CST3 cystatin C [Homo sapiens (human)] - Gene

Summary

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

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_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.
Title: Dominant CST3 variants cause adult onset leukodystrophy without amyloid angiopathy.
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.
CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.
Title: CST3 alleviates retinal vascular leakage by regulating the Rap1 signaling pathway.
Cystatin C: immunoregulation role in macrophages infected with Porphyromonas gingivalis.
Title: Cystatin C: immunoregulation role in macrophages infected with Porphyromonas gingivalis.
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.
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.
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.
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.
Serum cystatin C for risk stratification of prediabetes and diabetes populations.
Title: Serum cystatin C for risk stratification of prediabetes and diabetes populations.
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	Compare labs
Hereditary cerebral amyloid angiopathy, Icelandic type MedGen: C1527338 OMIM: 105150 GeneReviews: Not available	Compare labs

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 EBI GWAS CatalogPubMed
New loci associated with kidney function and chronic kidney disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Polymorphism of the cystatin C gene in patients with acute coronary syndromes: Results from the PLATelet inhibition and patient Outcomes study. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

STS-AA037016 (e-PCR)
- UniSTS:71964

CST3 (e-PCR)
- UniSTS:480122

SHGC-5971 (e-PCR)
- UniSTS:25223

SHGC-11944 (e-PCR)
- UniSTS:8860

GDB:196339 (e-PCR)
- UniSTS:155831

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 more info	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 more info	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

NG_012887.3 RefSeqGene

Range

4983..9281

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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