HABP2 Gene

Name	hyaluronan binding protein 2
Description	This gene encodes a member of the peptidase S1 family of serine proteases. The encoded preproprotein is secreted by hepatocytes and proteolytically processed to generate heavy and light chains that form the mature heterodimer. Further autoproteolysis leads to smaller, inactive peptides. This extracellular protease binds hyaluronic acid and may play a role in the coagulation and fibrinolysis systems. Mutations in this gene are associated with nonmedullary thyroid cancer and susceptibility to venous thromboembolism. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed. [provided by RefSeq, Jan 2016]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hyaluronan‐binding protein 2 (HABP2), also known as factor VII–activating protease (FSAP), is a multifunctional extracellular serine protease that plays diverse roles in vascular homeostasis, hemostasis, and tumor suppression. In the pulmonary endothelium, HABP2 expression is induced by inflammatory challenges such as lipopolysaccharide, and its enzymatic activity is regulated by hyaluronan fragments. Low–molecular‐weight hyaluronan enhances its activity, which in turn promotes protease‐activated receptor signaling and activates RhoA/Rho kinase pathways; these events contribute to disruption of endothelial barrier integrity and increased vascular permeability in acute lung injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of oncology, HABP2 exerts a tumor‐suppressive function in thyroid tissue. A germline variant, G534E, has been shown to abrogate its functional capacity, and this loss‐of‐function mutation is associated with familial nonmedullary thyroid cancer."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these roles, HABP2/FSAP is a key modulator of fibrinolysis and coagulation. It activates prourokinase and coagulation factor VII, thereby influencing vascular remodeling and controlling neointima formation. Genetic variants such as the Marburg I polymorphism and others that diminish HABP2’s proteolytic activity have been linked to increased risks of carotid stenosis, coronary heart disease, and ischemic stroke."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Recent work has also uncovered that extracellular nucleic acids serve as novel cofactors for HABP2 autoactivation. Both RNA and histones can bind to HABP2, enhancing its conversion to an active two‐chain enzyme and thereby linking tissue injury and inflammation to the modulation of proteolytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Moreover, HABP2 contributes to the regulation of the coagulation cascade by proteolytically degrading tissue factor pathway inhibitor, which further impacts vascular hemostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies illustrate that HABP2 functions as a critical regulator of both vascular integrity and fibrinolysis while also providing tumor‐suppressive signals. Disruption or genetic alteration of HABP2 impairs these essential processes and predisposes individuals to vascular diseases and certain cancers.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nurbek Mambetsariev, Tamara Mirzapoiazova, Bolot Mambetsariev, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hyaluronic Acid binding protein 2 is a novel regulator of vascular integrity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arterioscler Thromb Vasc Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/ATVBAHA.109.200451"}], "href": "https://doi.org/10.1161/ATVBAHA.109.200451"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20042707"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20042707"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sudheer Kumar Gara, Li Jia, Maria J Merino, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Germline HABP2 Mutation Causing Familial Nonmedullary Thyroid Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa1502449"}], "href": "https://doi.org/10.1056/NEJMoa1502449"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26222560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26222560"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Johann Willeit, Stefan Kiechl, Thomas Weimer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Marburg I polymorphism of factor VII--activating protease: a prominent risk predictor of carotid stenosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/01.cir.0000055189.18831.b1"}], "href": "https://doi.org/10.1161/01.cir.0000055189.18831.b1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12578864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12578864"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Daniel Sedding, Jan-Marcus Daniel, Lars Muhl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The G534E polymorphism of the gene encoding the factor VII-activating protease is associated with cardiovascular risk due to increased neointima formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20052546"}], "href": "https://doi.org/10.1084/jem.20052546"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17145954"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17145954"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Helen Ireland, George J Miller, Karen E Webb, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The factor VII activating protease G511E (Marburg) variant and cardiovascular risk."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH04-05-0275"}], "href": "https://doi.org/10.1160/TH04-05-0275"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15543324"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15543324"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Mariana S Parahuleva, Sandip M Kanse, Behnoush Parviz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Factor Seven Activating Protease (FSAP) expression in human monocytes and accumulation in unstable coronary atherosclerotic plaques."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Atherosclerosis (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.atherosclerosis.2007.03.042"}], "href": "https://doi.org/10.1016/j.atherosclerosis.2007.03.042"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17482622"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17482622"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Yu-Ching Cheng, Tara M Stanne, Anne-Katrin Giese, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-Wide Association Analysis of Young-Onset Stroke Identifies a Locus on Chromosome 10q25 Near HABP2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Stroke (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/STROKEAHA.115.011328"}], "href": "https://doi.org/10.1161/STROKEAHA.115.011328"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26732560"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26732560"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Matthew Traylor, Rainer Malik, Mike A Nalls, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variation at 16q24.2 is associated with small vessel stroke."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Ann Neurol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ana.24840"}], "href": "https://doi.org/10.1002/ana.24840"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27997041"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27997041"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Fumie Nakazawa, Christian Kannemeier, Aya Shibamiya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular RNA is a natural cofactor for the (auto-)activation of Factor VII-activating protease (FSAP)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BJ20041021"}], "href": "https://doi.org/10.1042/BJ20041021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15654766"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15654766"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Shingo Yamamichi, Yukari Fujiwara, Tadashi Kikuchi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Extracellular histone induces plasma hyaluronan-binding protein (factor VII activating protease) activation in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2011.05.030"}], "href": "https://doi.org/10.1016/j.bbrc.2011.05.030"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21600885"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21600885"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Malgorzata Wygrecka, Rory E Morty, Philipp Markart, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Plasminogen activator inhibitor-1 is an inhibitor of factor VII-activating protease in patients with acute respiratory distress syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M610748200"}], "href": "https://doi.org/10.1074/jbc.M610748200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17540775"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17540775"}]}]}]}
Synonyms	FSAP, HGFAL, NMTC5, HABP, PHBP
Proteins	HABP2_HUMAN
NCBI Gene ID	3026
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HABP2 has 4,273 functional associations with biological entities spanning 8 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 107 datasets.

Click the + buttons to view associations for HABP2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HABP2 Gene

Functional Associations

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

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by HABP2 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 HABP2 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 HABP2 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 HABP2 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 HABP2 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 HABP2 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HABP2 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 HABP2 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 HABP2 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 HABP2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HABP2 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 HABP2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HABP2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HABP2 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 HABP2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HABP2 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 HABP2 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HABP2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of HABP2 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 HABP2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HABP2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HABP2 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 HABP2 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HABP2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HABP2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HABP2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HABP2 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 HABP2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HABP2 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with HABP2 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 HABP2 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 HABP2 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 HABP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HABP2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for HABP2 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HABP2 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 HABP2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HABP2 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 HABP2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HABP2 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.