CTSK Gene

HGNC Family	Cathepsins (CTS)
Name	cathepsin K
Description	The protein encoded by this gene is a lysosomal cysteine proteinase involved in bone remodeling and resorption. This protein, which is a member of the peptidase C1 protein family, is predominantly expressed in osteoclasts. However, the encoded protein is also expressed in a significant fraction of human breast cancers, where it could contribute to tumor invasiveness. Mutations in this gene are the cause of pycnodysostosis, an autosomal recessive disease characterized by osteosclerosis and short stature. [provided by RefSeq, Apr 2013]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cathepsin K (CTSK) is a potent lysosomal cysteine protease that is predominantly expressed and secreted by osteoclasts, where it plays a critical role in bone resorption by degrading type I collagen and other extracellular matrix proteins. This highly effective collagenolytic activity is, in part, enabled by its ability to form active complexes with glycosaminoglycans—an interaction that is unique among papain‐like cysteine proteases—thereby making CTSK the most powerful mammalian collagenase."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In animal models, deletion or selective inhibition of CTSK in osteoclasts markedly decreases bone resorption while simultaneously enhancing bone formation through osteoclast‐derived signals such as sphingosine‐1‐phosphate, indicating that CTSK is a key regulator in the coupling between bone degradation and formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Additionally, beyond its classical role in skeletal remodeling, CTSK has been implicated in modulating immune responses; its inhibition not only suppresses osteoclastic bone resorption but also dampens autoimmune inflammation by altering Toll‐like receptor signaling in dendritic cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Furthermore, in the context of joint disease such as rheumatoid arthritis, both osteoclasts and synovial fibroblasts express CTSK at sites of cartilage and bone degradation, where its activity facilitates the generation of aggrecan cleavage products that further potentiate matrix breakdown"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted role of CTSK in controlling bone and cartilage matrix turnover and illustrate its potential as a therapeutic target in disorders characterized by excessive bone resorption and joint destruction.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhenqiang Li, Yoshiyuki Yasuda, Weijie Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of collagenase activities of human cathepsins by glycosaminoglycans."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M310349200"}], "href": "https://doi.org/10.1074/jbc.M310349200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14645229"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14645229"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sutada Lotinun, Riku Kiviranta, Takuma Matsubara, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Osteoclast-specific cathepsin K deletion stimulates S1P-dependent bone formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI64840"}], "href": "https://doi.org/10.1172/JCI64840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23321671"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23321671"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Masataka Asagiri, Toshitake Hirai, Toshihiro Kunigami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin K-dependent toll-like receptor 9 signaling revealed in experimental arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1150110"}], "href": "https://doi.org/10.1126/science.1150110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18239127"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18239127"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Susan R Wilson, Christoph Peters, Paul Saftig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin K activity-dependent regulation of osteoclast actin ring formation and bone resorption."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M805280200"}], "href": "https://doi.org/10.1074/jbc.M805280200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19028686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19028686"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "W S Hou, Z Li, R E Gordon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cathepsin k is a critical protease in synovial fibroblast-mediated collagen degradation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/S0002-9440(10)63068-4"}], "href": "https://doi.org/10.1016/S0002-9440(10"}, {"type": "t", "text": "63068-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11733367"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11733367"}]}]}]}
Synonyms	PKND, PYCD, CTS02, CTSO, CTSO2
Proteins	CATK_HUMAN
NCBI Gene ID	1513
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CTSK has 10,381 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 119 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CTSK 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 CTSK gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CTSK protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CTSK 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 CTSK gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CTSK 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 CTSK gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with CTSK gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with CTSK gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CTSK gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CTSK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CTSK protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with CTSK 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 CTSK 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 CTSK gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CTSK gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CTSK gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CTSK gene/protein from the curated CTD Gene-Disease Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CTSK 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 CTSK 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 CTSK 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 CTSK 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 CTSK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CTSK gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for CTSK protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at CTSK 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 CTSK gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CTSK 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 CTSK from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with CTSK gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.