KLK4 Gene: Kallikrein-Related Peptidase 4 - Function, Disease Associations, and Expression
A comprehensive biomedical overview of KLK4, including gene structure, protein function, tissue expression, mutations, and clinical significance.
Gene Information Card
| Symbol | KLK4 |
|---|---|
| Full Name | Kallikrein-related peptidase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.41 |
| NCBI Gene ID | 9622 ncbi.nlm.nih.gov/gene/9622 |
| Ensembl ID | ENSG00000167749 |
| UniProt ID | Q9Y5K2 |
| OMIM ID | 603767 |
| HGNC ID | 6368 |
| Aliases | EMSP1, PSTS, PRSS17, KLK-L1, MGC116878 |
Description
KLK4 (kallikrein-related peptidase 4) is a serine protease encoded by the KLK4 gene located on chromosome 19q13.41. It belongs to the kallikrein family of proteases, which are involved in diverse physiological processes including tissue remodeling, hormone processing, and enamel formation. KLK4 is primarily expressed in the prostate, skin, and developing teeth, where it plays a critical role in degrading enamel matrix proteins during maturation. Mutations in KLK4 cause autosomal recessive hypomaturation amelogenesis imperfecta, a disorder of tooth enamel development. Additionally, KLK4 has been implicated in cancer progression, particularly in prostate cancer, where it may contribute to tumor invasion and metastasis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Disease | Mechanism | Evidence |
| Amelogenesis imperfecta, hypomaturation type (AI) | Loss-of-function mutations in KLK4 lead to impaired degradation of enamel matrix proteins, resulting in defective enamel maturation. | ClinVar, OMIM (OMIM: 603767) |
| Prostate cancer | KLK4 is overexpressed in prostate cancer and may promote tumor invasion through extracellular matrix degradation and activation of growth factors. | COSMIC, literature (e.g., PMID: 14506261) |
| Ovarian cancer | Elevated KLK4 expression is associated with poor prognosis and may contribute to tumor progression via protease activity. | COSMIC, literature (e.g., PMID: 15604242) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Tissue | nTPM | Level |
| Prostate | High | High |
| Skin | Moderate | Moderate |
| Salivary gland | Low | Low |
| Kidney | Low | Low |
| Testis | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Cell Line | nTPM | Notes |
| LNCaP (prostate cancer) | High | Androgen-regulated expression |
| PC-3 (prostate cancer) | Moderate | Constitutive expression |
| MCF-7 (breast cancer) | Low | Minimal expression |
| HeLa (cervical cancer) | Low | Minimal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Variant | Type | Frequency | Effect |
| c.458C>T (p.Pro153Leu) | Missense | Rare (found in AI patients) | Loss of function; disrupts protease activity |
| c.694G>A (p.Gly232Arg) | Missense | Rare (found in AI patients) | Loss of function; affects protein stability |
| c.115delC (p.Leu39TrpfsTer26) | Frameshift | Rare (found in AI patients) | Loss of function; premature truncation |
| c.233A>G (p.Asn78Ser) | Missense | Rare (found in AI patients) | Loss of function; altered substrate binding |
Mutation functional classification
Loss of Function (LOF)
Mutations in KLK4 that reduce or abolish protease activity lead to hypomaturation amelogenesis imperfecta, characterized by defective enamel. These include missense, frameshift, and nonsense variants that impair protein function or stability.
Gain of Function (GOF)
No clear gain-of-function mutations have been reported for KLK4. Overexpression in cancers is due to transcriptional upregulation rather than activating mutations.
Dominant Negative (DN)
No dominant-negative effects have been described for KLK4 mutations; the disease is inherited in an autosomal recessive manner.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity | • proteolysis |
| • extracellular matrix disassembly | • enamel mineralization |
| • peptidase activity | • extracellular space |
| • secretory granule |
Pathways
• Kallikrein-kinin system
• Prostate cancer pathway (via ECM degradation)
• Enamel formation and maturation
Protein Summary
KLK4 is a secreted serine protease of the kallikrein family. It is synthesized as a preproenzyme and activated by proteolytic cleavage. The mature enzyme is involved in degrading enamel matrix proteins such as amelogenin, enabling proper enamel hardening. In addition, KLK4 is expressed in the prostate and skin, where it may participate in tissue remodeling and cell signaling. Its dysregulation is linked to cancer progression, particularly in prostate and ovarian cancers, where it can facilitate invasion and metastasis. The protein structure includes a catalytic triad (His, Asp, Ser) typical of serine proteases, and it is inhibited by serpins.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLK4 Knockout HEK293 Cell Line | EDJ-KQ6661 | Human | 9622 | Details Get a Quote |
| KLK4 Knockout HeLa Cell Line | EDJ-KQ55207 | Human | 9622 | Details Get a Quote |
| KLK4 Knockout A-549 Cell Line | EDJ-KQ63689 | Human | 9622 | Details Get a Quote |
| KLK4 Knockout HCT 116 Cell Line | EDJ-KQ72152 | Human | 9622 | Details Get a Quote |
