F8 Gene

Name	coagulation factor VIII, procoagulant component
Description	This gene encodes coagulation factor VIII, which participates in the intrinsic pathway of blood coagulation; factor VIII is a cofactor for factor IXa which, in the presence of Ca+2 and phospholipids, converts factor X to the activated form Xa. This gene produces two alternatively spliced transcripts. Transcript variant 1 encodes a large glycoprotein, isoform a, which circulates in plasma and associates with von Willebrand factor in a noncovalent complex. This protein undergoes multiple cleavage events. Transcript variant 2 encodes a putative small protein, isoform b, which consists primarily of the phospholipid binding domain of factor VIIIc. This binding domain is essential for coagulant activity. Defects in this gene results in hemophilia A, a common recessive X-linked coagulation disorder. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Coagulation factor VIII is an essential pro‐coagulant protein that plays a central role in the intrinsic pathway of blood coagulation. In circulation, it forms a tight noncovalent complex with von Willebrand factor (VWF), which not only protects it from premature clearance but also positions it to act as a cofactor for factor IXa in converting factor X to its active form – a key step in thrombin generation and subsequent fibrin clot formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Although present at relatively low concentrations compared with other coagulation proteins, factor VIII is synthesized by several cell types – with hepatic non‐parenchymal cells such as sinusoidal endothelial cells and Kupffer cells, along with renal and possibly lung endothelial cells, contributing to its production."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Its post‐translational modifications, including extensive glycosylation (notably within its B domain), are critical determinants of its intracellular trafficking and plasma clearance. Specific receptors – such as members of the LDL receptor family (including LRP1) and the asialoglycoprotein receptor (ASGPR) – mediate factor VIII clearance; these interactions are modulated by the presence of VWF, which functions as an effective chaperone."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic defects that diminish factor VIII expression or function result in hemophilia A, a bleeding diathesis characterized by inefficient clot formation due to impaired thrombin generation and dysregulated fibrinolysis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Moreover, mutations affecting intracellular transport proteins (for example, those in the LMAN1–MCFD2 complex) have highlighted the importance of proper trafficking for effective secretion of factor VIII."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " In patients with hemophilia A, immunogenicity toward factor VIII can lead to the development of inhibitory antibodies that compromise replacement therapy, a challenge that has spurred efforts to bioengineer recombinant variants such as Fc‐fusion proteins which extend the half‐life of factor VIII without disrupting its essential interactions with VWF."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Conversely, elevated plasma levels of factor VIII have been strongly associated with an increased risk of venous and arterial thrombotic events. Genetic polymorphisms that modulate the interactions of factor VIII with its clearance receptors can contribute to prothrombotic states, emphasizing the delicate balance between synthesis, activation, and removal that is critical for normal hemostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Nicholas L Smith, Ming-Huei Chen, Abbas Dehghan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel associations of multiple genetic loci with plasma levels of factor VII, factor VIII, and von Willebrand factor: The CHARGE (Cohorts for Heart and Aging Research in Genome Epidemiology) Consortium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Circulation (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1161/CIRCULATIONAHA.109.869156"}], "href": "https://doi.org/10.1161/CIRCULATIONAHA.109.869156"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20231535"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20231535"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Steven W Pipe, Robert R Montgomery, Kathleen P Pratt, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Life in the shadow of a dominant partner: the FVIII-VWF association and its clinical implications for hemophilia A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2016-04-713289"}], "href": "https://doi.org/10.1182/blood-2016-04-713289"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27587878"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27587878"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "M J Hollestelle, T Thinnes, K Crain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue distribution of factor VIII gene expression in vivo--a closer look."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2001)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11583319"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11583319"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Martine J Hollestelle, Hendrika G M Geertzen, Irene H Straatsburg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Factor VIII expression in liver disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1160/TH03-05-0310"}], "href": "https://doi.org/10.1160/TH03-05-0310"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14961153"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14961153"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "N Bovenschen, D C Rijken, L M Havekes, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The B domain of coagulation factor VIII interacts with the asialoglycoprotein receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1538-7836.2005.01389.x"}], "href": "https://doi.org/10.1111/j.1538-7836.2005.01389.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15946216"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15946216"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Nicola Martinelli, Domenico Girelli, Barbara Lunghi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Polymorphisms at LDLR locus may be associated with coronary artery disease through modulation of coagulation factor VIII activity and independently from lipid profile."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2010-03-277079"}], "href": "https://doi.org/10.1182/blood-2010-03-277079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20810930"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20810930"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "L O Mosnier, T Lisman, H M van den Berg, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The defective down regulation of fibrinolysis in haemophilia A can be restored by increasing the TAFI plasma concentration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Thromb Haemost (2001)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11686321"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11686321"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Bin Zhang, Randal J Kaufman, David Ginsburg "}, {"type": "b", "children": [{"type": "t", "text": "LMAN1 and MCFD2 form a cargo receptor complex and interact with coagulation factor VIII in the early secretory pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M502160200"}], "href": "https://doi.org/10.1074/jbc.M502160200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15886209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15886209"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Shawn F J Whelan, Christoph J Hofbauer, Frank M Horling, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct characteristics of antibody responses against factor VIII in healthy individuals and in different cohorts of hemophilia A patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2012-07-444877"}], "href": "https://doi.org/10.1182/blood-2012-07-444877"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23243272"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23243272"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "R T Peters, G Toby, Q Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Biochemical and functional characterization of a recombinant monomeric factor VIII-Fc fusion protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jth.12076"}], "href": "https://doi.org/10.1111/jth.12076"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23205847"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23205847"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "I M Rietveld, W M Lijfering, S le Cessie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High levels of coagulation factors and venous thrombosis risk: strongest association for factor VIII and von Willebrand factor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Thromb Haemost (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/jth.14343"}], "href": "https://doi.org/10.1111/jth.14343"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30471183"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30471183"}]}]}]}
Synonyms	FVIII, DXS1253E, HEMA, AHF, F8B, F8C
Proteins	FA8_HUMAN
NCBI Gene ID	2157
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

F8 has 8,688 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 122 datasets.

Click the + buttons to view associations for F8 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

F8 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 F8 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 F8 gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 F8 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 F8 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 F8 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving F8 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of F8 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 F8 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 F8 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 F8 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 F8 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with F8 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with F8 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with F8 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 F8 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of F8 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 F8 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 F8 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of F8 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing F8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing F8 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with F8 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 F8 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 F8 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with F8 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with F8 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with F8 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of F8 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by F8 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with F8 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 F8 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 F8 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 F8 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 F8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with F8 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for F8 protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at F8 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 F8 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of F8 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 F8 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.