Coagulation Factor VIII (F8)

FVIII; AHF; HEMA; F8B; F8C; Antihemophilic Globulin; Hemophilia A; Anti-Hemophilic Factor A; FVIII Procoagulant Component; F8 Protein

SPN	U963
HGNC	3546
MGI	88383
PubMed	14660878
RGD	727845
UniProt	P00451
Wiki	Factor_VIII

Factor VIII (FVIII) is an essential blood clotting factor also known as anti-hemophilic factor (AHF). In humans, Factor VIII is encoded by the F8 gene. Defects in this gene results in hemophilia A, a well known recessive X-linked coagulation disorder.

Factor VIII participates in blood coagulation; it is a cofactor for factor IXa which, in the presence of Ca⁺² and phospholipids forms a complex that converts factor X to the activated form Xa. The Factor VIII 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.

Reference

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Nature 312:330-337(1984) [PubMed] [Europe PMC] [Abstract]

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Genomics 14:585-589(1992) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning of a cDNA encoding human antihaemophilic factor."
Nature 312:342-347(1984) [PubMed] [Europe PMC] [Abstract]

"Sequence of the exon-containing regions of the human factor VIII gene."
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Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]

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Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

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"Identification and functional importance of tyrosine sulfate residues within recombinant factor VIII."
Biochemistry 31:3315-3325(1992) [PubMed] [Europe PMC] [Abstract]

"The acidic region of the factor VIII light chain and the C2 domain together form the high affinity binding site for von Willebrand factor."
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Protein Sci. 4:740-746(1995) [PubMed] [Europe PMC] [Abstract]

"Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry."
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Biochemistry 34:3022-3031(1995) [PubMed] [Europe PMC] [Abstract]

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Blood 73:1-12(1989) [PubMed] [Europe PMC] [Abstract]

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Hum. Mutat. 5:1-22(1995) [PubMed] [Europe PMC] [Abstract]

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Science 232:1415-1416(1986) [PubMed] [Europe PMC] [Abstract]

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Nucleic Acids Res. 15:9797-9805(1987) [PubMed] [Europe PMC] [Abstract]

"Nonsense and missense mutations in hemophilia A: estimate of the relative mutation rate at CG dinucleotides."
Am. J. Hum. Genet. 42:718-725(1988) [PubMed] [Europe PMC] [Abstract]

"Moderately severe hemophilia A resulting from Glu-->Gly substitution in exon 7 of the factor VIII gene."
Am. J. Hum. Genet. 42:867-871(1988) [PubMed] [Europe PMC] [Abstract]

"Purification and characterization of factor VIII 1,689-Cys: a nonfunctional cofactor occurring in a patient with severe hemophilia A."
Blood 73:2117-2122(1989) [PubMed] [Europe PMC] [Abstract]

"An arginine to cysteine amino acid substitution at a critical thrombin cleavage site in a dysfunctional factor VIII molecule."
Blood 74:1612-1617(1989) [PubMed] [Europe PMC] [Abstract]

"A novel missense mutation in exon 4 of the factor VIII:C gene resulting in moderately severe hemophilia A."
Blood 74:2688-2691(1989) [PubMed] [Europe PMC] [Abstract]

"Mild hemophilia A resulting from Arg-to-Leu substitution in exon 26 of the factor VIII gene."
Hum. Genet. 81:335-338(1989) [PubMed] [Europe PMC] [Abstract]

"Direct characterization of factor VIII in plasma: detection of a mutation altering a thrombin cleavage site (arginine-372-->histidine)."
Proc. Natl. Acad. Sci. U.S.A. 86:4277-4281(1989) [PubMed] [Europe PMC] [Abstract]

"Characterization of a thrombin cleavage site mutation (Arg 1689 to Cys) in the factor VIII gene of two unrelated patients with cross-reacting material-positive hemophilia A."
Blood 75:384-389(1990) [PubMed] [Europe PMC] [Abstract]

"Recurrent mutations and three novel rearrangements in the factor VIII gene of hemophilia A patients of Italian descent."
Blood 75:662-670(1990) [PubMed] [Europe PMC] [Abstract]

"CRM+ haemophilia A due to a missense mutation (372-->Cys) at the internal heavy chain thrombin cleavage site."
Br. J. Haematol. 75:73-77(1990) [PubMed] [Europe PMC] [Abstract]

"Characterization of mutations in the factor VIII gene by direct sequencing of amplified genomic DNA."
Genomics 6:65-71(1990) [PubMed] [Europe PMC] [Abstract]

"Use of denaturing gradient gel electrophoresis to detect point mutations in the factor VIII gene."
Genomics 6:293-301(1990) [PubMed] [Europe PMC] [Abstract]

"Mutations and a polymorphism in the factor VIII gene discovered by denaturing gradient gel electrophoresis."
Proc. Natl. Acad. Sci. U.S.A. 87:2092-2096(1990) [PubMed] [Europe PMC] [Abstract]

"Identification of mutations in two families with sporadic hemophilia A."
Hum. Genet. 87:397-400(1991) [PubMed] [Europe PMC] [Abstract]

"Molecular characterization of severe hemophilia A suggests that about half the mutations are not within the coding regions and splice junctions of the factor VIII gene."
Proc. Natl. Acad. Sci. U.S.A. 88:7405-7409(1991) [PubMed] [Europe PMC] [Abstract]

"Molecular characterization of mild-to-moderate hemophilia A: detection of the mutation in 25 of 29 patients by denaturing gradient gel electrophoresis."
Proc. Natl. Acad. Sci. U.S.A. 88:8307-8311(1991) [PubMed] [Europe PMC] [Abstract]

"Detection and characterisation of two missense mutations at a cleavage site in the factor VIII light chain."
Thromb. Res. 61:225-234(1991) [PubMed] [Europe PMC] [Abstract]

"GAA(Glu)272->AAA(Lys) and CGA(Arg)1941->CAA(Gln) in the factor VIII gene in two haemophilia A patients of Czech origin."
Br. J. Haematol. 81:458-458(1992) [PubMed] [Europe PMC] [Abstract]

"Detection of mutations in the factor VIII gene using single-stranded conformational polymorphism (SSCP)."
Genomics 13:909-911(1992) [PubMed] [Europe PMC] [Abstract]

"Screening for nonsense mutations in patients with severe hemophilia A can provide rapid, direct carrier detection."
Hum. Genet. 89:88-94(1992) [PubMed] [Europe PMC] [Abstract]

"A novel mutation (Arg-->Leu in exon 18) in factor VIII gene responsible for moderate hemophilia A."
Hum. Mutat. 1:77-78(1992) [PubMed] [Europe PMC] [Abstract]

"Amino acid substitutions in conserved domains of factor VIII and related proteins: study of patients with mild and moderately severe hemophilia A."
Hum. Mutat. 1:248-257(1992) [PubMed] [Europe PMC] [Abstract]

"Missense mutations causing mild hemophilia A in Iceland detected by denaturing gradient gel electrophoresis."
Hum. Mutat. 1:506-508(1992) [PubMed] [Europe PMC] [Abstract]

"Spectrum of mutations in CRM-positive and CRM-reduced hemophilia A."
Genomics 15:392-398(1993) [PubMed] [Europe PMC] [Abstract]

"Double strand conformation polymorphism (DSCP) detects two point mutations at codon 280 (AAC-->ATC) and at codon 431 (TAC-->AAC) of the blood coagulation factor VIII gene."
Thromb. Haemost. 69:473-475(1993) [PubMed] [Europe PMC] [Abstract]

"Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients."
Blood 86:3015-3020(1995) [PubMed] [Europe PMC] [Abstract]

"Screening for mutations in haemophilia A patients by multiplex PCR-SSCP, Southern blotting and RNA analysis: the detection of a genetic abnormality in the factor VIII gene in 30 out of 35 patients."
Br. J. Haematol. 90:442-449(1995) [PubMed] [Europe PMC] [Abstract]

"Detection of mutations in ectopic factor VIII transcripts from nine haemophilia A patients and the correlation with phenotype."
Hum. Genet. 95:531-538(1995) [PubMed] [Europe PMC] [Abstract]

"Characterization of the factor VIII defect in 147 patients with sporadic hemophilia A: family studies indicate a mutation type-dependent sex ratio of mutation frequencies."
Am. J. Hum. Genet. 58:657-670(1996) [PubMed] [Europe PMC] [Abstract]

"Molecular characterization of haemophilia A in southern Chinese."
Br. J. Haematol. 93:451-456(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations in a subgroup of patients with mild haemophilia A and a familial discrepancy between the one-stage and two-stage factor VIII:C methods."
Br. J. Haematol. 94:400-406(1996) [PubMed] [Europe PMC] [Abstract]

"Mutations in the FVIII gene in seven families with mild haemophilia A."
Br. J. Haematol. 96:426-427(1997) [PubMed] [Europe PMC] [Abstract]

"Factor VIII gene analysis in Japanese CRM-positive and CRM-reduced haemophilia A patients by single-strand conformation polymorphism."
Br. J. Haematol. 98:901-906(1997) [PubMed] [Europe PMC] [Abstract]

"Mutational analysis of ectopic factor VIII transcripts from hemophilia A patients: identification of cryptic splice site, exon skipping and novel point mutations."
Hum. Genet. 100:508-511(1997) [PubMed] [Europe PMC] [Abstract]

"A domain mutations in 65 haemophilia A families and molecular modelling of dysfunctional factor VIII proteins."
Br. J. Haematol. 103:1051-1060(1998) [PubMed] [Europe PMC] [Abstract]

"Protein truncation test: detection of severe haemophilia a mutation and analysis of factor VIII transcripts."
Hum. Mutat. 11:18-22(1998) [PubMed] [Europe PMC] [Abstract]

"Independent occurrence of the novel Arg2163 to His mutation in the factor VIII gene in three unrelated families with haemophilia A with different phenotypes."
Hum. Mutat. 11:334-334(1998) [PubMed] [Europe PMC] [Abstract]

"Fluorescent chemical cleavage of mismatches for efficient screening of the factor VIII gene."
Hum. Mutat. 11:470-479(1998) [PubMed] [Europe PMC] [Abstract]

"Identification of four novel mutations in the factor VIII gene: three missense mutations (E1875G, G2088S, I2185T) and a 2-bp deletion (1780delTC)."
Hum. Mutat. Suppl. 1:S260-S262(1998) [PubMed] [Europe PMC] [Abstract]

"Molecular diagnostics of 15 hemophilia A patients: characterization of eight novel mutations in the factor VIII gene, two of which result in exon skipping."
Hum. Mutat. 12:301-303(1998) [PubMed] [Europe PMC] [Abstract]

"Use of denaturing gradient gel blots to screen for point mutations in the factor VIII gene."
Hum. Mutat. 12:393-402(1998) [PubMed] [Europe PMC] [Abstract]

"Precise carrier diagnosis in families with haemophilia A: use of conformation sensitive gel electrophoresis for mutation screening and polymorphism analysis."
Thromb. Haemost. 79:723-726(1998) [PubMed] [Europe PMC] [Abstract]

"Factor VIII inhibitors in mild and moderate-severity haemophilia A."
Thromb. Haemost. 79:762-766(1998) [PubMed] [Europe PMC] [Abstract]

"Diagnostic importance of the two-stage factor VIII:C assay demonstrated by a case of mild haemophilia associated with His1954-->Leu substitution in the factor VIII A3 domain."
Br. J. Haematol. 105:1123-1126(1999) [PubMed] [Europe PMC] [Abstract]

"Screen of 55 Slovenian haemophilia A patients: identification of 2 novel mutations (S-1R and IVS23+1G-->A) and discussion of mutation spectrum."
Hum. Mutat. 13:413-413(1999) [PubMed] [Europe PMC] [Abstract]

"Mutational-screening in the factor VIII gene resulting in the identification of three novel mutations, one of which is a donor splice mutation."
Hum. Mutat. 13:504-504(1999) [PubMed] [Europe PMC] [Abstract]

"Start of UK confidential haemophilia A database: analysis of 142 patients by solid phase fluorescent chemical cleavage of mismatch."
Thromb. Haemost. 81:900-905(1999) [PubMed] [Europe PMC] [Abstract]

"A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor."
Blood 96:958-965(2000) [PubMed] [Europe PMC] [Abstract]

"Hemophilic factor VIII C1- and C2-domain missense mutations and their modeling to the 1.5-angstrom human C2-domain crystal structure."
Blood 96:979-987(2000) [PubMed] [Europe PMC] [Abstract]

"Intracellular accumulation of factor VIII induced by missense mutations Arg593-->Cys and Asn618-->Ser explains cross-reacting material-reduced haemophilia A."
Br. J. Haematol. 108:241-246(2000) [PubMed] [Europe PMC] [Abstract]

"Assay discrepancy in mild haemophilia A due to a factor VIII missense mutation (Asn694Ile) in a large Danish family."
Br. J. Haematol. 109:523-528(2000) [PubMed] [Europe PMC] [Abstract]

"Experience of a single Italian center in genetic counseling for hemophilia: from linkage analysis to molecular diagnosis."
Haematologica 85:525-529(2000) [PubMed] [Europe PMC] [Abstract]

"Relationship between factor VIII mutation type and inhibitor development in a cohort of previously untreated patients treated with recombinant factor VIII (Recombinate)."
Thromb. Haemost. 83:844-848(2000) [PubMed] [Europe PMC] [Abstract]

"Mutations of the factor VIII gene in Thai hemophilia A patients."
Hum. Mutat. 15:117-118(2000) [PubMed] [Europe PMC] [Abstract]

"Somatic mosaicism in hemophilia A: a fairly common event."
Am. J. Hum. Genet. 69:75-87(2001) [PubMed] [Europe PMC] [Abstract]

"Lithuanian haemophilia A and B registry comprising phenotypic and genotypic data."
Br. J. Haematol. 112:1062-1070(2001) [PubMed] [Europe PMC] [Abstract]

"Site and type of mutations in the factor VIII gene in patients and carriers of haemophilia A."
Haemophilia 7:381-391(2001) [PubMed] [Europe PMC] [Abstract]

"Mild haemophilia A discovered in a previously multi-operated 73-year-old man: characterization of a new mutation."
Haemophilia 7:419-421(2001) [PubMed] [Europe PMC] [Abstract]

"Molecular pathology of haemophilia A in Turkish patients: identification of 36 independent mutations."
Haemophilia 7:475-481(2001) [PubMed] [Europe PMC] [Abstract]

"Seven novel and four recurrent point mutations in the factor VIII (F8C) gene."
Hum. Mutat. 18:546-546(2001) [PubMed] [Europe PMC] [Abstract]

"Rapid hemophilia A molecular diagnosis by a simple DNA sequencing procedure: identification of 14 novel mutations."
Thromb. Haemost. 85:580-583(2001) [PubMed] [Europe PMC] [Abstract]

Erratum
Thromb. Haemost. 86:727-727(2001)

"Skewed X-chromosome inactivation in monochorionic diamniotic twin sisters results in severe and mild hemophilia A."
Blood 100:3034-3036(2002) [PubMed] [Europe PMC] [Abstract]

"Factor VIII deficiency not induced by FVIII gene mutation in a female first cousin of two brothers with haemophilia A."
Br. J. Haematol. 119:390-392(2002) [PubMed] [Europe PMC] [Abstract]

"Three novel point mutations causing haemophilia A."
Haemophilia 8:715-718(2002) [PubMed] [Europe PMC] [Abstract]

"The identification and classification of 41 novel mutations in the factor VIII gene (F8C)."
Hum. Mutat. 19:274-278(2002) [PubMed] [Europe PMC] [Abstract]

"Identification of seven novel mutations of F8C by DHPLC."
Hum. Mutat. 20:231-232(2002) [PubMed] [Europe PMC] [Abstract]

"High throughput mutation screening of the factor VIII gene (F8C) in hemophilia A: 37 novel mutations and genotype-phenotype correlation."
Hum. Mutat. 20:267-274(2002) [PubMed] [Europe PMC] [Abstract]

"Non-inversion factor VIII mutations in 80 hemophilia A families including 24 with alloimmune responses."
Thromb. Haemost. 87:273-276(2002) [PubMed] [Europe PMC] [Abstract]

"11 hemophilia A patients without mutations in the factor VIII encoding gene."
Thromb. Haemost. 88:357-360(2002) [PubMed] [Europe PMC] [Abstract]

"Analysis of 18 novel mutations in the factor VIII gene."
Br. J. Haematol. 122:810-817(2003) [PubMed] [Europe PMC] [Abstract]

"Thirty-four novel mutations detected in factor VIII gene by multiplex CSGE: modeling of 13 novel amino acid substitutions."
J. Thromb. Haemost. 1:773-781(2003) [PubMed] [Europe PMC] [Abstract]

"Genotype and phenotype of haemophilia A in Thai patients."
Haemophilia 9:179-186(2003) [PubMed] [Europe PMC] [Abstract]

"Small FVIII gene rearrangements in 18 hemophilia A patients: five novel mutations."
Am. J. Hematol. 78:117-122(2005) [PubMed] [Europe PMC] [Abstract]

"Mutation analysis in 51 patients with haemophilia A: report of 10 novel mutations and correlations between genotype and clinical phenotype."
Haemophilia 11:133-141(2005) [PubMed] [Europe PMC] [Abstract]

"Female haemophilia A heterozygous for a de novo frameshift and a novel missense mutation of factor VIII."
J. Thromb. Haemost. 4:1969-1974(2006) [PubMed] [Europe PMC] [Abstract]

"Identification of 31 novel mutations in the F8 gene in Spanish hemophilia A patients: structural analysis of 20 missense mutations suggests new intermolecular binding sites."
Blood 111:3468-3478(2008) [PubMed] [Europe PMC] [Abstract]

"Identification of factor VIII gene mutations in patients with severe haemophilia A in Venezuela: identification of seven novel mutations."
Haemophilia 17:913-918(2011) [PubMed] [Europe PMC] [Abstract]

"Factor VIII Antigen, Activity, and Mutations in Hemophilia A."
Clin. Appl. Thromb. Hemost. 0:0-0(2014) [PubMed] [Europe PMC] [Abstract]