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    F8 coagulation factor VIII [ Homo sapiens (human) ]

    Gene ID: 2157, updated on 27-Nov-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
    mouse all
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    Genomic context

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    Location:
    Xq28
    Exon count:
    27
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (154835792..155022723, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (153072193..153259125, complement)
    RS_2024_09 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. [Glycosylation modifications improve secretion and activity of intein spliced coagulation factor VIII]. ZHU FX, et al. Zhonghua Yi Xue Za Zhi, 2010 Sep 28. PMID 21092465
    2. Clinical and genetic findings in five female patients with haemophilia A: Identification of a novel missense mutation, p.Phe2127Ser. MartĂ­n-Salces M, et al. Thromb Haemost, 2010 Oct. PMID 20664893
    3. Genotype and phenotype of haemophilia A in Thai patients. Yenchitsomanus P, et al. Haemophilia, 2003 Mar. PMID 12614369
    4. [Study on the Polymorphism of Intron 22 (CA)n Repeat within FVIII Gene in Dai, Yi and Han Populations of Yunnan Province]. Tai H, et al. Zhongguo Shi Yan Xue Ye Xue Za Zhi, 2000 Jun. PMID 12578706
    5. Effect of factor VIII on tissue factor-initiated spatial clot growth. Ovanesov MV, et al. Thromb Haemost, 2003 Feb. PMID 12574801

    See all (674) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.
      Title: A genetic association study of circulating coagulation factor VIII and von Willebrand factor levels.
    2. In-depth structure-function profiling of the complex formation between clotting factor VIII and heme.
      Title: In-depth structure-function profiling of the complex formation between clotting factor VIII and heme.
    3. 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.
    4. An intronic RNA element modulates Factor VIII exon-16 splicing.
      Title: An intronic RNA element modulates Factor VIII exon-16 splicing.
    5. 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.
    6. Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.
      Title: Coagulation factor VIII regulates von Willebrand factor homeostasis invivo.
    7. 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.
    8. Mechano-covalent protection of coagulation factor VIII by von Willebrand factor.
      Title: Mechano-covalent protection of coagulation factor VIII by von Willebrand factor.
    9. 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.
    10. 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.
    Submit: New GeneRIF Correction See all GeneRIFs (502)

    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)

    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_2024_08

    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

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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