KLK4
protein-codingkallikrein related peptidase 4, the group of Kallikreins|Serine proteases
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. This gene is one of the fifteen kallikrein subfamily members located in a cluster on chromosome 19. In some tissues its expression is hormonally regulated. The expression pattern of a similar mouse protein in murine developing teeth supports a role for the protein in the degradation of enamel proteins. Several transcript variants encoding different proteins have been found for this gene. [provided by RefSeq, Dec 2014]
- PRSS17
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~5.0 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AR
Disease ID:MONDO:0008772
Submitter: PanelApp Australia
Inheritance Pattern: AR
Disease ID:MONDO:0008772
Submitter: Labcorp Genetics (formerly Invitae)
Inheritance Pattern: AR
Disease ID:MONDO:0008772
Submitter: Ambry Genetics
Inheritance Pattern: AR
Disease ID:MONDO:0015048
Submitter: Orphanet
Clinical Genomic Database (CGD)
Manifestation: Dental
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to KLK4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_004917.5. 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 | 2 | 2 | 4 | |||
| missense | 1 | 30 | 2 | 1 | 34 | |
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 4 | 3 | 30 | 4 | 3 | 44 |
Highest pathogenic variant AF is 0.000110886445
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_004908.4 | 5 | MANE Select | |
| Ensembl | ENSP00000326159.1 | 5 | MANE Select | |
| RefSeq | NP_001289890.1 | 3 | Standard | |
| Ensembl | ENSP00000399448.2 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
Biological Process
- proteolysis
- extracellular matrix disassembly
- biomineral tissue development
- amelogenesis
Molecular Function
- serine-type endopeptidase activity
- protein binding
- serine-type peptidase activity
- metal ion binding
Cellular Component
- extracellular region
- secretory granule
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000324041
- Coding exons
- 5
- Length
- 4387
- Individuals with no LoFs
- 125695
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 52
- Defined
- 125748
- p
- 0.000211
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0312 | 147 | 148 | 0.993 | 0.00000927 | 1645 |
| Missense (PolyPhen) | 65 | 62.431 | 1.0412 | 684 | ||
| Synonymous | -0.464 | 72 | 67.2 | 1.07 | 0.00000520 | 505 |
| Loss of Function | 0.484 | 9 | 10.7 | 0.840 | 4.80e-7 | 111 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0019 | 0.0018 | notable |
| Latino/Admixed American | 0.00014 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00022 | 0.00022 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000070 | 0.000070 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00049 | 0.00049 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has a major role in enamel formation (PubMed:15235027). Required during the maturation stage of tooth development for clearance of enamel proteins and normal structural patterning of the crystalline matrix (By similarity). {ECO:0000250|UniProtKB:Q9Z0M1, ECO:0000269|PubMed:15235027}.;
- Disease
- DISEASE: Amelogenesis imperfecta, hypomaturation type, 2A1 (AI2A1) [MIM:204700]: A defect of enamel formation. The disorder involves both primary and secondary dentitions. The teeth have a shiny agar jelly appearance and the enamel is softer than normal. Brown pigment is present in middle layers of enamel. {ECO:0000269|PubMed:15235027}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Intolerance Scores
- LoFtool
- 0.252
- RVIS EVS
- 0.48
- RVIS percentile EVS
- 79.25
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0415
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |