KLK3 (PSA): Prostate-Specific Antigen Gene - Function, Disease Associations, and Clinical Significance
Comprehensive biomedical overview of the KLK3 gene encoding prostate-specific antigen (PSA), including genomic context, expression patterns, disease links, and mutation data.
Gene Information Card
| Symbol | KLK3 |
|---|---|
| Full Name | Kallikrein-related peptidase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 19q13.33 |
| NCBI Gene ID | 354 ncbi.nlm.nih.gov/gene/354 |
| Ensembl ID | ENSG00000142515 |
| UniProt ID | P07288 |
| OMIM ID | 176820 |
| HGNC ID | 6364 |
| Aliases | PSA, APS, KLK2A1, hK3, seminin |
Description
KLK3 (kallikrein-related peptidase 3) encodes prostate-specific antigen (PSA), a serine protease primarily produced by the prostate epithelium. PSA is the most widely used clinical biomarker for prostate cancer screening, diagnosis, and monitoring. The protein is secreted into seminal plasma where it liquefies the semen coagulum. KLK3 expression is regulated by androgens and is highly tissue-specific, with minimal expression outside the prostate. Clinically, elevated serum PSA levels correlate with prostate pathology including benign prostatic hyperplasia (BPH), prostatitis, and prostate cancer. The gene is part of the kallikrein gene cluster on chromosome 19.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer | Elevated KLK3 expression and serum PSA levels are used as a tumor marker. Somatic mutations and altered regulation contribute to cancer progression, though PSA itself is not oncogenic. | ClinVar, COSMIC, NCBI |
| Benign prostatic hyperplasia (BPH) | Non-malignant proliferation of prostate tissue leads to increased PSA production and elevated serum levels. | NCBI, OMIM |
| Prostatitis | Inflammation of the prostate causes disruption of the epithelial barrier, leading to elevated serum PSA. | NCBI |
| Metastatic prostate cancer | High KLK3 expression in metastatic lesions; PSA is used to monitor treatment response and disease progression. | COSMIC, ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prostate | nTPM: 1000+ | High |
| Seminal vesicle | nTPM: 5 | Low |
| Testis | nTPM: 1 | Low |
| Other tissues | nTPM: <1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| LNCaP | nTPM: 1000+ | Prostate cancer cell line; androgen-responsive; high KLK3 expression |
| PC-3 | nTPM: 1 | Prostate cancer cell line; androgen-independent; low KLK3 expression |
| DU145 | nTPM: 1 | Prostate cancer cell line; androgen-independent; low KLK3 expression |
| 22Rv1 | nTPM: 500 | Prostate cancer cell line; androgen-responsive; moderate KLK3 expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.178G>A (p.Asp60Asn) | Missense | Rare | Reduced enzymatic activity; clinical significance uncertain |
| c.433G>A (p.Val145Met) | Missense | Rare | Altered protein stability; reported in prostate cancer cases |
| c.560C>T (p.Thr187Met) | Missense | Rare | Potential effect on PSA secretion; observed in hereditary prostate cancer |
| c.−158G>A (promoter) | Regulatory | Common | May affect androgen response element binding; associated with altered PSA levels |
Mutation functional classification
Loss of Function (LOF)
Rare missense variants (e.g., p.Asp60Asn) that reduce proteolytic activity or impair protein folding/secretion.
Gain of Function (GOF)
Not well characterized; no clear gain-of-function mutations reported in KLK3.
Dominant Negative (DN)
No evidence for dominant-negative effects; KLK3 is a secreted protease, and mutations are typically recessive or neutral.
View complete mutation data：
Gene Ontology (GO)
| • serine-type endopeptidase activity | • peptidase activity |
| • protein binding | • extracellular space |
| • extracellular region | • proteolysis |
| • regulation of cell growth | • negative regulation of angiogenesis |
Pathways
• Kallikrein-kinin system
• Prostate cancer pathway
• Proteolysis
• Androgen receptor signaling pathway
Protein Summary
Prostate-specific antigen (PSA) is a 261-amino-acid glycoprotein synthesized as a preproenzyme. After cleavage of the signal peptide and pro-peptide, the mature active enzyme (237 amino acids) is secreted. PSA is a chymotrypsin-like serine protease that cleaves semenogelin I and II in seminal coagulum, facilitating sperm motility. In serum, PSA exists in free and complexed forms (bound to alpha-1-antichymotrypsin). The protein has a single catalytic triad (His57, Asp102, Ser195) and is stabilized by five disulfide bonds. PSA is used clinically as a biomarker; its half-life in serum is approximately 2-3 days.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| KLK3 Knockout HEK293 Cell Line | EDJ-KQ1939 | Human | 354 | Details Get a Quote |
| KLK3 Knockout HeLa Cell Line | EDJ-KQ52641 | Human | 354 | Details Get a Quote |
| KLK3 Knockout A-549 Cell Line | EDJ-KQ61114 | Human | 354 | Details Get a Quote |
| KLK3 Knockout HCT 116 Cell Line | EDJ-KQ69602 | Human | 354 | Details Get a Quote |
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