CSTB Gene

Name	cystatin B (stefin B)
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 kininogens. This gene encodes a stefin that functions as an intracellular thiol protease inhibitor. The protein is able to form a dimer stabilized by noncovalent forces, inhibiting papain and cathepsins l, h and b. The protein is thought to play a role in protecting against the proteases leaking from lysosomes. Evidence indicates that mutations in this gene are responsible for the primary defects in patients with progressive myoclonic epilepsy (EPM1). One type of mutation responsible for EPM1 is the expansion in the promoter region of this gene of a CCCCGCCCCGCG repeat from 2-3 copies to 30-78 copies. [provided by RefSeq, Jul 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Cystatin B (CSTB), also known as stefin B, is a key endogenous inhibitor of cysteine proteases, most notably the lysosomal cathepsins B, L, and S."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " CSTB helps maintain cellular homeostasis by modulating proteolytic activity; for example, its interaction with nucleosomes and histones in the nucleus leads to inhibition of cathepsin L activity and a consequent delay in cell cycle progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Loss‐of‐function mutations or markedly reduced expression of CSTB underlie progressive myoclonus epilepsy of Unverricht–Lundborg type (EPM1), a neurodegenerative disorder characterized by increased cathepsin activity, oxidative stress, neuroinflammation, and premature neuronal apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "6"}]}, {"type": "t", "text": " In addition, CSTB displays a propensity to form amyloid fibrils under specific conditions, suggesting that its misfolded aggregates may contribute to neurodegenerative cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Beyond its roles in the central nervous system, altered CSTB expression is observed in tumorigenesis; for instance, CSTB is overexpressed in hepatocellular carcinoma tissues and found elevated in patient sera, and its levels correlate with those of tau protein in neuroblastoma models, indicating potential diagnostic and prognostic utility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "10"}]}, {"type": "t", "text": " Collectively, these findings underscore the multifaceted roles of CSTB in regulating lysosomal proteolysis, protecting neuronal integrity, and modulating cell cycle dynamics—with its dysregulation contributing to both neurodegenerative disease and tumor progression"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "–."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Maria K Lehtinen, Saara Tegelberg, Hyman Schipper, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cystatin B deficiency sensitizes neurons to oxidative stress in progressive myoclonus epilepsy, EPM1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.0682-09.2009"}], "href": "https://doi.org/10.1523/JNEUROSCI.0682-09.2009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19420257"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19420257"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Slavko Čeru, Špela Konjar, Katarina Maher, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Stefin B interacts with histones and cathepsin L in the nucleus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.034793"}], "href": "https://doi.org/10.1074/jbc.M109.034793"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20075068"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20075068"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Riitta Rinne, Pekka Saukko, Mikko Järvinen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduced cystatin B activity correlates with enhanced cathepsin activity in progressive myoclonus epilepsy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Med (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/078538902320772124"}], "href": "https://doi.org/10.1080/078538902320772124"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12452481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12452481"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Patrick Shannon, Len A Pennacchio, Megan K Houseweart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Neuropathological changes in a mouse model of progressive myoclonus epilepsy: cystatin B deficiency and Unverricht-Lundborg disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neuropathol Exp Neurol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jnen/61.12.1085"}], "href": "https://doi.org/10.1093/jnen/61.12.1085"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12484571"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12484571"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Tarja Joensuu, Mervi Kuronen, Kirsi Alakurtti, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cystatin B: mutation detection, alternative splicing and expression in progressive myclonus epilepsy of Unverricht-Lundborg type (EPM1) patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.ejhg.5201723"}], "href": "https://doi.org/10.1038/sj.ejhg.5201723"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17003839"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17003839"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Olesya Okuneva, Inken Körber, Zhilin Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Abnormal microglial activation in the Cstb(-/-) mouse, a model for progressive myoclonus epilepsy, EPM1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.22760"}], "href": "https://doi.org/10.1002/glia.22760"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25327891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25327891"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Gregor Anderluh, Ion Gutierrez-Aguirre, Sabina Rabzelj, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of human stefin B in the prefibrillar oligomeric form with membranes. Correlation with cellular toxicity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1742-4658.2005.04717.x"}], "href": "https://doi.org/10.1111/j.1742-4658.2005.04717.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15955063"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15955063"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Urška Verbovšek, Helena Motaln, Ana Rotter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression analysis of all protease genes reveals cathepsin K to be overexpressed in glioblastoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0111819"}], "href": "https://doi.org/10.1371/journal.pone.0111819"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25356585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25356585"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mi-Jin Lee, Gyung-Ran Yu, Seon-Hwa Park, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of cystatin B as a potential serum marker in hepatocellular carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-07-1615"}], "href": "https://doi.org/10.1158/1078-0432.CCR-07-1615"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18281540"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18281540"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "C Geeth Gunawardana, Mohadeseh Mehrabian, Xinzhu Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M115.050724"}], "href": "https://doi.org/10.1074/mcp.M115.050724"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26269332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26269332"}]}]}]}
Synonyms	EPM1A, PME, CST6, ULD, STFB, EPM1, CPI-B
Proteins	CYTB_HUMAN
NCBI Gene ID	1476
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

CSTB has 9,389 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 120 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

CSTB Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by CSTB 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 CSTB 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 CSTB gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of CSTB 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 CSTB 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 CSTB 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 CSTB 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 CSTB 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 CSTB gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of CSTB 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 CSTB gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with CSTB protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with CSTB 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 CSTB gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of CSTB 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 CSTB 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 CSTB gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of CSTB gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing CSTB protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing CSTB protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing CSTB 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 CSTB 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 CSTB 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 CSTB 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 CSTB gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with CSTB gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with CSTB gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with CSTB gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of CSTB protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by CSTB gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving CSTB gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving CSTB gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with CSTB 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 CSTB 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 CSTB gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with CSTB 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 CSTB 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 CSTB gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of CSTB 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 CSTB from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.