KLK5 (Kallikrein Related Peptidase 5)
A serine protease involved in skin desquamation, cancer progression, and inflammatory disorders.
Gene Information Card
| Symbol | KLK5 |
|---|---|
| Full Name | Kallikrein Related Peptidase 5 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 25818 ncbi.nlm.nih.gov/gene/25818 |
| Ensembl ID | ENSG00000167748 |
| UniProt ID | Q9Y337 |
| OMIM ID | 605643 |
| HGNC ID | 6367 |
| Aliases | KLK-L2, KLKL2, SCTE |
Description
KLK5 encodes a serine protease of the kallikrein family, known as stratum corneum tryptic enzyme (SCTE). It is primarily expressed in the skin and plays a critical role in desquamation by degrading corneodesmosomes. KLK5 also participates in extracellular matrix remodeling, inflammation, and cancer progression. Dysregulation is linked to Netherton syndrome and various malignancies.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Netherton syndrome | Loss-of-function mutations in SPINK5 lead to unopposed KLK5 activity, causing excessive proteolysis of corneodesmosomes and skin barrier defects. | OMIM #256500; PMID: 15146477 |
| Prostate cancer | KLK5 is downregulated in prostate cancer; reduced expression correlates with poor prognosis and metastasis. | PMID: 15604234; COSMIC |
| Ovarian cancer | KLK5 overexpression is associated with aggressive tumor behavior and shorter overall survival. | PMID: 17018707; ClinVar |
| Breast cancer | KLK5 expression is altered in breast cancer subtypes; potential biomarker for hormone receptor status. | PMID: 17975022 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Skin | 48.2 | High |
| Esophagus | 12.5 | Medium |
| Prostate | 3.1 | Low |
| Ovary | 1.8 | Low |
| Breast | 0.9 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HaCaT (keratinocytes) | 52.0 | Endogenous high expression |
| MCF-7 (breast cancer) | 2.3 | Low expression |
| PC-3 (prostate cancer) | 1.1 | Low expression |
| OVCAR-3 (ovarian cancer) | 8.7 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.247C>T (p.Arg83Cys) | Missense | <0.01% | Reduced catalytic activity; reported in ClinVar |
| c.485G>A (p.Gly162Asp) | Missense | <0.01% | Unknown significance |
| c.697_698insA (p.Thr233Asnfs*12) | Frameshift | <0.01% | Loss of function; associated with Netherton syndrome |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations in KLK5 lead to truncated, non-functional protease; implicated in skin barrier defects.
Gain of Function (GOF)
Not well documented; overexpression in ovarian cancer may reflect transcriptional upregulation rather than activating mutations.
Dominant Negative (DN)
No evidence for dominant-negative effects in KLK5.
View complete mutation data：
Gene Ontology (GO)
Pathways
• KEGG: hsa04610 – Complement and coagulation cascades (indirect)
• Reactome: R-HSA-1474228 – Degradation of the extracellular matrix
• Reactome: R-HSA-6809371 – Formation of the cornified envelope
Protein Summary
KLK5 is a 293-amino acid serine protease with a trypsin-like specificity. It is synthesized as a preproenzyme and activated by proteolytic cleavage. The mature enzyme is secreted and localizes to the extracellular space, where it degrades corneodesmosomal cadherins (e.g., DSG1, DSC1) to facilitate skin shedding. KLK5 activity is tightly regulated by SPINK5 (LEKTI). In cancer, KLK5 modulates tumor microenvironment via ECM degradation and activation of protease-activated receptors (PARs).
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLK5 Knockout HEK293 Cell Line | EDJ-KQ8245 | Human | 25818 | Details Get a Quote |
| KLK5 Knockout HCT 116 Cell Line | EDJ-KQ34170 | Human | 25818 | Details Get a Quote |
| KLK5 Knockout HeLa Cell Line | EDJ-KQ55822 | Human | 25818 | Details Get a Quote |
| KLK5 Knockout A-549 Cell Line | EDJ-KQ64313 | Human | 25818 | Details Get a Quote |
