KLKB1 Gene

HGNC Family	Kallikreins (KLK)
Name	kallikrein B, plasma (Fletcher factor) 1
Description	This gene encodes a glycoprotein that participates in the surface-dependent activation of blood coagulation, fibrinolysis, kinin generation and inflammation. The encoded preproprotein present in plasma as a non-covalent complex with high molecular weight kininogen undergoes proteolytic processing mediated by activated coagulation factor XII to generate a disulfide-linked, heterodimeric serine protease comprised of heavy and light chains. Certain mutations in this gene cause prekallikrein deficiency. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The KLKB1 gene encodes plasma prekallikrein, a serine protease zymogen that plays a central role in the contact activation system. Upon appropriate stimulation on vascular or cell surfaces – for example, following binding to negatively charged macromolecules or activation by enzymes such as factor XIIa or prolylcarboxypeptidase (PRCP) – prekallikrein is converted into active plasma kallikrein. Kallikrein, in turn, proteolytically cleaves high–molecular weight kininogen to release bradykinin, a potent mediator that increases vascular permeability and promotes inflammation, as observed in conditions such as hereditary angioedema [(1,6)]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its proinflammatory role, kallikrein participates in coagulation and fibrinolysis. Genetic variations within the KLKB1 locus have been associated with altered plasma factor XI levels and an increased risk of deep vein thrombosis, indicating that KLKB1 activity modulates thrombotic risk [(2,8)]. Moreover, experimental reduction of prekallikrein levels yields an antithrombotic phenotype without impairing normal hemostasis [(3)], while its proteolytic activity has also been implicated in plasmin generation during wound healing processes [(4)]."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n The activation and function of plasma kallikrein are tightly regulated by endogenous inhibitors such as C1 inhibitor and by cross‐talk with other protease cascades. For instance, the activity of kallikrein is modulated by its interactions with PRCP on endothelial cells, and its action is countered by inhibitors to prevent excessive bradykinin generation [(5,7)]. Collectively, these studies underscore that the KLKB1 gene product is a pivotal mediator at the intersection of inflammation, coagulation, and tissue repair, making it a compelling target for therapeutic intervention in diseases ranging from angioedema and thrombosis to impaired wound healing.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n "}, {"type": "b", "children": [{"type": "t", "text": "References:"}]}, {"type": "t", "text": "<br>."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eun D Han, Ryan C MacFarlane, Aideen N Mulligan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Increased vascular permeability in C1 inhibitor-deficient mice mediated by the bradykinin type 2 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Clin Invest (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1172/JCI14211"}], "href": "https://doi.org/10.1172/JCI14211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11956243"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11956243"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Irene D Bezemer, Lance A Bare, Carine J M Doggen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Gene variants associated with deep vein thrombosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "JAMA (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1001/jama.299.11.1306"}], "href": "https://doi.org/10.1001/jama.299.11.1306"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18349091"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18349091"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Alexey S Revenko, Dacao Gao, Jeff R Crosby, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selective depletion of plasma prekallikrein or coagulation factor XII inhibits thrombosis in mice without increased risk of bleeding."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2011-05-355248"}], "href": "https://doi.org/10.1182/blood-2011-05-355248"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21821705"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21821705"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Leif R Lund, Kirsty A Green, Allart A Stoop, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasminogen activation independent of uPA and tPA maintains wound healing in gene-deficient mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EMBO J (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.emboj.7601173"}], "href": "https://doi.org/10.1038/sj.emboj.7601173"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16763560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16763560"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zia Shariat-Madar, Fakhri Mahdi, Alvin H Schmaier "}, {"type": "b", "children": [{"type": "t", "text": "Recombinant prolylcarboxypeptidase activates plasma prekallikrein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-07-2510"}], "href": "https://doi.org/10.1182/blood-2003-07-2510"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14996700"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14996700"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Allen P Kaplan, Kusumam Joseph "}, {"type": "b", "children": [{"type": "t", "text": "Pathogenic mechanisms of bradykinin mediated diseases: dysregulation of an innate inflammatory pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Adv Immunol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/B978-0-12-800100-4.00002-7"}], "href": "https://doi.org/10.1016/B978-0-12-800100-4.00002-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24388213"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24388213"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "József Dobó, Balázs Major, Katalin A Kékesi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cleavage of kininogen and subsequent bradykinin release by the complement component: mannose-binding lectin-associated serine protease (MASP)-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0020036"}], "href": "https://doi.org/10.1371/journal.pone.0020036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21625439"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21625439"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Y Li, I D Bezemer, C M Rowland, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variants associated with deep vein thrombosis: the F11 locus."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2009.03544.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2009.03544.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19583818"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19583818"}]}]}]}
Synonyms	KLK3, PKKD
Proteins	KLKB1_HUMAN
NCBI Gene ID	3818
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

KLKB1 has 5,563 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 123 datasets.

Click the + buttons to view associations for KLKB1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

KLKB1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KLKB1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of KLKB1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of KLKB1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of KLKB1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of KLKB1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of KLKB1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving KLKB1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of KLKB1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of KLKB1 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 KLKB1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of KLKB1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of KLKB1 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 KLKB1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with KLKB1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of KLKB1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of KLKB1 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 KLKB1 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 KLKB1 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with KLKB1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of KLKB1 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of KLKB1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing KLKB1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing KLKB1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with KLKB1 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 KLKB1 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 KLKB1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with KLKB1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with KLKB1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with KLKB1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with KLKB1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by KLKB1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for KLKB1 protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with KLKB1 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 KLKB1 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 KLKB1 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 KLKB1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with KLKB1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for KLKB1 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at KLKB1 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 KLKB1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.