KLK4
Basic information
Region (hg38): 19:50906351-50911395
Previous symbols: [ "PRSS17" ]
Links
Phenotypes
GenCC
Source:
- amelogenesis imperfecta type 2A1 (Moderate), mode of inheritance: AR
- amelogenesis imperfecta type 2A1 (Strong), mode of inheritance: AR
- amelogenesis imperfecta type 2 (Supportive), mode of inheritance: AR
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Amelogenesis imperfecta, type IIA1 | AR | General | 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 | Dental | 15235027; 23355523 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (26 variants)
- not_provided (9 variants)
- Amelogenesis_imperfecta_type_2A1 (6 variants)
- KLK4-related_disorder (3 variants)
- Amelogenesis_imperfecta (2 variants)
- Male_infertility (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the KLK4 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004917.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | |||||
| missense | 26 | 30 | ||||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 4 | 3 | 26 | 4 | 3 |
Highest pathogenic variant AF is 0.000110886
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| KLK4 | protein_coding | protein_coding | ENST00000324041 | 5 | 4387 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00000454 | 0.412 | 125695 | 1 | 52 | 125748 | 0.000211 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.0312 | 147 | 148 | 0.993 | 0.00000927 | 1645 |
| Missense in 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 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00205 | 0.00199 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000217 | 0.000217 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000705 | 0.0000703 |
| Middle Eastern | 0.000217 | 0.000217 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.000489 | 0.000489 |
dbNSFP
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.;
- Pathway
- Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling
(Consensus)
Intolerance Scores
- loftool
- 0.252
- rvis_EVS
- 0.48
- rvis_percentile_EVS
- 79.25
Haploinsufficiency Scores
- pHI
- 0.105
- hipred
- N
- hipred_score
- 0.220
- ghis
- 0.417
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.0415
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Klk4
- Phenotype
- skeleton phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); craniofacial phenotype; growth/size/body region phenotype;
Gene ontology
- Biological process
- proteolysis;extracellular matrix disassembly;biomineral tissue development;amelogenesis
- Cellular component
- extracellular region;secretory granule
- Molecular function
- serine-type endopeptidase activity;protein binding;serine-type peptidase activity;metal ion binding