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 ... See more...

Aliases for CSTB Gene

Aliases for CSTB Gene

  • Cystatin B 2 3 5
  • Liver Thiol Proteinase Inhibitor 3 4
  • Cystatin B (Stefin B) 2 3
  • Cystatin-B 3 4
  • CPI-B 3 4
  • STFB 3 4
  • CST6 3 4
  • Epididymis Secretory Sperm Binding Protein 3
  • Epilepsy, Progressive Myoclonic 1 2
  • Stefin-B 4
  • Stefin B 2
  • EPM1A 3
  • EPM1 3
  • PME 3
  • ULD 3

External Ids for CSTB Gene

Previous HGNC Symbols for CSTB Gene

  • EPM1
  • STFB

Previous GeneCards Identifiers for CSTB Gene

  • GC21M041703
  • GC21M044050
  • GC21M044018
  • GC21M045192
  • GC21M030562

Summaries for CSTB Gene

Entrez Gene Summary for CSTB Gene

  • 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]

GeneCards Summary for CSTB Gene

CSTB (Cystatin B) is a Protein Coding gene. Diseases associated with CSTB include Myoclonic Epilepsy Of Unverricht And Lundborg and Unverricht-Lundborg Syndrome. Among its related pathways are Innate Immune System. Gene Ontology (GO) annotations related to this gene include endopeptidase inhibitor activity. An important paralog of this gene is CSTA.

UniProtKB/Swiss-Prot Summary for CSTB Gene

  • This is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B.

Gene Wiki entry for CSTB Gene

Additional gene information for CSTB Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CSTB Gene

Genomics for CSTB Gene

GeneHancer (GH) Regulatory Elements for CSTB Gene

Promoters and enhancers for CSTB Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH21J043774 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 528.8 -0.7 -681 5.1 HNRNPK SIN3A NRF1 POLR2G USF1 GTF2E2 PHF8 JUND ZFX ZNF639 CSTB lnc-HSF2BP-3 piR-43105-407 WDR4 U2AF1 ENSG00000184441 RRP1B PKNOX1 ENSG00000233754 RRP1
GH21J043788 Promoter/Enhancer 2.1 EPDnew Ensembl ENCODE CraniofacialAtlas 22.2 -13.4 -13356 2.8 HNRNPK ZBTB40 ZNF217 EP300 CTCF SIN3A NRF1 MYC USF1 POLR2G RRP1 piR-43105-408 CSTB ENSG00000184441 CFAP410 AATBC lnc-PDXK-2
GH21J043782 Enhancer 1.3 FANTOM5 ENCODE dbSUPER 26 -6.6 -6625 1.7 EP300 POLR2G NCOR1 ZNF10 POLR2A TCF7 FOXA1 CUX1 ZBTB25 TGIF2 TMEM97P1 lnc-RRP1-1 CSTB RRP1 AATBC LOC105372825
GH21J043811 Promoter/Enhancer 1.3 Ensembl ENCODE 23.7 -35.2 -35237 2.6 ZNF217 CTCF POLR2G USF1 ZNF639 ZIC2 ZBTB10 ZNF423 ZNF623 GABPA WDR4 U2AF1 RRP1B ENSG00000184441 CSTB PWP2 PKNOX1 UBE2G2 TRAPPC10 ENSG00000213440
GH21J043804 Enhancer 1.1 Ensembl ENCODE 27.9 -29.5 -29498 4.7 RXRA ZBTB40 SIN3A POLR2G SP1 EP300 RELA MYC TRIM22 POLR2A CSTB RRP1 AATBC lnc-PDXK-2 piR-50437-422
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CSTB on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CSTB

Top Transcription factor binding sites by QIAGEN in the CSTB gene promoter:
  • AP-4
  • ATF
  • c-Myc
  • Max
  • SREBP-1a
  • SREBP-1b
  • USF-1
  • USF-1:USF-2
  • USF1
  • USF2

Genomic Locations for CSTB Gene

Genomic Locations for CSTB Gene
chr21:43,772,511-43,776,445
(GRCh38/hg38)
Size:
3,935 bases
Orientation:
Minus strand
chr21:45,192,393-45,196,326
(GRCh37/hg19)
Size:
3,934 bases
Orientation:
Minus strand

Genomic View for CSTB Gene

Genes around CSTB on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CSTB Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CSTB Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CSTB Gene

Proteins for CSTB Gene

  • Protein details for CSTB Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P04080-CYTB_HUMAN
    Recommended name:
    Cystatin-B
    Protein Accession:
    P04080

    Protein attributes for CSTB Gene

    Size:
    98 amino acids
    Molecular mass:
    11140 Da
    Quaternary structure:
    • Able to form dimers stabilized by noncovalent forces.

    Three dimensional structures from OCA and Proteopedia for CSTB Gene

neXtProt entry for CSTB Gene

Post-translational modifications for CSTB Gene

  • Ubiquitination at Lys39, Lys44, and Lys78
  • Modification sites at PhosphoSitePlus

Other Protein References for CSTB Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

No data available for DME Specific Peptides for CSTB Gene

Domains & Families for CSTB Gene

Gene Families for CSTB Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins
  • Transporters

Protein Domains for CSTB Gene

Blocks:
  • Cysteine protease inhibitor
  • Stefin A signature
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CSTB Gene

GenScript: Design optimal peptide antigens:
  • Stefin-B (CYTB_HUMAN)
  • cDNA, FLJ92415, Homo sapiens cystatin B (stefin B) (CSTB), mRNA (Q76LA1_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P04080

UniProtKB/Swiss-Prot:

CYTB_HUMAN :
  • Belongs to the cystatin family.
Family:
  • Belongs to the cystatin family.
genes like me logo Genes that share domains with CSTB: view

Function for CSTB Gene

Molecular function for CSTB Gene

UniProtKB/Swiss-Prot Function:
This is an intracellular thiol proteinase inhibitor. Tightly binding reversible inhibitor of cathepsins L, H and B.
GENATLAS Biochemistry:
cystatin B,cysteine proteinase inhibitor,type 2 family,widely expressed

Phenotypes From GWAS Catalog for CSTB Gene

Gene Ontology (GO) - Molecular Function for CSTB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002020 protease binding IPI 6203523
GO:0003723 RNA binding HDA 22658674
GO:0004866 endopeptidase inhibitor activity TAS,IEA 3053245
GO:0004869 cysteine-type endopeptidase inhibitor activity IDA,IEA 3488317
GO:0030414 peptidase inhibitor activity IEA --
genes like me logo Genes that share ontologies with CSTB: view
genes like me logo Genes that share phenotypes with CSTB: view

Human Phenotype Ontology for CSTB Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CSTB Gene

MGI Knock Outs for CSTB:
  • Cstb Cstb<tm1b(EUCOMM)Wtsi>
  • Cstb Cstb<tm1Rm>

Animal Model Products

CRISPR Products

miRNA for CSTB Gene

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CSTB

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CSTB Gene

Localization for CSTB Gene

Subcellular locations from UniProtKB/Swiss-Prot for CSTB Gene

Cytoplasm. Nucleus.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CSTB gene
Compartment Confidence
extracellular 5
nucleus 5
cytosol 5
plasma membrane 2
cytoskeleton 2
mitochondrion 2
endosome 2
lysosome 2
peroxisome 1
endoplasmic reticulum 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Cytosol (3)
  • Nucleoli (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CSTB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005615 extracellular space IDA 3488317
GO:0005622 intracellular IEA --
GO:0005634 nucleus IEA --
GO:0005730 nucleolus IDA --
genes like me logo Genes that share ontologies with CSTB: view

Pathways & Interactions for CSTB Gene

PathCards logo

SuperPathways for CSTB Gene

genes like me logo Genes that share pathways with CSTB: view

Pathways by source for CSTB Gene

3 Reactome pathways for CSTB Gene

Gene Ontology (GO) - Biological Process for CSTB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0008344 adult locomotory behavior IEA --
GO:0010466 negative regulation of peptidase activity IDA 6203523
GO:0010951 negative regulation of endopeptidase activity IEA --
GO:0043312 neutrophil degranulation TAS --
GO:0045861 negative regulation of proteolysis IDA 3488317
genes like me logo Genes that share ontologies with CSTB: view

No data available for SIGNOR curated interactions for CSTB Gene

Drugs & Compounds for CSTB Gene

(8) Drugs for CSTB Gene - From: DrugBank, ApexBio, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Cupric Chloride Approved, Investigational Pharma Target 0
Papain Inhibitor Pharma Inhibitor of peptidase activity of Papain 0

(3) Additional Compounds for CSTB Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs

(1) ApexBio Compounds for CSTB Gene

Compound Action Cas Number
Papain Inhibitor Inhibitor of peptidase activity of Papain 70195-20-9
genes like me logo Genes that share compounds with CSTB: view

Drug Products

Transcripts for CSTB Gene

mRNA/cDNA for CSTB Gene

1 REFSEQ mRNAs :
9 NCBI additional mRNA sequence :
4 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CSTB

Alternative Splicing Database (ASD) splice patterns (SP) for CSTB Gene

ExUns: 1a · 1b ^ 2 ^ 3a · 3b
SP1:
SP2:

Relevant External Links for CSTB Gene

GeneLoc Exon Structure for
CSTB

Expression for CSTB Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CSTB Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CSTB Gene

This gene is overexpressed in Esophagus - Mucosa (x24.9) and Vagina (x5.1).

Protein differential expression in normal tissues from HIPED for CSTB Gene

This gene is overexpressed in Esophagus (7.9), Oral epithelium (6.5), and Saliva (6.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CSTB Gene



Protein tissue co-expression partners for CSTB Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CSTB

SOURCE GeneReport for Unigene cluster for CSTB Gene:

Hs.695

Evidence on tissue expression from TISSUES for CSTB Gene

  • Liver(4.6)
  • Nervous system(3.9)
  • Lung(3.6)
  • Intestine(3.2)
  • Blood(2.6)
  • Pancreas(2.5)
  • Heart(2.3)
  • Muscle(2.3)
  • Kidney(2.2)
  • Skin(2.2)
  • Stomach(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CSTB Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • nervous
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • head
Limb:
  • foot
  • lower limb
General:
  • peripheral nerve
  • peripheral nervous system
genes like me logo Genes that share expression patterns with CSTB: view

No data available for mRNA Expression by UniProt/SwissProt for CSTB Gene

Orthologs for CSTB Gene

This gene was present in the common ancestor of chordates.

Orthologs for CSTB Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CSTB 31 30
  • 99.32 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CSTB 31 31 30
  • 81.29 (n)
OneToMany
-- 31
  • 60 (a)
OneToMany
dog
(Canis familiaris)
Mammalia CSTB 31
  • 79 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Cstb 30
  • 78.57 (n)
mouse
(Mus musculus)
Mammalia Cstb 17 31 30
  • 77.21 (n)
oppossum
(Monodelphis domestica)
Mammalia CSTB 31
  • 57 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CSTB 31
  • 22 (a)
OneToOne
chicken
(Gallus gallus)
Aves CSTB 31 30
  • 72.79 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CSTB 31
  • 59 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii zgc:56530 31 30
  • 57.82 (n)
ManyToMany
si:ch211-161h7.6 31
  • 53 (a)
ManyToMany
zgc:153129 31
  • 47 (a)
ManyToMany
Species where no ortholog for CSTB was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CSTB Gene

ENSEMBL:
Gene Tree for CSTB (if available)
TreeFam:
Gene Tree for CSTB (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CSTB: view image

Paralogs for CSTB Gene

Paralogs for CSTB Gene

(1) SIMAP similar genes for CSTB Gene using alignment to 2 proteins:

  • CYTB_HUMAN
  • Q76LA1_HUMAN

Pseudogenes.org Pseudogenes for CSTB Gene

genes like me logo Genes that share paralogs with CSTB: view

Variants for CSTB Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CSTB Gene

SNP ID Clinical significance and condition Chr 21 pos Variation AA Info Type
659184 Pathogenic: Progressive myoclonic epilepsy 43,774,295(-) T/TCGCA FRAMESHIFT_VARIANT
666012 Uncertain Significance: Progressive myoclonic epilepsy 43,774,278(-) G/A MISSENSE_VARIANT
670906 Benign: not provided 43,776,115(-) A/G INTRON_VARIANT
671988 Likely Benign: not provided 43,776,304(-) TCGGCGAGGGGACG/T FIVE_PRIME_UTR_VARIANT
677583 Likely Benign: not provided 43,776,096(-) A/G INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for CSTB Gene

Structural Variations from Database of Genomic Variants (DGV) for CSTB Gene

Variant ID Type Subtype PubMed ID
esv33817 CNV loss 17666407
nsv470904 CNV loss 18288195
nsv509799 CNV insertion 20534489
nsv520305 CNV loss 19592680
nsv834107 CNV loss 17160897
nsv834108 CNV loss 17160897
nsv953642 CNV deletion 24416366

Variation tolerance for CSTB Gene

Residual Variation Intolerance Score: 44.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.40; 8.69% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CSTB Gene

Human Gene Mutation Database (HGMD)
CSTB
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CSTB

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CSTB Gene

Disorders for CSTB Gene

MalaCards: The human disease database

(26) MalaCards diseases for CSTB Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
myoclonic epilepsy of unverricht and lundborg
  • uld
unverricht-lundborg syndrome
  • myoclonic epilepsy of unverricht and lundborg
lingual-facial-buccal dyskinesia
  • oro-facial dyskinesia
hypohidrotic ectodermal dysplasia autosomal recessive
  • anhidrotic ectodermal dysplasia, autosomal recessive
dystonia
  • dystonic disease
- elite association - COSMIC cancer census association via MalaCards
Search CSTB in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CYTB_HUMAN
  • Epilepsy, progressive myoclonic 1 (EPM1) [MIM:254800]: An autosomal recessive disorder characterized by severe, stimulus-sensitive myoclonus and tonic-clonic seizures. The onset, occurring between 6 and 13 years of age, is characterized by convulsions. Myoclonus begins 1 to 5 years later. The twitchings occur predominantly in the proximal muscles of the extremities and are bilaterally symmetrical, although asynchronous. At first small, they become late in the clinical course so violent that the victim is thrown to the floor. Mental deterioration and eventually dementia develop. {ECO:0000269 PubMed:9012407}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CSTB

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CSTB: view

No data available for Genatlas for CSTB Gene

Publications for CSTB Gene

  1. Mutations in the gene encoding cystatin B in progressive myoclonus epilepsy (EPM1) (PMID: 8596935) Pennacchio LA … Myers RM (Science (New York, N.Y.) 1996) 2 3 4 23 54
  2. Nuclear localization of cystatin B, the cathepsin inhibitor implicated in myoclonus epilepsy (EPM1). (PMID: 11139332) Riccio M … Santi S (Experimental cell research 2001) 3 4 23 54
  3. Identification of mutations in cystatin B, the gene responsible for the Unverricht-Lundborg type of progressive myoclonus epilepsy (EPM1). (PMID: 9012407) Lalioti MD … Antonarakis SE (American journal of human genetics 1997) 3 4 23 54
  4. The refined 2.4 A X-ray crystal structure of recombinant human stefin B in complex with the cysteine proteinase papain: a novel type of proteinase inhibitor interaction. (PMID: 2347312) Stubbs MT … Turk V (The EMBO journal 1990) 3 4 23 54
  5. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41 54

Products for CSTB Gene

Sources for CSTB Gene