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F8 coagulation factor VIII [ Homo sapiens (human) ]

Gene ID: 2157, updated on 31-Mar-2024

Summary

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Official Symbol
F8provided by HGNC
Official Full Name
coagulation factor VIIIprovided by HGNC
Primary source
HGNC:HGNC:3546
See related
Ensembl:ENSG00000185010 MIM:300841; AllianceGenome:HGNC:3546
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AHF; F8B; F8C; HEMA; FVIII; THPH13; DXS1253E
Summary
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]
Expression
Broad expression in fat (RPKM 7.9), lung (RPKM 6.4) and 23 other tissues See more
Orthologs
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Genomic context

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Location:
Xq28
Exon count:
27
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (154835792..155022723, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (153072193..153259125, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (154064067..154250998, complement)

Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30070 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30071 Neighboring gene high mobility group nucleosome binding domain 1 pseudogene 37 Neighboring gene small integral membrane protein 9 Neighboring gene int22h-1 recombination region Neighboring gene microRNA 1184-1 Neighboring gene H2A.B variant histone 1 Neighboring gene coagulation factor VIII associated 1 Neighboring gene eukaryotic translation elongation factor 1 alpha 1 pseudogene 31 Neighboring gene ZNF622 pseudogene 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chrX:154195537-154196736 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30072 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30073 Neighboring gene int1h-1 recombination region Neighboring gene Sharpr-MPRA regulatory region 4209 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21120 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 21121 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:154255797-154256700 Neighboring gene FUN14 domain containing 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:154285543-154286044 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 30074 Neighboring gene H3K27ac hESC enhancer GRCh37_chrX:154299323-154300044 Neighboring gene mature T cell proliferation 1 Neighboring gene C-X9-C motif containing 4

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. [Correlation Analysis of FⅧGene Mutation and the Production of FⅧ Inhibitor with Severe Hemophilia A Patients in a Single Medical Center]. Zhu LK, et al. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2022 Oct. PMID 36208262
  2. Translational readthrough at F8 nonsense variants in the factor VIII B domain contributes to residual expression and lowers inhibitor association. Testa MF, et al. Haematologica, 2023 Feb 1. PMID 35924581, Free PMC Article
  3. Factor XIII-A Val34Leu and Tyr204Phe variants influence clot kinetics in a cohort of South African type 2 diabetes mellitus patients. Phasha MN, et al. Gene, 2022 Aug 5. PMID 35671883
  4. Unveiling the influence of factor VIII physicochemical properties on hemophilia A phenotype through an in silico methodology. Meireles MR, et al. Comput Methods Programs Biomed, 2022 Jun. PMID 35367915
  5. Factor VIII as a potential player in cancer pathophysiology. Walker GE, et al. J Thromb Haemost, 2022 Mar. PMID 34847278, Free PMC Article

See all (662) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Long-term safety and efficacy outcomes of valoctocogene roxaparvovec gene transfer up to 6 years post-treatment.
    Title: Long-term safety and efficacy outcomes of valoctocogene roxaparvovec gene transfer up to 6 years post-treatment.
  2. An intronic RNA element modulates Factor VIII exon-16 splicing.
    Title: An intronic RNA element modulates Factor VIII exon-16 splicing.
  3. The role of proteolytic cleavage at Arg[336] and Arg[372] of the A1 domain in factor VIIa/tissue factor-catalyzed reactions of B domain-deleted factor VIII.
    Title: The role of proteolytic cleavage at Arg(336) and Arg(372) of the A1 domain in factor VIIa/tissue factor-catalyzed reactions of B domain-deleted factor VIII.
  4. Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.
    Title: Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.
  5. Factor VIII mutated with Lys1813Ala within the factor IXa-binding region enhances intrinsic coagulation potential.
    Title: Factor VIII mutated with Lys1813Ala within the factor IXa-binding region enhances intrinsic coagulation potential.
  6. Mechano-covalent protection of coagulation factor VIII by von Willebrand factor.
    Title: Mechano-covalent protection of coagulation factor VIII by von Willebrand factor.
  7. Translational readthrough at F8 nonsense variants in the factor VIII B domain contributes to residual expression and lowers inhibitor association.
    Title: Translational readthrough at F8 nonsense variants in the factor VIII B domain contributes to residual expression and lowers inhibitor association.
  8. Heterogeneity and reciprocity of FVIII and VWF expression, and the response to shear stress in cultured human endothelial cells.
    Title: Heterogeneity and reciprocity of FVIII and VWF expression, and the response to shear stress in cultured human endothelial cells.
  9. [Correlation Analysis of FGene Mutation and the Production of F Inhibitor with Severe Hemophilia A Patients in a Single Medical Center].
    Title: [Correlation Analysis of FⅧGene Mutation and the Production of FⅧ Inhibitor with Severe Hemophilia A Patients in a Single Medical Center].
  10. Factor XIII-A Val34Leu and Tyr204Phe variants influence clot kinetics in a cohort of South African type 2 diabetes mellitus patients.
    Title: Factor XIII-A Val34Leu and Tyr204Phe variants influence clot kinetics in a cohort of South African type 2 diabetes mellitus patients.
Submit: New GeneRIF Correction See all GeneRIFs (500)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Hereditary factor VIII deficiency disease
MedGen: C0019069 OMIM: 306700 GeneReviews: Hemophilia A
Compare labs
Thrombophilia, X-linked, due to factor 8 defect
MedGen: C5676879 OMIM: 301071 GeneReviews: Not available
Compare labs

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated 2020-10-13)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-10-13)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Genetically distinct subsets within ANCA-associated vasculitis.
EBI GWAS Catalog
Genome-wide association analysis of red blood cell traits in African Americans: the COGENT Network.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env HIV-1 gp120-treated vaginal epithelial cells show upregulation of coagulation factor VIII (F8) expression as compared to untreated control PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables copper ion binding IEA
Inferred from Electronic Annotation
more info
  
enables oxidoreductase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in acute-phase response IEA
Inferred from Electronic Annotation
more info
  
involved_in blood coagulation TAS
Traceable Author Statement
more info
 PubMed 
involved_in blood coagulation, intrinsic pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in COPII-coated ER to Golgi transport vesicle TAS
Traceable Author Statement
more info
  
located_in Golgi lumen TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum lumen TAS
Traceable Author Statement
more info
  
located_in endoplasmic reticulum-Golgi intermediate compartment membrane TAS
Traceable Author Statement
more info
  
located_in extracellular region NAS
Non-traceable Author Statement
more info
 PubMed 
located_in extracellular region TAS
Traceable Author Statement
more info
  
is_active_in extracellular space IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in plasma membrane TAS
Traceable Author Statement
more info
  
located_in platelet alpha granule lumen TAS
Traceable Author Statement
more info
  

General protein information

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Preferred Names
coagulation factor VIII
Names
antihemophilic factor
coagulation factor VIII A1 domain
coagulation factor VIII C2 domain
coagulation factor VIII, procoagulant component
coagulation factor VIIIc
factor VIII F8B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_011403.2 RefSeqGene

    Range
    5001..191932
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_555

mRNA and Protein(s)

  1. NM_000132.4 → NP_000123.1  coagulation factor VIII isoform a preproprotein

    See identical proteins and their annotated locations for NP_000123.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) consists of 26 exons and encodes the full-length isoform (a).
    Source sequence(s)
    AC109993, BC022513, M14113
    Consensus CDS
    CCDS35457.1
    UniProtKB/Swiss-Prot
    P00451, Q14286, Q5HY69
    Related
    ENSP00000353393.4, ENST00000360256.9
    Conserved Domains (8) summary
    smart00231
    Location:2039 → 2188
    FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain
    cd00057
    Location:2195 → 2344
    FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
    cd04227
    Location:399 → 575
    CuRO_3_FVIII_like; The third cupredoxin domain of coagulation factor VIII and similar proteins
    cd04228
    Location:1714 → 1880
    CuRO_5_FVIII_like; The fifth cupredoxin domain of coagulation factor VIII and similar proteins
    cd11015
    Location:211 → 345
    CuRO_2_FVIII_like; The second cupredoxin domain of coagulation factor VIII and similar proteins
    cd11016
    Location:588 → 730
    CuRO_4_FVIII_like; The fourth cupredoxin domain of coagulation factor VIII and similar proteins
    cd11018
    Location:1892 → 2035
    CuRO_6_FVIII_like; The sixth cupredoxin domain of coagulation factor VIII and similar proteins
    cd14452
    Location:22 → 201
    CuRO_1_FVIII_like; The first cupredoxin domain of coagulation factor VIII and similar proteins

  2. NM_019863.3 → NP_063916.1  coagulation factor VIII isoform b

    See identical proteins and their annotated locations for NP_063916.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) contains an unique 5' exon located within intron 22 of transcript variant 1. This exon codes for eight amino acids and is spliced to exons 23-26 maintaining the reading frame. The resulting isoform (b) is considerably shorter compared to isoform a, and includes the phospholipid binding domain.
    Source sequence(s)
    AC109993, BX842559
    Consensus CDS
    CCDS44026.1
    UniProtKB/Swiss-Prot
    P00451
    Related
    ENSP00000327895.6, ENST00000330287.10
    Conserved Domains (2) summary
    cd00057
    Location:60 → 209
    FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.
    cl25480
    Location:4 → 52
    FA58C; Coagulation factor 5/8 C-terminal domain, discoidin domain; Cell surface-attached carbohydrate-binding domain, present in eukaryotes and assumed to have horizontally transferred to eubacterial genomes.

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

    Range
    154835792..155022723 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060947.1 Alternate T2T-CHM13v2.0

    Range
    153072193..153259125 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P00451.1 GenPept UniProtKB/Swiss-Prot:P00451

Gene LinkOut

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