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F8 Gene

protein-coding GIFtS: 66
GCID: GC0XM154064

Coagulation Factor VIII, Procoagulant Component

(Previous symbol: F8C)

See F8-related diseases
at

MalaCards

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Coagulation Factor VIII, Procoagulant Component¹ ²		DXS1253E²
F8C¹ ² ³ ⁵		F8B²
Antihemophilic Factor² ³		FVIII²
AHF² ³		Coagulation Factor VIII²
HEMA² ⁵		Coagulation Factor VIIIc²
Factor VIIIF8B¹		Factor VIII F8B²
Hemophilia A¹		Procoagulant Component³

External Ids:	HGNC: 3546¹	Entrez Gene: 2157²	Ensembl: ENSG00000185010⁷	OMIM: 300841⁵	UniProtKB: P00451³

Export aliases for F8 gene to outside databases

Previous GC identifers: GC0XM148127 GC0XM150444 GC0XM151651 GC0XM152532 GC0XM153627 GC0XM153717 GC0XM142607

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for F8 Gene:

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)

GeneCards Summary for F8 Gene:

F8 (coagulation factor VIII, procoagulant component) is a protein-coding gene. Diseases associated with F8 include moderately severe hemophilia a, and type 2n von willebrand disease. GO annotations related to this gene include oxidoreductase activity and copper ion binding. An important paralog of this gene is DCBLD1.

UniProtKB/Swiss-Prot: FA8_HUMAN, P00451

Function: Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts

factor X to the activated form, factor Xa

Gene Wiki entry for F8 (Factor VIII) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:

NC_000023.10 NC_018934.2 NT_011681.17

Regulatory elements:

Regulatory transcription factor binding sites in the F8 gene promoter:
GR GR-beta Nkx2-5 GR-alpha
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): F8 promoter sequence

Search Chromatin IP Primers for F8

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat F8

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: Xq28 Ensembl cytogenetic band: Xq28 HGNC cytogenetic band: Xq28

F8 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
F8 gene location

GeneLoc information about chromosome X GeneLoc Exon Structure

GeneLoc location for GC0XM154064: view genomic region (about GC identifiers)

Start:	154,064,063 bp from pter	End:	154,255,215 bp from pter
Size:	191,153 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: FA8_HUMAN, P00451 (See protein sequence)

Recommended Name: Coagulation factor VIII precursor

Size: 2351 amino acids; 267009 Da

Subunit: Interacts with vWF. vWF binding is essential for the stabilization of F8 in circulation

Mass spectrometry: Mass=1367.6; Method=Electrospray; Range=356-378; Note=Nonsulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=1407.4; Method=Electrospray; Range=356-378; Note=Sulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=2975.4; Method=Electrospray; Range=400-424; Note=Nonsulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=3024; Method=Electrospray; Range=727-752; Note=Nonsulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=3104; Method=Electrospray; Range=727-752; Note=Monosulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=3183.5; Method=Electrospray; Range=727-752; Note=Disulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=3262.5; Method=Electrospray; Range=727-752; Note=Trisulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=2460.9; Method=Electrospray; Range=1672-1692; Note=Nonsulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=2540.7; Method=Electrospray; Range=1672-1692; Note=Sulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=2000.7; Method=Electrospray; Range=1691-1708; Note=Nonsulfated; Source=PubMed:10368977;

Mass spectrometry: Mass=2080.7; Method=Electrospray; Range=1691-1708; Note=Sulfated; Source=PubMed:10368977;

Selected PDB 3D structures from and Proteopedia for F8 (see all 13):

1CFG (3D)

1D7P (3D)

1FAC (3D)

1IQD (3D)

2R7E (3D)

3CDZ (3D)

Secondary accessions: Q14286 Q5HY69

Alternative splicing: 2 isoforms: P00451-1 P00451-2

Explore the universe of human proteins at neXtProt for F8: NX_P00451

Explore proteomics data for F8 at MOPED

Post-translational modifications:

Sulfation on Tyr-1699 is essential for binding vWF¹

Glycosylation² at Asn60, Asn258, Asn601, Asn776, Asn803, Asn847, Asn919, Asn962, Asn982, Asn1020,
Asn1024, Asn1074, Asn1085, Asn1204, Asn1274, Asn1278, Asn1301, Asn1319, Asn1431, Asn1461 (see all 22)

Modification sites at PhosphoSitePlus

See F8 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins (2 alternative transcripts):

NP_000123.1 NP_063916.1

ENSEMBL proteins:

ENSP00000327895 ENSP00000353393 ENSP00000409446 ENSP00000389153

Reactome Protein details: P00451

F8 Human Recombinant Protein Products:

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	ProSpec Recombinant Protein for F8
	Cloud-Clone Corp. Proteins for F8
	Search eBioscience for Proteins for F8
	antibodies-online proteins for F8 (17 products)
	antibodies-online peptides for F8

F8 Antibody Products:

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	Abcam antibodies for F8
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	ThermoFisher Antibody for F8
	antibodies-online antibodies for F8 (56 products)

F8 Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	GenScript Custom Assay Services for F8
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for F8 Cloud-Clone Corp. CLIAs for F8
	Search eBioscience for ELISAs for F8
	antibodies-online kits for F8 (27 products)

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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Selected InterPro protein domains (see all 8):

IPR024715 Factor_5/8

IPR011707 Cu-oxidase_3

IPR008979 Galactose-bd-like

IPR011706 Cu-oxidase_2

IPR008972 Cupredoxin

Graphical View of Domain Structure for InterPro Entry P00451

ProtoNet protein and cluster: P00451

3 Blocks protein domains:

IPB000421 Coagulation factor 5/8 type C domain (FA58C)

IPB001117 Multicopper oxidase

IPB011706 Multicopper oxidase

UniProtKB/Swiss-Prot: FA8_HUMAN, P00451

Domain: Domain F5/8 type C 2 is responsible for phospholipid-binding and essential for factor VIII activity

Similarity: Belongs to the multicopper oxidase family

Similarity: Contains 3 F5/8 type A domains

Similarity: Contains 2 F5/8 type C domains

Similarity: Contains 6 plastocyanin-like domains

Find genes that share domains with F8 About GenesLikeMe

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: FA8_HUMAN, P00451

Function: Factor VIII, along with calcium and phospholipid, acts as a cofactor for factor IXa when it converts

factor X to the activated form, factor Xa

Gene Ontology (GO): 4 molecular function terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004252	serine-type endopeptidase activity	IEA	--
GO:0005507	copper ion binding	IEA	--
GO:0005515	protein binding	IPI	7756647
GO:0016491	oxidoreductase activity	IEA	--

Find genes that share ontologies with F8 About GenesLikeMe

Phenotypes:
1 GenomeRNAi human phenotype for F8:

Increased cell death HMECs cel

5 MGI mutant phenotypes (inferred from 2 alleles) (MGI details for F8):

hematopoietic system

homeostasis/metabolism

immune system

mortality/aging

reproductive system

Find genes that share phenotypes with F8 About GenesLikeMe

Animal Models:
MGI mouse knock-outs for F8: F8^tm1Kaz F8^tm2Kaz

genOway: Develop your customized and physiologically relevant rodent model for F8

miRNA Products:		Block miRNA regulation of human, mouse, rat F8 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate F8 (see all 11):
		hsa-miR-4291 hsa-miR-1290 hsa-miR-539 hsa-miR-548aa hsa-miR-214 hsa-miR-542-3p hsa-miR-3121-3p hsa-miR-297

		SwitchGear 3'UTR luciferase reporter plasmid: F8 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for F8
		Predesigned siRNA for gene silencing in human, mouse, rat F8

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for F8

Clone Products:		OriGene clones in human, mouse for F8 (see all 12) OriGene ORF clones in mouse, rat for F8 OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript Custom all cDNA clones Services for F8
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for F8
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat F8
		Addgene plasmids for F8

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for F8
		Browse ESI BIO Cell Lines and PureStem Progenitors for F8

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for F8

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

FA8_HUMAN, P00451: Secreted, extracellular space

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
extracellular	5
plasma membrane	4
cytoskeleton	3
endoplasmic reticulum	2
nucleus	2
endosome	1
golgi apparatus	1
lysosome	1
mitochondrion	1

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Gene Ontology (GO): 4 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005615	extracellular space	IEA	--
GO:0005886	plasma membrane	TAS	--
GO:0031093	platelet alpha granule lumen	TAS	--

Find genes that share ontologies with F8 About GenesLikeMe

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for F8 About

See pathways by source

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SuperPath

Contained pathways About

Formation of Fibrin Clot (Clotting Cascade)

	Formation of Fibrin Clot (Clotting Cascade)	0.51			Blood Clotting Cascade	0.42
	Blood Coagulation Signaling Pathways	0.51			Intrinsic Pathway	0.00

Complement and coagulation cascades

Complement and coagulation cascades

0.71

Complement and Coagulation Cascades

0.71

Response to elevated platelet cytosolic Ca2+

Response to elevated platelet cytosolic Ca2+

0.94

Platelet degranulation

0.94

Hemostasis

Platelet activation, signaling and aggregation

0.43

Hemostasis

0.43

Collagen biosynthesis and modifying enzymes

Intrinsic Prothrombin Activation Pathway

0.39

Blood Coagulation Cascade

0.38

Find genes that share SuperPaths with F8 About GenesLikeMe

Pathways by source See SuperPaths
Show all pathways

1 R&D Systems Pathway for F8

Blood Coagulation Signaling Pathways

2 Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for F8

	Blood Coagulation Cascade
	Intrinsic Prothrombin Activation Pathway

2 BioSystems Pathways for F8

	Blood Clotting Cascade
	Complement and Coagulation Cascades

2 Reactome Pathways for F8

	Platelet degranulation
	Intrinsic Pathway

1 Kegg Pathway (Kegg details for F8):

Complement and coagulation cascades

Pathway & Disease-focused RT² Profiler PCR Arrays including F8:

NFKB Signaling Targets in human mouse rat

Lymphoma in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

Interactions:

GeneGlobe Interaction Network for F8

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

Selected Interacting proteins for F8 (P00451^{2, 3} ENSP00000353393⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 62)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
LRP1	Q07954³, ENSP00000243077⁴	I2D: score=3 STRING: ENSP00000243077
VWF	P04275³, ENSP00000261405⁴	I2D: score=3 STRING: ENSP00000261405
CALR	P27797³, ENSP00000320866⁴	I2D: score=2 STRING: ENSP00000320866
HSPA5	P11021³, ENSP00000324173⁴	I2D: score=2 STRING: ENSP00000324173
F2	P00734³, ENSP00000308541⁴	I2D: score=1 STRING: ENSP00000308541

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Gene Ontology (GO): Selected biological process terms (see all 7): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0002576	platelet degranulation	TAS	--
GO:0006953	acute-phase response	IEA	--
GO:0007155	cell adhesion	IEA	--
GO:0007596	blood coagulation	TAS	--
GO:0007597	blood coagulation, intrinsic pathway	TAS	--

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(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for F8 (FA8)

UniProtKB/Swiss-Prot: FA8_HUMAN, P00451

Pharmaceutical: Available under the names Kogenate (Bayer) and Recombinate (Baxter and American Home Products).

Used to treat hemophilia A

1 HMDB Compound for F8 About this table

Compound	Synonyms	CAS #	PubMed Ids
Calcium	Ca (see all 2)	7440-70-2	--

2 DrugBank Compounds for F8 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Coagulation Factor IX	Christmas factor (see all 4)	9001-28-9	target	cofactor	11150722 659613 16476097 12719776 14598591 12826528
Drotrecogin alfa	Anticoagulant protein C (see all 4)	60202-16-6	target	multitarget	18954704 11752352 9184404

Selected Novoseek inferred chemical compound relationships for F8 gene (see all 95) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
rfviii	94.3	104	1899619 (4), 8756394 (3), 11187864 (3), 12216115 (3) (see all 42)
kogenate	90.7	30	10979218 (3), 16926139 (2), 11380627 (1), 18416588 (1) (see all 15)
ristocetin	89.7	113	17586991 (3), 10744159 (2), 7572006 (2), 1703813 (1) (see all 79)
refacto	87.1	42	15102018 (4), 19298379 (4), 17610548 (4), 17286764 (4) (see all 10)
desmopressin	86.1	218	10929043 (8), 8322282 (5), 7819109 (5), 8874865 (5) (see all 82)
recombinate	85.4	13	1448776 (1), 11442642 (1), 17456190 (1), 1457586 (1) (see all 10)
helixate	76.1	4	18416588 (1)
fibrinogen	73.2	184	1585439 (5), 16362590 (3), 18289163 (3), 10886222 (3) (see all 99)
tributylphosphate	57.2	8	16507321 (2), 16756602 (2), 1697997 (1)
rituximab	49.6	12	17212724 (3), 19320828 (2), 12384448 (1), 18414981 (1) (see all 9)

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(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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REFSEQ mRNAs for F8 gene (2 alternative transcripts):

NM_000132.3 NM_019863.2

Unigene Clusters for F8:

Coagulation factor VIII, procoagulant component

Hs.632836 [show with all ESTs], Hs.654450 [show with all ESTs]

Unigene Representative Sequences: BG105416, NM_000132

5 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000330287(uc004fms.3) ENST00000360256(uc010nvi.1 uc004fmt.3)

ENST00000483822 ENST00000423959(uc011mzx.1) ENST00000453950

miRNA Products:		Block miRNA regulation of human, mouse, rat F8 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate F8 (see all 11):
		hsa-miR-4291 hsa-miR-1290 hsa-miR-539 hsa-miR-548aa hsa-miR-214 hsa-miR-542-3p hsa-miR-3121-3p hsa-miR-297

		SwitchGear 3'UTR luciferase reporter plasmid: F8 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for F8
		Predesigned siRNA for gene silencing in human, mouse, rat F8

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		GenScript Custom all cDNA clones Services for F8
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for F8
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat F8
		Addgene plasmids for F8

Primer Products:		OriGene qPCR primer pairs and template standards for F8 OriGene qSTAR qPCR primer pairs in human, mouse for F8
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat F8
		QuantiTect SYBR Green Assays in human, mouse, rat F8
		QuantiFast Probe-based Assays in human, mouse, rat F8

Additional mRNA sequence:

AK289947.1 AK292902.1 AK295164.1 AK307726.1 AK313707.1 BC022513.1 BC064380.1 BC098389.1

BC111967.1 BC111969.1 BC150305.1 FN811132.1 K01740.1 M14113.1 M90707.1 X01179.1

13 DOTS entries:

DT.95361537 DT.442566 DT.415840 DT.95206260 DT.100779256 DT.91852393 DT.100742082 DT.100030151

DT.121312596 DT.95156169 DT.121291745 DT.454648 DT.91729072

Selected AceView cDNA sequences (see all 86):

CA389921 NM_000132 BX951926 F12385 NM_019863 BQ721191 BU855229 CD557999

BC022513 BQ880871 X01179 CB054305 CK826280 BQ548947 BX280670 D45586

BX489830 BC064380 BQ548655 M14113 M90707 BX501434 BM548207 CB994611

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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F8 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: AAGACGTACC

About this image

F8 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

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F8 Protein Expression

SOURCE GeneReport for Unigene clusters: Hs.632836 Hs.654450

Pathway & Disease-focused RT² Profiler PCR Arrays including F8:

NFKB Signaling Targets in human mouse rat

Lymphoma in human mouse rat

Inflammatory Response & Autoimmunity 384HT in human mouse rat

Primer Products:		OriGene qPCR primer pairs and template standards for F8 OriGene qSTAR qPCR primer pairs in human, mouse for F8
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat F8
		QuantiTect SYBR Green Assays in human, mouse, rat F8
		QuantiFast Probe-based Assays in human, mouse, rat F8

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for F8

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for F8 gene from Selected species (see all 11) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	F8^{1 , 5}	coagulation factor VIII^{1, 5}	82.16(n)¹ 74.22(a)¹		X (38.17 cM)⁵ 14069¹ NM_007977.2¹ NP_032003.2¹ 75172715⁵
chicken (Gallus gallus)	Aves	F8⁶	coagulation factor VIII, procoagulant component	46(a)	1 ↔ 1	4(2122995-2142344)
lizard (Anolis carolinensis)	Reptilia	F8⁶	coagulation factor VIII, procoagulant component	40(a)	1 ↔ 1	GL343528.1(343968-377523)
zebrafish (Danio rerio)	Actinopterygii	f8⁶	coagulation factor VIII, procoagulant component	31(a)	1 ↔ 1	14(1005561-1038983) ENSDARG00000015247

ENSEMBL Gene Tree for F8 (if available)
TreeFam Gene Tree for F8 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for F8 gene

DCBLD1² EDIL3² MFGE8² DCBLD2² NRP1² RS1² NRP2² F5²

11 SIMAP similar genes for F8 using alignment to 52 protein entries: FA8_HUMAN (see all proteins):

F8A1 F8C F8c SPAG10 MFGE8 F5

factor V RS1 CP HEPHL1 HEPH

Find genes that share paralogs with F8 About GenesLikeMe

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr X pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs28937294^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154132300(-)	`GATTCA/G/TATGGT`	6	Q R L	mis¹		0	--	--	--	--
rs28933682^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154132357(-)	`AATCAA/GTGGCT`	4	N S	mis¹ ese³		0	--	--	--	--
rs28933681^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154132676(-)	`TTGATA/GAGACC`	4	K E	mis¹ ese³		0	--	--	--	--
rs28933680^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154132768(-)	`TGGACC/GCCTTC`	4	P R	mis¹ ese³		0	--	--	--	--
rs28933679^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154132786(-)	`TGTGCA/GCTCAG`	4	H R	mis¹ ese³		0	--	--	--	--
rs28933677^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154133114(-)	`CAAAGC/TCTGGG`	4	A V	mis¹		0	--	--	--	--
rs28933676^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154133139(-)	`CACCCA/CCTAAA`	4	T P	mis¹ ese³		0	--	--	--	--
rs28933675^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154133142(-)	`TGGCAC/TCCACT`	4	P S	mis¹ ese³		0	--	--	--	--
rs28933674^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154133146(-)	`CATATA/GGCACC`	4	I M	mis¹ ese³		0	--	--	--	--
rs28935203^1,2,,4	C	Hemophilia A (HEMA)⁴ pathogenic¹	154156969(-)	`CATTTA/TTGATG`	4	Y F	mis¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for F8 (154064063 - 154255215 bp)

Structural Variations
Database of Genomic Variants (DGV) 2 variations for F8: About this table

Variant ID	Type	Subtype	PubMed ID
esv29972	CNV	Gain	17803354
esv33784	CNV	Gain+Loss	17666407

Human Gene Mutation Database (HGMD): F8
Locus Specific Mutation Databases (LSDB): F8

Site Specific Mutation Identification with PCR Assays

SeqTarget long-range PCR primers for resequencing F8

DNA2.0 Custom Variant and Variant Library Synthesis for F8

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 300841
OMIM disorders: 306700
UniProtKB/Swiss-Prot: FA8_HUMAN, P00451

Hemophilia A (HEMA) [MIM:306700]: A disorder of blood coagulation characterized by a permanent tendency

to hemorrhage. About 50% of patients have severe hemophilia resulting in frequent spontaneous bleeding into

joints, muscles and internal organs. Less severe forms are characterized by bleeding after trauma or surgery.

Note=The disease is caused by mutations affecting the gene represented in this entry. Of particular interest for

the understanding of the function of F8 is the category of CRM (cross-reacting material) positive patients

(approximately 5%) that have considerable amount of F8 in their plasma (at least 30% of normal), but the protein

is non-functional; i.e. the F8 activity is much less than the plasma protein level. CRM-reduced is another

category of patients in which the F8C antigen and activity are reduced to approximately the same level. Most

mutations are CRM negative, and probably affect the folding and stability of the protein

Selected diseases for F8 (see all 46):
About MalaCards

moderately severe hemophilia a type 2n von willebrand disease mild hemophilia a breast reconstruction

hemophilia acquired hemophilia factor viii deficiency cardiac tamponade

severe hemophilia a symptomatic form of hemophilia a in female carriers post-thrombotic syndrome acquired von willebrand syndrome

thrombophlebitis lymphangiosarcoma hemophilia b type 2a von willebrand disease

type 3 von willebrand disease von willebrand's disease intussusception hemarthrosis

Selected inferred disease relationships from the University of Copenhagen DISEASES database for F8 (see all 27):

Von Willebrand's disease Factor XI deficiency Factor VIII deficiency Hemophilia B

Thrombophilia Sarcoma Vascular disease Vascular cancer

Hemangioma Arthropathy Hepatitis Lymphangioma

Thrombocytopenia Acquired immunodeficiency syndrome Kaposi's sarcoma Hepatitis A

Carcinoma Heart disease Hypersensitivity reaction type II disease Lymphangiosarcoma

Find genes that share disorders with F8 About GenesLikeMe

Selected Novoseek inferred disease relationships for F8 gene (see all 94) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hemophilia a	97.6	760	19509468 (4), 19937483 (4), 16038719 (4), 16522813 (4) (see all 99)
von willebrand disease	94	100	8236134 (3), 1918030 (2), 12353065 (2), 2124499 (1) (see all 83)
f5f8d	86.8	19	19598067 (2), 19141160 (2), 17610559 (2), 16044454 (1) (see all 10)
coagulopathy	86.7	154	10444282 (2), 8500791 (1), 9335047 (1), 10773919 (1) (see all 99)
bleeding	79.5	342	19143924 (4), 1746594 (3), 11554946 (3), 15166918 (3) (see all 99)
hemarthrosis	75.7	10	19473418 (2), 17212730 (1), 19995408 (1), 15569163 (1) (see all 8)
bleeding tendency	75.4	11	19763351 (1), 10517121 (1), 19506363 (1), 10608727 (1) (see all 10)
hemophilia b	73.4	10	17596134 (1), 10498242 (1), 10517121 (1), 16051741 (1) (see all 8)
thrombophilia	69	27	18304616 (2), 18766260 (2), 15735796 (2), 17059421 (1) (see all 18)
inherited coagulation disorders	68.3	5	11735604 (1), 10446919 (1), 16670069 (1), 12109144 (1)

GeneTests: F8
GeneReviews: F8
Genetic Association Database (GAD): F8
Human Genome Epidemiology (HuGE) Navigator: F8 (109 documents)

Export disorders for F8 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for F8 gene, integrated from 10 sources (see all 1565):
(articles sorted by number of sources associating them with F8)

Utopia: connect your pdf to the dynamic
world of online information

Characterization of the polypeptide composition of human factor VIII:C and the nucleotide sequence and expression of the human kidney cDNA. (PubMed id 3935400)^{1, 2, 3} Truett M.A.... Ezban M. (DNA 1985)
Molecular cloning of a cDNA encoding human antihaemophilic factor. (PubMed id 6438528)^{1, 2, 3} Toole J.J....Hewick R.M. (Nature 1984)
A novel cause of mild/moderate hemophilia A: mutations scattered in the factor VIII C1 domain reduce factor VIII binding to von Willebrand factor. (PubMed id 10910910)^{1, 2, 9} Jacquemin M.... Saint-Remy J.-M.R. (Blood 2000)
Haplotypes encoding the factor VIII 1241 Glu variation, factor VIII levels and the risk of venous thrombosis. (PubMed id 16732372)^{1, 4, 9} Nossent A.Y....Rosendaal F.R. (Thromb. Haemost. 2006)
Female haemophilia A heterozygous for a de novo frameshift and a novel missense mutation of factor VIII. (PubMed id 16805874)^{1, 2, 9} Cai X.-H....Wang H.-L. (J. Thromb. Haemost. 2006)
Factor VIII gene (F8) mutations as predictors of outcome in immune tolerance induction of hemophilia A patients with high-responding inhibitors. (PubMed id 19740093)^{1, 4, 9} Coppola A....Di Minno G. (J. Thromb. Haemost. 2009)
The spectrum of the factor 8 (F8) defects in Taiwanese patients with haemophilia A. (PubMed id 18371163)^{1, 4, 9} Ma G.C....Shen M.C. (Haemophilia 2008)
The ABO blood group genotype and factor VIII levels as independent risk factors for venous thromboembolism. (PubMed id 15735796)^{1, 4, 9} Tirado I....Fontcuberta J. (Thromb. Haemost. 2005)
Intensive peri-operative use of factor VIII and the Arg593-->Cys mutation are risk factors for inhibitor development in mild/moderate hemophilia A. (PubMed id 19548904)^{1, 4, 9} Eckhardt C.L....Fijnvandraat K. (J. Thromb. Haemost. 2009)
The Italian AICE-Genetics hemophilia A database: results and correlation with clinical phenotype. (PubMed id 18387975)^{1, 4, 9} Margaglione M....Mannucci P.M. (Haematologica 2008)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 2157	HGNC: 3546	AceView: F8	Ensembl:ENSG00000185010	euGenes: HUgn2157
ECgene: F8	Kegg: 2157	H-InvDB: F8

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for F8	Pharmacogenomics, SNPs, Pathways
Wikipedia	http://en.wikipedia.org/wiki/Factor_VIII
HAMSters	http://hadb.org.uk/WebPages/Main/main.htm
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=F8[genesymbol]
SeattleSNPs	http://pga.gs.washington.edu/data/f8/

Intellectual Property for F8 gene
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Patent Information for F8 gene:
Search GeneIP for patents involving F8

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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F8 Gene

Coagulation Factor VIII, Procoagulant Component

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Pregnancy loss
Cardiac Tamponade
Hemorrhagic diseases
ABNORMAL PLATELETS
Myelofibrosis
coagulopathy
Cystic Fibrosis
Allergic Reaction
F5F8D
Purpura Thrombotic Thrombocytopenic
TRANSFUSION REACTION
Antiphospholipid Syndrome
Hypercholesterolemia
Deep vein thrombosis
AIDS
platelet disorder
disability
Cancer
Thrombocytopenia
Coagulation Factor Deficiency
Lymphoma
Cerebral Thrombosis
RENAL DISEASE
Shock
PARTIAL THROMBOPLASTIN TIME PROLONGED
ARTERIAL THROMBOSIS
Compartment Syndromes
Inflammation
Anaphylaxis
immunodeficiency
Hepatitis
Hyperhomocysteinemia
Hepatitis B
Cardiovascular Diseases
Tumors
Thrombosis
Metastasis
Sarcoma
Necrosis
molecular pathology
SUBCUTANEOUS HEMATOMA
virus infection
Viral hepatitis
Disseminated Intravascular Coagulation
Preeclampsia
Hepatitis C
Chronic Disease
APC Resistance
Autoimmune Diseases
HYPERTENSION ARTERIAL
arthropathy
Venous Thrombosis
Tetanus
atherosclerotic plaque
retinopathy
Hypothyroidism
Leukemia
Hemarthrosis
Ecchymosis
Diabetes Mellitus
Prion Diseases
Purpura Thrombocytopenic Idiopathic
HEPATOCELLULAR CARCINOMA
BLEEDING TENDENCY
Intracranial Hemorrhages
Inherited Coagulation Disorders
Myocardial Infarction
Portal vein thrombosis
von Willebrand Disease
Heart Diseases
Response Acute Phase
Microcephaly
Insulin Resistance
HIV Infections
Protein S Deficiency
Hemophilia A
Bleeding
Lymphoproliferative Disorders
Afibrinogenemia
Vitamin K Deficiency
Postpartum Hemorrhage
Menorrhagia
Glanzmann Thrombasthenia
Hematoma
Thrombophilia
STROKE
PROLONGED BLEEDING TIME
Hemophilia B
genetic disorder
platelet dysfunction
NIDDM
Thromboembolism
Thrombophlebitis
Lupus Erythematosus Systemic

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F8 Gene

Coagulation Factor VIII, Procoagulant Component

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