KLK3
protein-codingkallikrein related peptidase 3, the group of Kallikreins
Gene summary
Kallikreins are a subgroup of serine proteases having diverse physiological functions. Growing evidence suggests that many kallikreins are implicated in carcinogenesis and some have potential as novel cancer and other disease biomarkers. The gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. It encodes a single-chain glycoprotein, a protease which is synthesized in the epithelial cells of the prostate gland, and is present in seminal plasma. It is thought to function normally in the liquefaction of seminal coagulum, presumably by hydrolysis of the high molecular mass seminal vesicle protein. The serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of prostatic carcinoma. Alternate splicing of this gene generates several transcript variants encoding different isoforms. [provided by RefSeq, Dec 2019]
- APS
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KLK3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001648.2. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 5 | 2 | 7 | |||
| missense | 38 | 5 | 3 | 46 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 39 | 10 | 5 | 54 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001639.1 | 5 | MANE Select | |
| Ensembl | ENSP00000314151.1 | 5 | MANE Select | |
| RefSeq | NP_001025218.1 | 5 | Standard | |
| RefSeq | NP_001025219.1 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prostate cancer - Homo sapiens (human)
- Pathways in cancer - Homo sapiens (human)
- Androgen receptor signaling pathway
- Androgen Receptor Network in Prostate Cancer
- Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
Biological Process
- antibacterial peptide production
- regulation of systemic arterial blood pressure
- proteolysis
- negative regulation of angiogenesis
- zymogen activation
Molecular Function
- endopeptidase activity
- serine-type endopeptidase activity
- protein binding
- serine-type peptidase activity
- hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides
Cellular Component
- extracellular region
- extracellular space
- nucleus
- secretory granule
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326003
- Coding exons
- 5
- Length
- 5850
- Individuals with no LoFs
- 125715
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 31
- Defined
- 125746
- p
- 0.000123
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.253 | 170 | 161 | 1.06 | 0.00000926 | 1682 |
| Missense (PolyPhen) | 60 | 56.816 | 1.056 | 640 | ||
| Synonymous | -1.63 | 84 | 67.0 | 1.25 | 0.00000429 | 539 |
| Loss of Function | 0.475 | 9 | 10.7 | 0.843 | 5.24e-7 | 103 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00012 | 0.00012 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00049 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.;
Recessive Scores
- pRec
- 0.410
Intolerance Scores
- LoFtool
- 0.0825
- RVIS EVS
- 0.2
- RVIS percentile EVS
- 67.36
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.528
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |