes ."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the importance of CTSS as a multifunctional enzyme that modulates extracellular proteolysis, immune cell activation, and metabolic differentiation. Its diverse roles in cancer metastasis, neuroimmune signaling, autoimmune activity, and adipogenesis make CTSS a promising therapeutic target in oncology, inflammatory diseases, and metabolic disorders (1,3,4,6,7,8,10,11,12,13,14).\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lisa Sevenich, Robert L Bowman, Steven D Mason, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Analysis of tumour- and stroma-supplied proteolytic networks reveals a brain-metastasis-promoting role for cathepsin S."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Cell Biol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncb3011"}], "href": "https://doi.org/10.1038/ncb3011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25086747"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25086747"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Terence Kin-Wah Lee, Vincent Chi-Ho Cheung, Ping Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Blockade of CD47-mediated cathepsin S/protease-activated receptor 2 signaling provides a therapeutic target for hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.27070"}], "href": "https://doi.org/10.1002/hep.27070"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24523067"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24523067"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Min-Chieh Hsin, Yi-Hsien Hsieh, Po-Hui Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hispolon suppresses metastasis via autophagic degradation of cathepsin S in cervical cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2017.459"}], "href": "https://doi.org/10.1038/cddis.2017.459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28981104"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28981104"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yuri A Blednov, Igor Ponomarev, Chelsea Geil, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuroimmune regulation of alcohol consumption: behavioral validation of genes obtained from genomic studies."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Addict Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1369-1600.2010.00284.x"}], "href": "https://doi.org/10.1111/j.1369-1600.2010.00284.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21309947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21309947"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Dana Haves-Zburof, Tamar Paperna, Alumit Gour-Lavie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsins and their endogenous inhibitors cystatins: expression and modulation in multiple sclerosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Mol Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1582-4934.2010.01229.x"}], "href": "https://doi.org/10.1111/j.1582-4934.2010.01229.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21143385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21143385"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Stephen Cunningham, Colin Graham, Michael Hutchinson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenomics of responsiveness to interferon IFN-beta treatment in multiple sclerosis: a genetic screen of 100 type I interferon-inducible genes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Pharmacol Ther (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.clpt.2005.08.018"}], "href": "https://doi.org/10.1016/j.clpt.2005.08.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16338279"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16338279"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Iris Grossman, Nili Avidan, Clara Singer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Pharmacogenetics of glatiramer acetate therapy for multiple sclerosis reveals drug-response markers."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacogenet Genomics (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/FPC.0b013e3281299169"}], "href": "https://doi.org/10.1097/FPC.0b013e3281299169"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17622942"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17622942"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Soraya Taleb, Raffaella Cancello, Karine Clément, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin s promotes human preadipocyte differentiation: possible involvement of fibronectin degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2006-0386"}], "href": "https://doi.org/10.1210/en.2006-0386"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16825321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16825321"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Soraya Taleb, Raffaella Cancello, Christine Poitou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Weight loss reduces adipose tissue cathepsin S and its circulating levels in morbidly obese women."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Endocrinol Metab (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/jc.2005-1601"}], "href": "https://doi.org/10.1210/jc.2005-1601"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16394095"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16394095"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Konstantinos Stellos, Aikaterini Gatsiou, Kimon Stamatelopoulos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adenosine-to-inosine RNA editing controls cathepsin S expression in atherosclerosis by enabling HuR-mediated post-transcriptional regulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Med (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/nm.4172"}], "href": "https://doi.org/10.1038/nm.4172"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27595325"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27595325"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Sinéad Weldon, Paul McNally, Danny F McAuley, et al. "}, {"type": "b", "children": [{"type": "t", "text": "miR-31 dysregulation in cystic fibrosis airways contributes to increased pulmonary cathepsin S production."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.201311-1986OC"}], "href": "https://doi.org/10.1164/rccm.201311-1986OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24940638"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24940638"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Elie Dheilly, Elena Battistello, Natalya Katanayeva, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin S Regulates Antigen Processing and T Cell Activity in Non-Hodgkin Lymphoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Cell (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ccell.2020.03.016"}], "href": "https://doi.org/10.1016/j.ccell.2020.03.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32330455"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32330455"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Nari Kim, Ki Beom Bae, Myoung Ok Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of cathepsin S induces chronic atopic dermatitis in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2011.404"}], "href": "https://doi.org/10.1038/jid.2011.404"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22170489"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22170489"}]}]}]}
Proteins	CATS_HUMAN
NCBI Gene ID	1520
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CTSS has 12,051 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 127 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CTSS Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CTSS gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of CTSS gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 CTSS 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 CTSS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of CTSS gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of CTSS gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of CTSS 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 CTSS gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of CTSS gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of CTSS gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CTSS 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 CTSS gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with CTSS gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CTSS protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CTSS 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 CTSS gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CTSS 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 CTSS 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 CTSS gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CTSS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CTSS protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CTSS protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing CTSS protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CTSS 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 CTSS 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 CTSS gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CTSS gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CTSS gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CTSS gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CTSS gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with CTSS gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CTSS 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 CTSS 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 CTSS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CTSS gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CTSS protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CTSS 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 CTSS gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CTSS gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing CTSS from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.