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 cysta... See more...

Aliases for CST3 Gene

Aliases for CST3 Gene

  • Cystatin C 2 3 5
  • Neuroendocrine Basic Polypeptide 3 4
  • Post-Gamma-Globulin 3 4
  • Gamma-Trace 3 4
  • Cystatin-C 3 4
  • Cystatin C (Amyloid Angiopathy And Cerebral Hemorrhage) 2
  • Epididymis Secretory Protein Li 2 3
  • BA218C14.4 (Cystatin C) 3
  • Cystatin 3 3
  • Cystatin-3 4
  • HEL-S-2 3
  • ARMD11 3

External Ids for CST3 Gene

Previous GeneCards Identifiers for CST3 Gene

  • GC20M023602
  • GC20M023609
  • GC20M023562

Summaries for CST3 Gene

Entrez Gene Summary for CST3 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 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 the most abundant extracellular inhibitor of cysteine proteases, which is found in high concentrations in biological fluids and is expressed in virtually all organs of the body. A mutation in this gene has been associated with amyloid angiopathy. Expression of this protein in vascular wall smooth muscle cells is severely reduced in both atherosclerotic and aneurysmal aortic lesions, establishing its role in vascular disease. In addition, this protein has been shown to have an antimicrobial function, inhibiting the replication of herpes simplex virus. Alternative splicing results in multiple transcript variants encoding a single protein. [provided by RefSeq, Nov 2014]

GeneCards Summary for CST3 Gene

CST3 (Cystatin C) is a Protein Coding gene. Diseases associated with CST3 include Cerebral Amyloid Angiopathy, Cst3-Related and Macular Degeneration, Age-Related, 11. Among its related pathways are Innate Immune System and Circadian rythm related genes. Gene Ontology (GO) annotations related to this gene include identical protein binding and endopeptidase inhibitor activity. An important paralog of this gene is CST2.

UniProtKB/Swiss-Prot Summary for CST3 Gene

  • As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.

Gene Wiki entry for CST3 Gene

Additional gene information for CST3 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CST3 Gene

Genomics for CST3 Gene

GeneHancer (GH) Regulatory Elements for CST3 Gene

Promoters and enhancers for CST3 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
GH20J023635 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 511.5 +1.6 1588 3.8 HNRNPK NRF1 POLR2G NCOR1 PHF8 ZFX ZIC2 POLR2A ZBTB11 ZBTB26 CST3 NXT1 ENSG00000270001
GH20J023602 Enhancer 0.6 Ensembl ENCODE 24.7 +35.9 35872 2.4 RFX1 SPI1 FOXA1 POLR2A MYC lnc-CST3-2 CST3 CSTL1 NAPB CST9 piR-61532-168
GH20J023628 Enhancer 1.1 ENCODE dbSUPER 13.3 +8.9 8883 2.3 EP300 FOXK2 POLR2G NCOR1 POLR2A KDM6A TCF7 ZBTB25 TGIF2 SKI NXT1 CST3 CST9 GZF1 ENSG00000270001 HSALNG0129271
GH20J023606 Enhancer 1 Ensembl ENCODE 14.4 +31.6 31572 1 EP300 ZNF217 CTCF REST ZBTB25 RAD21 TRIM22 TEAD1 ZKSCAN8 SMC3 CST9 HSALNG0129269 CST3 CSTL1 NAPB ENSG00000234832 NXT1 piR-40110-402
GH20J023620 Enhancer 0.8 Ensembl 15.9 +17.4 17373 0.6 KDM6A ZBTB25 SKI TEAD1 ZBTB26 ZKSCAN8 ZSCAN9 KMT2B FOXA2 KAT7 piR-59297-407 CST3 HSALNG0129271
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CST3 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CST3

Top Transcription factor binding sites by QIAGEN in the CST3 gene promoter:
  • AML1a
  • AP-1
  • C/EBPalpha
  • E47
  • GR
  • GR-alpha
  • GR-beta
  • MyoD
  • Tal-1beta
  • TGIF

Genomic Locations for CST3 Gene

Genomic Locations for CST3 Gene
chr20:23,626,706-23,638,473
(GRCh38/hg38)
Size:
11,768 bases
Orientation:
Minus strand
chr20:23,608,534-23,619,110
(GRCh37/hg19)
Size:
10,577 bases
Orientation:
Minus strand

Genomic View for CST3 Gene

Genes around CST3 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CST3 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CST3 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CST3 Gene

Proteins for CST3 Gene

  • Protein details for CST3 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P01034-CYTC_HUMAN
    Recommended name:
    Cystatin-C
    Protein Accession:
    P01034
    Secondary Accessions:
    • B2R5J9
    • D3DW42
    • Q6FGW9

    Protein attributes for CST3 Gene

    Size:
    146 amino acids
    Molecular mass:
    15799 Da
    Quaternary structure:
    • Homodimer.
    Miscellaneous:
    • Potential cerebrospinal fluid marker for the diagnosis of Creutzfeldt-Jakob disease.

    Three dimensional structures from OCA and Proteopedia for CST3 Gene

neXtProt entry for CST3 Gene

Post-translational modifications for CST3 Gene

  • The Thr-25 variant is O-glycosylated with a core 1 or possibly core 8 glycan. The signal peptide of the O-glycosylated Thr-25 variant is cleaved between Ala-20 and Val-21.
  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CST3 Gene

Antibody Products

Protein Products

No data available for DME Specific Peptides for CST3 Gene

Domains & Families for CST3 Gene

Gene Families for CST3 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Plasma proteins
  • Predicted secreted proteins

Protein Domains for CST3 Gene

Blocks:
  • Cysteine protease inhibitor
  • Proteinase inhibitor I25A and I25B, type 2 and phytocystatins
InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for CST3 Gene

GenScript: Design optimal peptide antigens:
  • Post-gamma-globulin (CYTC_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P01034

UniProtKB/Swiss-Prot:

CYTC_HUMAN :
  • Belongs to the cystatin family.
Family:
  • Belongs to the cystatin family.
genes like me logo Genes that share domains with CST3: view

Function for CST3 Gene

Molecular function for CST3 Gene

UniProtKB/Swiss-Prot Function:
As an inhibitor of cysteine proteinases, this protein is thought to serve an important physiological role as a local regulator of this enzyme activity.
GENATLAS Biochemistry:
cystatin C,cysteine proteinase inhibitor,found at high levels in saliva,tears,seminal plasma,type 2 family,expressed in all cellular types,inhibitor of cathepsin B

Phenotypes From GWAS Catalog for CST3 Gene

Gene Ontology (GO) - Molecular Function for CST3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001540 amyloid-beta binding IPI 18026102
GO:0002020 protease binding IPI 6203523
GO:0004866 endopeptidase inhibitor activity IDA 15127951
GO:0004869 cysteine-type endopeptidase inhibitor activity IDA 3488317
GO:0005515 protein binding IPI 15127951
genes like me logo Genes that share ontologies with CST3: view
genes like me logo Genes that share phenotypes with CST3: view

Human Phenotype Ontology for CST3 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CST3 Gene

MGI Knock Outs for CST3:
  • Cst3 Cst3<tm1Karl>
  • Cst3 Cst3<tm1b(EUCOMM)Wtsi>

Animal Model Products

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CST3

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for CST3 Gene

Localization for CST3 Gene

Subcellular locations from UniProtKB/Swiss-Prot for CST3 Gene

Secreted.

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 CST3 gene
Compartment Confidence
extracellular 5
plasma membrane 4
endoplasmic reticulum 4
golgi apparatus 4
cytosol 3
cytoskeleton 2
mitochondrion 2
nucleus 2
endosome 2
lysosome 2
peroxisome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (3)
  • Vesicles (3)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CST3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IMP,TAS --
GO:0005615 extracellular space IBA,IDA 3488317
GO:0005783 endoplasmic reticulum TAS 28904096
GO:0005788 endoplasmic reticulum lumen TAS --
GO:0005794 Golgi apparatus IDA 15212960
genes like me logo Genes that share ontologies with CST3: view

Pathways & Interactions for CST3 Gene

genes like me logo Genes that share pathways with CST3: view

Pathways by source for CST3 Gene

1 R&D Systems pathway for CST3 Gene
1 Cell Signaling Technology pathway for CST3 Gene

Gene Ontology (GO) - Biological Process for CST3 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006952 defense response IDA 6203523
GO:0010466 negative regulation of peptidase activity IDA 6203523
GO:0010711 negative regulation of collagen catabolic process IEP 10545518
GO:0010716 negative regulation of extracellular matrix disassembly IEP 10545518
GO:0010951 negative regulation of endopeptidase activity IEA --
genes like me logo Genes that share ontologies with CST3: view

No data available for SIGNOR curated interactions for CST3 Gene

Drugs & Compounds for CST3 Gene

(40) Drugs for CST3 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(33) Additional Compounds for CST3 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with CST3: view

Transcripts for CST3 Gene

mRNA/cDNA for CST3 Gene

2 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
3 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 CST3

Alternative Splicing Database (ASD) splice patterns (SP) for CST3 Gene

ExUns: 1 ^ 2a · 2b · 2c · 2d ^ 3 ^ 4a · 4b ^ 5a · 5b · 5c
SP1: - - - -
SP2: -
SP3: -
SP4:

Relevant External Links for CST3 Gene

GeneLoc Exon Structure for
CST3

Expression for CST3 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CST3 Gene

Protein differential expression in normal tissues from HIPED for CST3 Gene

This gene is overexpressed in Cerebrospinal fluid (49.9) and Vitreous humor (6.7).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CST3 Gene



Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CST3

SOURCE GeneReport for Unigene cluster for CST3 Gene:

Hs.304682

mRNA Expression by UniProt/SwissProt for CST3 Gene:

P01034-CYTC_HUMAN
Tissue specificity: Expressed in submandibular and sublingual saliva but not in parotid saliva (at protein level). Expressed in various body fluids, such as the cerebrospinal fluid and plasma. Expressed in highest levels in the epididymis, vas deferens, brain, thymus, and ovary and the lowest in the submandibular gland.

Evidence on tissue expression from TISSUES for CST3 Gene

  • Nervous system(5)
  • Blood(4.7)
  • Kidney(4.4)
  • Saliva(4.3)
  • Heart(3.9)
  • Muscle(3.9)
  • Liver(3.6)
  • Intestine(3.3)
  • Stomach(3.3)
  • Eye(3.2)
  • Urine(3.2)
  • Pancreas(3)
  • Lung(2.9)
  • Spleen(2.8)
  • Thyroid gland(2.8)
  • Lymph node(2.7)
  • Bone(2.5)
  • Gall bladder(2.5)
  • Skin(2.5)
  • Adrenal gland(2.3)
  • Bone marrow(2.1)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CST3 Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • cardiovascular
  • nervous
Regions:
Head and neck:
  • brain
  • eye
  • head
General:
  • blood
  • blood vessel
  • coagulation system
  • spinal cord
genes like me logo Genes that share expression patterns with CST3: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Protein tissue co-expression partners for CST3 Gene

Orthologs for CST3 Gene

This gene was present in the common ancestor of chordates.

Orthologs for CST3 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CST3 30
  • 89.87 (n)
dog
(Canis familiaris)
Mammalia LOC607874 30
  • 78.01 (n)
-- 31
  • 67 (a)
OneToMany
cow
(Bos Taurus)
Mammalia CST3 31 30
  • 75.6 (n)
OneToMany
rat
(Rattus norvegicus)
Mammalia Cst3 30
  • 73.66 (n)
mouse
(Mus musculus)
Mammalia Cst3 17 31 30
  • 71.69 (n)
oppossum
(Monodelphis domestica)
Mammalia -- 31
  • 48 (a)
OneToMany
platypus
(Ornithorhynchus anatinus)
Mammalia -- 31
  • 40 (a)
OneToMany
chicken
(Gallus gallus)
Aves CST3 30
  • 59.46 (n)
gga-mir-3526 31
  • 38 (a)
OneToMany
lizard
(Anolis carolinensis)
Reptilia -- 31
  • 42 (a)
OneToMany
tropical clawed frog
(Silurana tropicalis)
Amphibia LOC100485774 30
  • 48.33 (n)
zebrafish
(Danio rerio)
Actinopterygii cst3 31
  • 33 (a)
ManyToMany
Species where no ortholog for CST3 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)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for CST3 Gene

ENSEMBL:
Gene Tree for CST3 (if available)
TreeFam:
Gene Tree for CST3 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CST3: view image

Paralogs for CST3 Gene

Paralogs for CST3 Gene

(10) SIMAP similar genes for CST3 Gene using alignment to 1 proteins:

  • CYTC_HUMAN

Pseudogenes.org Pseudogenes for CST3 Gene

genes like me logo Genes that share paralogs with CST3: view

Variants for CST3 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CST3 Gene

SNP ID Clinical significance and condition Chr 20 pos Variation AA Info Type
714896 Benign: not provided 23,637,775(-) C/T MISSENSE_VARIANT
719121 Benign: not provided 23,637,628(-) G/T MISSENSE_VARIANT
728906 Benign: not provided 23,633,940(-) C/T SYNONYMOUS_VARIANT
746510 Likely Benign: not provided 23,637,830(-) C/G SYNONYMOUS_VARIANT
756159 Likely Benign: not provided 23,637,800(-) C/T SYNONYMOUS_VARIANT

Additional dbSNP identifiers (rs#s) for CST3 Gene

Structural Variations from Database of Genomic Variants (DGV) for CST3 Gene

Variant ID Type Subtype PubMed ID
esv3893322 CNV gain 25118596
nsv1071684 CNV deletion 25765185
nsv1118910 CNV deletion 24896259
nsv964381 CNV duplication 23825009

Variation tolerance for CST3 Gene

Gene Damage Index Score: 5.90; 74.29% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CST3 Gene

Human Gene Mutation Database (HGMD)
CST3
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CST3

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CST3 Gene

Disorders for CST3 Gene

MalaCards: The human disease database

(63) MalaCards diseases for CST3 Gene - From: UniProtKB/Swiss-Prot, OMIM, ClinVar, Orphanet, DISEASES, Novoseek, and GeneCards

Disorder Aliases PubMed IDs
cerebral amyloid angiopathy, cst3-related
  • amyloidosis, cerebroarterial, icelandic type
macular degeneration, age-related, 11
  • armd11
amyloidosis
  • amyloid disease
kidney disease
  • nephropathy
creutzfeldt-jakob disease
  • cjd
- elite association - COSMIC cancer census association via MalaCards
Search CST3 in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CYTC_HUMAN
  • Amyloidosis 6 (AMYL6) [MIM:105150]: A hereditary generalized amyloidosis due to cystatin C amyloid deposition. Cystatin C amyloid accumulates in the walls of arteries, arterioles, and sometimes capillaries and veins of the brain, and in various organs including lymphoid tissue, spleen, salivary glands, and seminal vesicles. Amyloid deposition in the cerebral vessels results in cerebral amyloid angiopathy, cerebral hemorrhage and premature stroke. Cystatin C levels in the cerebrospinal fluid are abnormally low. {ECO:0000269 PubMed:1352269, ECO:0000269 PubMed:2541223}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Macular degeneration, age-related, 11 (ARMD11) [MIM:611953]: A form of age-related macular degeneration, a multifactorial eye disease and the most common cause of irreversible vision loss in the developed world. In most patients, the disease is manifest as ophthalmoscopically visible yellowish accumulations of protein and lipid that lie beneath the retinal pigment epithelium and within an elastin-containing structure known as Bruch membrane. {ECO:0000269 PubMed:11815350, ECO:0000269 PubMed:19838169, ECO:0000269 PubMed:2764935}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for CST3

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 CST3: view

No data available for Genatlas for CST3 Gene

Publications for CST3 Gene

  1. Association of blood pressure and genetic background with white matter lesions in patients with mild cognitive impairment. (PMID: 18511756) Galluzzi S … Frisoni GB (The journals of gerontology. Series A, Biological sciences and medical sciences 2008) 3 23 41 54
  2. Genotype and plasma concentration of cystatin C in patients with late-onset Alzheimer disease. (PMID: 17310123) Chuo LJ … Kuo YM (Dementia and geriatric cognitive disorders 2007) 3 23 41 54
  3. Cystatin C levels are decreased in acute myocardial infarction: effect of cystatin C G73A gene polymorphism on plasma levels. (PMID: 15882666) Noto D … Averna MR (International journal of cardiology 2005) 3 23 41 54
  4. CST3 genotype associated with exudative age related macular degeneration. (PMID: 11815350) Zurdel J … Richard G (The British journal of ophthalmology 2002) 3 4 41 54
  5. Human cystatin C, an amyloidogenic protein, dimerizes through three-dimensional domain swapping. (PMID: 11276250) Janowski R … Jaskolski M (Nature structural biology 2001) 3 4 23 54

Products for CST3 Gene

Sources for CST3 Gene