KLK2
protein-codingkallikrein related peptidase 2, the group of Kallikreins
Gene summary
This gene encodes a member of the grandular kallikrein protein family. Kallikreins are a subgroup of serine proteases that are clustered on chromosome 19. Members of this family are involved in a diverse array of biological functions. The protein encoded by this gene is a highly active trypsin-like serine protease that selectively cleaves at arginine residues. This protein is primarily expressed in prostatic tissue and is responsible for cleaving pro-prostate-specific antigen into its enzymatically active form. This gene is highly expressed in prostate tumor cells and may be a prognostic maker for prostate cancer risk. Alternate splicing results in both coding and non-coding transcript variants. [provided by RefSeq, Jan 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~19.0 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 KLK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005551.5. 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 | 0 | |||||
| missense | 43 | 4 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 43 | 4 | 0 | 47 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005542.1 | 5 | MANE Select | |
| Ensembl | ENSP00000313581.2 | 5 | MANE Select | |
| RefSeq | NP_001002231.1 | 5 | Standard | |
| RefSeq | NP_001243009.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Renin-angiotensin system - Homo sapiens (human)
- Endocrine and other factor-regulated calcium reabsorption - Homo sapiens (human)
- Androgen Receptor Network in Prostate Cancer
- Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
- Signal Transduction
Biological Process
- regulation of systemic arterial blood pressure
- extracellular matrix disassembly
- zymogen activation
Molecular Function
- serine-type endopeptidase activity
Cellular Component
- extracellular region
- secretory granule
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000325321
- Coding exons
- 5
- Length
- 19000
- Individuals with no LoFs
- 125699
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 48
- Defined
- 125747
- p
- 0.000191
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.117 | 143 | 147 | 0.973 | 0.00000747 | 1690 |
| Missense (PolyPhen) | 42 | 49.289 | 0.85212 | 612 | ||
| Synonymous | 0.762 | 50 | 57.3 | 0.872 | 0.00000295 | 527 |
| Loss of Function | 0.782 | 7 | 9.62 | 0.728 | 4.10e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000058 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00076 | 0.00076 | rare |
| Finnish | 0.000046 | 0.000046 | rare |
| European (Non-Finnish) | 0.00025 | 0.00025 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0.00033 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Glandular kallikreins cleave Met-Lys and Arg-Ser bonds in kininogen to release Lys-bradykinin.;
Intolerance Scores
- LoFtool
- 0.281
- RVIS EVS
- 0.55
- RVIS percentile EVS
- 81.48
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0320
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |