CST6 cystatin E/M [Homo sapiens (human)] - Gene

Summary

Official Symbol: CST6provided by HGNC
Official Full Name: cystatin E/Mprovided by HGNC
Primary source: HGNC:HGNC:2478
See related: Ensembl:ENSG00000175315 MIM:601891; AllianceGenome:HGNC:2478
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: ECTD15
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. This gene encodes a cystatin from the type 2 family, which is down-regulated in metastatic breast tumor cells as compared to primary tumor cells. Loss of expression is likely associated with the progression of a primary tumor to a metastatic phenotype. [provided by RefSeq, Jul 2008]
Expression: Biased expression in skin (RPKM 70.4) and lung (RPKM 4.9) See more
Orthologs: mouse all
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Genomic context

Location:: 11q13.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (66012008..66013505)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (66006130..66007628)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (65779479..65780976)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation.
Title: CST6 suppresses osteolytic bone disease in multiple myeloma by blocking osteoclast differentiation.
CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis.
Title: CST6 protein and peptides inhibit breast cancer bone metastasis by suppressing CTSB activity and osteoclastogenesis.
a loss-of-function variant in the human CST6 gene, which causes a novel autosomal recessive hypotrichosis syndrome
Title: Deficiency of the human cysteine protease inhibitor cystatin M/E causes hypotrichosis and dry skin.
High CST6 expression is associated with lymph-node metastasis in Triple-Negative Breast Cancer.
Title: Correlation of Cystatin E/M with Clinicopathological Features and Prognosis in Triple-Negative Breast Cancer.
Data suggest that melanoma cells internalize/absorb cystatin C from culture media, leading to increased intracellular cystatin C levels; cystatin E/M is internalized as well but at modest rate due to down-regulation of cell migration; however, the effect of intracellular cystatin E/M on down-regulation of legumain activity is pronounced.
Title: Low-level internalization of cystatin E/M affects legumain activity and migration of melanoma cells.
Results provide evidence that cystatin E/M is a tumor suppressor gene which plays an important role in the regulation of NF-kappaB.
Title: Cystatin E/M Suppresses Tumor Cell Growth through Cytoplasmic Retention of NF-κB.
Low CST6 expression is associated with breast cancer.
Title: TBX2 represses CST6 resulting in uncontrolled legumain activity to sustain breast cancer proliferation: a novel cancer-selective target pathway with therapeutic opportunities.
Developed a Methylation-Sensitive High Resolution Melting Analysis (MS-HRMA) assay for the investigation of CST6 promoter methylation in breast cancer patients.CST6 promoter was methylated in 39/80 of FFPEs.
Title: A closed-tube methylation-sensitive high resolution melting assay (MS-HRMA) for the semi-quantitative determination of CST6 promoter methylation in clinical samples.
The CST6 promoter is highly methylated in circulating cell-free DNA of breast cancer patients, but not in healthy individuals.
Title: CST6 promoter methylation in circulating cell-free DNA of breast cancer patients.
Data show a regulatory role of cystatin E/M in controlling both intra- and extracellular legumain activity.
Title: Intra- and extracellular regulation of activity and processing of legumain by cystatin E/M.

Submit: New GeneRIF Correction See all GeneRIFs (31)

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
Ectodermal dysplasia 15, hypohidrotic/hair type MedGen: C5193145 OMIM: 618535 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association study identifies three novel susceptibility loci for severe Acne vulgaris. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables cysteine-type endopeptidase inhibitor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in anatomical structure morphogenesis	TAS Traceable Author Statement more info	PubMed
involved_in epidermis development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of peptidase activity	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in cornified envelope	IEA Inferred from Electronic Annotation more info
located_in extracellular exosome	HDA more info	PubMed

General protein information

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Preferred Names: cystatin-M

Names: cystatin 6; cystatin M/E; cystatin-E; cysteine proteinase inhibitor

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.

mRNA and Protein(s)

NM_001323.4 → NP_001314.1 cystatin-M precursor

Status: REVIEWED

Source sequence(s)

AA778147, AI127639, U81233

Consensus CDS

CCDS8126.1

UniProtKB/Swiss-Prot

Q15828, Q540N7

UniProtKB/TrEMBL

Q6IBD2

Related

ENSP00000311313.2, ENST00000312134.3

Conserved Domains (1) summary

smart00043
Location:33 → 147

CY; Cystatin-like domain