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CST3 cystatin C [ Homo sapiens (human) ]

Gene ID: 1471, updated on 2-Nov-2024

Summary

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Official Symbol
CST3provided by HGNC
Official Full Name
cystatin Cprovided by HGNC
Primary source
HGNC:HGNC:2475
See related
Ensembl:ENSG00000101439 MIM:604312; AllianceGenome:HGNC:2475
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ARMD11; HEL-S-2
Summary
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]
Expression
Ubiquitous expression in brain (RPKM 148.6), salivary gland (RPKM 118.0) and 25 other tissues See more
Orthologs
all
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Genomic context

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See CST3 in Genome Data Viewer
Location:
20p11.21
Exon count:
4
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 20 NC_000020.11 (23626706..23637955, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 20 NC_060944.1 (23686282..23697531, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 20 NC_000020.10 (23607343..23618592, complement)

Chromosome 20 - NC_000020.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr20:23570170-23570774 Neighboring gene cystatin 9-like pseudogene 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:23583003-23583504 Neighboring gene cystatin 9 Neighboring gene ReSE screen-validated silencer GRCh37_chr20:23603438-23603648 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12733 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 12734 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 17643 Neighboring gene uncharacterized LOC124904965 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr20:23638069-23638568 Neighboring gene uncharacterized LOC107985383

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The application of serum cystatin C in estimating the renal function in women with preeclampsia. Guo HX, et al. Reprod Sci, 2012 Jul. PMID 22669102
  2. Comparing cystatin C changes as a measure of renal function before and after radiotherapy in patients with stomach cancer. Rasouli HA, et al. Acta Med Iran, 2012. PMID 22267378
  3. Serum cystatin C as a predictor for cardiovascular events in end-stage renal disease patients at the initiation of dialysis. Shin MJ, et al. Clin Exp Nephrol, 2012 Jun. PMID 22278599
  4. Probucol for the prevention of cystatin C-based contrast-induced acute kidney injury following primary or urgent angioplasty: a randomized, controlled trial. Yin L, et al. Int J Cardiol, 2013 Jul 31. PMID 22305809
  5. Cystatin C is associated with risk of venous thromboembolism in subjects with normal kidney function--the Tromsø study. Brodin EE, et al. Haematologica, 2012 Jul. PMID 22315498, Free PMC Article

See all (646) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.
    Title: Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.
  2. Monomer-Dimer Equilibrium of Human Cystatin C During Internalization Into Cancer Cells.
    Title: Monomer-Dimer Equilibrium of Human Cystatin C During Internalization Into Cancer Cells.
  3. CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.
    Title: CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.
  4. Cystatin C: immunoregulation role in macrophages infected with Porphyromonas gingivalis.
    Title: Cystatin C: immunoregulation role in macrophages infected with Porphyromonas gingivalis.
  5. Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity.
    Title: Modification of Association of Cystatin C With Kidney and Cardiovascular Outcomes by Obesity.
  6. Cystatin C and eGFRCKD-EPI-CysC: novel biomarkers for renal impairment diagnosis and two-year progression-free survival in multiple myeloma.
    Title: Cystatin C and eGFR(CKD-EPI-CysC): novel biomarkers for renal impairment diagnosis and two-year progression-free survival in multiple myeloma.
  7. Human cystatin C induces the disaggregation process of selected amyloid beta peptides: a structural and kinetic view.
    Title: Human cystatin C induces the disaggregation process of selected amyloid beta peptides: a structural and kinetic view.
  8. Serum Cystatin C is a potential biomarker for predicting amyotrophic lateral sclerosis survival.
    Title: Serum Cystatin C is a potential biomarker for predicting amyotrophic lateral sclerosis survival.
  9. Serum cystatin C for risk stratification of prediabetes and diabetes populations.
    Title: Serum cystatin C for risk stratification of prediabetes and diabetes populations.
  10. Determination of cystatin C reference interval for children in Croatia.
    Title: Determination of cystatin C reference interval for children in Croatia.
Submit: New GeneRIF Correction See all GeneRIFs (566)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Age related macular degeneration 11
MedGen: C2677774 OMIM: 611953 GeneReviews: Not available
not available
Hereditary cerebral amyloid angiopathy, Icelandic type
MedGen: C1527338 OMIM: 105150 GeneReviews: Not available
not available

EBI GWAS Catalog

Description
A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study.
EBI GWAS Catalog
New loci associated with kidney function and chronic kidney disease.
EBI GWAS Catalog
Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet inhibition and patient Outcomes study.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
HIV-1 infection increases cathepsin B, cystatin B, and cystatin C in the frontal white matter of patients with HIV-Associated Neurocognitive Disorders PubMed
HIV-1 infection upregulates CST3 in CHME-5 cells PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 interacts with CST3 PubMed
capsid gag HIV-1 capsid interacts with CST3 PubMed
integrase gag-pol HIV-1 integrase interacts with CST3 PubMed
retropepsin gag-pol HIV-1 protease activity is inhibited by CST3 PubMed
gag-pol HIV-1 protease interacts with CST3 PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC117328

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables amyloid-beta binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables cysteine-type endopeptidase inhibitor activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables cysteine-type endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables endopeptidase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables peptidase inhibitor activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protease binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in defense response IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of blood vessel remodeling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of collagen catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of elastin catabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of extracellular matrix disassembly IC
Inferred by Curator
more info
 PubMed 
involved_in negative regulation of extracellular matrix disassembly IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in negative regulation of peptidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of proteolysis IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of tissue remodeling IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in supramolecular fiber organization IGI
Inferred from Genetic Interaction
more info
 PubMed 
Component Evidence Code Pubs
located_in Golgi apparatus IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum TAS
Traceable Author Statement
more info
 PubMed 
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in extracellular exosome HDA PubMed 
located_in extracellular region IMP
Inferred from Mutant Phenotype
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
located_in extracellular space HDA PubMed 
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in extracellular space IDA
Inferred from Direct Assay
more info
 PubMed 
located_in ficolin-1-rich granule lumen TAS
Traceable Author Statement
more info
  
located_in plasma membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in tertiary granule lumen TAS
Traceable Author Statement
more info
  
is_active_in vesicle IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
cystatin-C
Names
bA218C14.4 (cystatin C)
cystatin 3
epididymis secretory protein Li 2
gamma-trace
neuroendocrine basic polypeptide
post-gamma-globulin

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_012887.3 RefSeqGene

    Range
    4983..9281
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_000099.4 → NP_000090.1  cystatin-C precursor

    See identical proteins and their annotated locations for NP_000090.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) differs in the 3' UTR compared to variant 2. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AL121894
    Consensus CDS
    CCDS13158.1
    UniProtKB/Swiss-Prot
    B2R5J9, D3DW42, P01034, Q6FGW9
    UniProtKB/TrEMBL
    A0A0K0K1J1
    Related
    ENSP00000366124.3, ENST00000376925.8
    Conserved Domains (1) summary
    smart00043
    Location:34 → 144
    CY; Cystatin-like domain

  2. NM_001288614.2 → NP_001275543.1  cystatin-C precursor

    See identical proteins and their annotated locations for NP_001275543.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) represents the longer variant. Variants 1 and 2 encode the same protein.
    Source sequence(s)
    AL121894
    Consensus CDS
    CCDS13158.1
    UniProtKB/Swiss-Prot
    B2R5J9, D3DW42, P01034, Q6FGW9
    UniProtKB/TrEMBL
    A0A0K0K1J1
    Related
    ENSP00000381448.1, ENST00000398411.5
    Conserved Domains (1) summary
    smart00043
    Location:34 → 144
    CY; Cystatin-like domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000020.11 Reference GRCh38.p14 Primary Assembly

    Range
    23626706..23637955 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060944.1 Alternate T2T-CHM13v2.0

    Range
    23686282..23697531 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P01034.1 GenPept UniProtKB/Swiss-Prot:P01034

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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