CST6 Gene (Cystatin E/M)
A cysteine protease inhibitor involved in tumor suppression and epithelial differentiation
Gene Information Card
| Symbol | CST6 |
|---|---|
| Full Name | Cystatin E/M |
| Gene Type | Protein coding |
| Chromosomal Location | 11q13.1 |
| NCBI Gene ID | 1474 ncbi.nlm.nih.gov/gene/1474 |
| Ensembl ID | ENSG00000175309 |
| UniProt ID | Q15828 |
| OMIM ID | 601891 |
| HGNC ID | 2478 |
| Aliases | CST6, cystatin E/M, cystatin-6, MGC12688 |
Description
CST6 encodes cystatin E/M, a member of the type 2 cystatin family of cysteine protease inhibitors. It inhibits papain-like cysteine proteases such as cathepsins B, L, and V. CST6 is frequently downregulated in metastatic breast cancer and other cancers, suggesting a tumor suppressor role. It is also involved in epidermal differentiation and hair follicle development.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer (metastatic) | Loss of CST6 expression leads to increased cathepsin activity, promoting invasion and metastasis. | PMID: 15126328, 17938252 |
| Melanoma | Epigenetic silencing of CST6 correlates with tumor progression and poor prognosis. | PMID: 20081839 |
| Prostate cancer | Reduced CST6 expression associated with aggressive disease and metastasis. | PMID: 21804531 |
| Ichthyosis (harlequin ichthyosis) | CST6 mutations cause defective epidermal barrier and abnormal keratinization. | PMID: 21983784 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 12.5 | Medium |
| Breast | 8.3 | Low |
| Prostate | 6.1 | Low |
| Lung | 4.7 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 2.1 | Low expression |
| MDA-MB-231 (breast cancer) | 0.8 | Very low expression |
| HaCaT (keratinocyte) | 15.3 | High expression |
| A375 (melanoma) | 1.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2T>C (p.Met1?) | Missense | <0.01% | Loss of start codon, likely loss of function |
| c.68C>T (p.Pro23Leu) | Missense | <0.01% | Reduced inhibitory activity |
| c.256G>A (p.Gly86Arg) | Missense | <0.01% | Impaired folding and secretion |
Mutation functional classification
Loss of Function (LOF)
Most CST6 mutations in cancer result in loss of function via epigenetic silencing or missense changes that reduce protease inhibitory activity.
Gain of Function (GOF)
No gain-of-function mutations reported for CST6.
Dominant Negative (DN)
No dominant-negative mutations reported for CST6.
View complete mutation data：
Gene Ontology (GO)
| • cysteine-type endopeptidase inhibitor activity (GO:0004869) | • extracellular region (GO:0005576) |
| • extracellular space (GO:0005615) | • plasma membrane (GO:0005886) |
| • keratinization (GO:0031424) | • response to drug (GO:0042493) |
Pathways
• Cysteine protease inhibition (cathepsins B
• L
• V)
• Epithelial differentiation and barrier formation
Protein Summary
Cystatin E/M (UniProt Q15828) is a 149-amino acid secreted glycoprotein with a molecular weight of ~16.5 kDa. It contains a conserved cystatin domain and inhibits papain-like cysteine proteases, particularly cathepsins B, L, and V. The protein is expressed in skin, breast, and prostate epithelia, and its loss is associated with cancer metastasis and epidermal disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CST6 Knockout HEK293 Cell Line | EDJ-KQ4374 | Human | 1474 | Details Get a Quote |
| CST6 Knockout HCT 116 Cell Line | EDJ-KQ26884 | Human | 1474 | Details Get a Quote |
| CST6 Knockout HeLa Cell Line | EDJ-KQ53018 | Human | 1474 | Details Get a Quote |
| CST6 Knockout A-549 Cell Line | EDJ-KQ61483 | Human | 1474 | Details Get a Quote |
