| HGNC Family | Kallikreins (KLK), Proteases, serine (PRSS) |
| Name | kallikrein-related peptidase 4 |
| Description | 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] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Kallikrein‐related peptidase 4 (KLK4) is a trypsin‐like serine protease with multifaceted functions that vary by tissue context. In prostate cancer, KLK4 expression is elevated in malignant glands compared to benign tissue, and its upregulation is linked to alterations in cellular behavior that include reduced growth rates, enhanced cell migration, and promotion of an epithelial–mesenchymal transition marked by loss of E‐cadherin expression. Moreover, KLK4 can signal via protease‐activated receptors – activating both PAR‐1 and PAR‐2 – to induce intracellular calcium fluxes that may further contribute to a proinvasive, metastatic phenotype."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its role in tumor progression, KLK4 plays a critical part in enamel biomineralization. During the maturation stage of enamel formation, KLK4 is expressed by ameloblasts to degrade enamel matrix proteins, a process essential for the proper growth, interlocking, and hardening of enamel crystals. Deficiency of KLK4 leads to retention of enamel proteins, resulting in structurally compromised enamel that is prone to rapid abrasion after tooth eruption."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifunctional nature of KLK4 – serving not only as a mediator of prostate cancer cell invasiveness through proteolytic and receptor‐mediated signaling but also as an indispensable factor in achieving mature, robust enamel. This duality highlights its potential as a target for both therapeutic intervention in prostate cancer and diagnostic evaluation of enamel biomineralization disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "T L Veveris-Lowe, M G Lawrence, R L Collard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kallikrein 4 (hK4) and prostate-specific antigen (PSA) are associated with the loss of E-cadherin and an epithelial-mesenchymal transition (EMT)-like effect in prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1677/erc.1.00958"}], "href": "https://doi.org/10.1677/erc.1.00958"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16172196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16172196"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Andrew J Ramsay, Ying Dong, Melanie L Hunt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Kallikrein-related peptidase 4 (KLK4) initiates intracellular signaling via protease-activated receptors (PARs). KLK4 and PAR-2 are co-expressed during prostate cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M709493200"}], "href": "https://doi.org/10.1074/jbc.M709493200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18308730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18308730"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "James P Simmer, Yuanyuan Hu, Rangsiyakorn Lertlam, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hypomaturation enamel defects in Klk4 knockout/LacZ knockin mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.013623"}], "href": "https://doi.org/10.1074/jbc.M109.013623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19578120"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19578120"}]}]}]}
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| Synonyms | KLK-L1, KALLIKREIN, AI2A1, PSTS, ARM1, EMSP1, PRSS17, EMSP |
| Proteins | KLK4_HUMAN |
| NCBI Gene ID | 9622 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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KLK4 has 2,824 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, functional term, phrase or reference, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 91 datasets.
Click the + buttons to view associations for KLK4 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Achilles Cell Line Gene Essentiality Profiles | cell lines with fitness changed by KLK4 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset. | |
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of KLK4 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset. | |
| Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray | tissue samples with high or low expression of KLK4 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of KLK4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset. | |
| BioGPS Human Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KLK4 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| BioGPS Mouse Cell Type and Tissue Gene Expression Profiles | cell types and tissues with high or low expression of KLK4 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLK4 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CCLE Cell Line Gene Expression Profiles | cell lines with high or low expression of KLK4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset. | |
| ChEA Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLK4 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of KLK4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset. | |
| ChEA Transcription Factor Targets 2022 | transcription factors binding the promoter of KLK4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| ClinVar Gene-Phenotype Associations | phenotypes associated with KLK4 gene from the curated ClinVar Gene-Phenotype Associations dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores | cellular components containing KLK4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing KLK4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores | cellular components co-occuring with KLK4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with KLK4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset. | |
| COSMIC Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLK4 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with KLK4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with KLK4 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with KLK4 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by KLK4 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DISEASES Curated Gene-Disease Association Evidence Scores | diseases involving KLK4 gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Curated Gene-Disease Association Evidence Scores 2025 | diseases involving KLK4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with KLK4 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores | diseases co-occuring with KLK4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with KLK4 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DisGeNET Gene-Disease Associations | diseases associated with KLK4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with KLK4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KLK4 gene from the ENCODE Histone Modification Site Profiles dataset. | |
| ENCODE Transcription Factor Binding Site Profiles | transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLK4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of KLK4 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| ESCAPE Omics Signatures of Genes and Proteins for Stem Cells | PubMedIDs of publications reporting gene signatures containing KLK4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset. | |
| GAD Gene-Disease Associations | diseases associated with KLK4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset. | |
| GAD High Level Gene-Disease Associations | diseases associated with KLK4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with KLK4 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset. | |
| GeneSigDB Published Gene Signatures | PubMedIDs of publications reporting gene signatures containing KLK4 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of KLK4 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KLK4 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of KLK4 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of KLK4 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of KLK4 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of KLK4 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving KLK4 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Biological Process Annotations 2023 | biological processes involving KLK4 gene from the curated GO Biological Process Annotations 2023 dataset. | |
| GO Biological Process Annotations 2025 | biological processes involving KLK4 gene from the curated GO Biological Process Annotations2025 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing KLK4 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by KLK4 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by KLK4 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by KLK4 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of KLK4 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles | tissues with high or low expression of KLK4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of KLK4 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of KLK4 gene relative to other tissue samples from the GTEx Tissue Sample Gene Expression Profiles dataset. | |
| GWASdb SNP-Phenotype Associations | phenotypes associated with KLK4 gene in GWAS datasets from the GWASdb SNP-Phenotype Associations dataset. | |
| Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles | cell lines with high or low expression of KLK4 gene relative to other cell lines from the Heiser et al., PNAS, 2011 Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of KLK4 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of KLK4 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of KLK4 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HPO Gene-Disease Associations | phenotypes associated with KLK4 gene by mapping known disease genes to disease phenotypes from the HPO Gene-Disease Associations dataset. | |
| HuBMAP Azimuth Cell Type Annotations | cell types associated with KLK4 gene from the HuBMAP Azimuth Cell Type Annotations dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with KLK4 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by KLK4 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for KLK4 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of KLK4 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of KLK4 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| KnockTF Gene Expression Profiles with Transcription Factor Perturbations | transcription factor perturbations changing expression of KLK4 gene from the KnockTF Gene Expression Profiles with Transcription Factor Perturbations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain KLK4 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by KLK4 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of KLK4 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MPO Gene-Phenotype Associations | phenotypes of transgenic mice caused by KLK4 gene mutations from the MPO Gene-Phenotype Associations dataset. | |
| OMIM Gene-Disease Associations | phenotypes associated with KLK4 gene from the curated OMIM Gene-Disease Associations dataset. | |
| Pathway Commons Protein-Protein Interactions | interacting proteins for KLK4 from the Pathway Commons Protein-Protein Interactions dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of KLK4 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving KLK4 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving KLK4 protein from the Wikipathways PFOCR 2024 dataset. | |
| PID Pathways | pathways involving KLK4 protein from the PID Pathways dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of KLK4 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at KLK4 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of KLK4 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of KLK4 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of KLK4 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of KLK4 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of KLK4 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of KLK4 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores | tissues with high expression of KLK4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KLK4 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores | tissues with high expression of KLK4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of KLK4 protein in proteomics datasets from the TISSUES Experimental Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores | tissues co-occuring with KLK4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with KLK4 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2024 | pathways involving KLK4 protein from the WikiPathways Pathways 2024 dataset. | |
