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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]
F8 (Coagulation Factor VIII) is a Protein Coding gene. Diseases associated with F8 include Hemophilia A and Factor Viii Deficiency. Among its related pathways are Formation of Fibrin Clot (Clotting Cascade) and Response to elevated platelet cytosolic Ca2+. Gene Ontology (GO) annotations related to this gene include oxidoreductase activity and copper ion binding. An important paralog of this gene is F5.
GeneHancer (GH) Identifier | GH Type | GH Score |
GH Sources | Gene Association Score | Total Score | TSS distance (kb) | Number of Genes Away | Size (kb) | Transcription Factor Binding Sites |
Gene Targets |
---|---|---|---|---|---|---|---|---|---|---|
GH0XJ155025 | Promoter/Enhancer | 2.2 | EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas | 600.7 | -0.7 | -717 | 3.7 | ARHGAP35 CREB1 PRDM10 REST ZNF629 IKZF1 ZNF692 POLR2A BACH1 JUND | F8 FUNDC2 lnc-F8-1 lnc-F8-2 F8A1 WASH6P PLXNA3 GAB3 IKBKG F8A2 | |
GH0XJ155022 | Promoter | 1.2 | EPDnew Ensembl | 600.4 | +6.7 | 6739 | 6 | ATF7 IKZF1 ZNF24 EP300 UBTF HMBOX1 NCOR1 CEBPG TAL1 ATF4 | F8 F8A1 TMLHE FUNDC2 lnc-F8-1 lnc-F8-2 HSALNG0140892 | |
GH0XJ154885 | Promoter | 0.7 | EPDnew Ensembl | 600.1 | +140.2 | 140239 | 3.4 | F8A1 H2AB1 MIR1184-1 F8 FUNDC2 | ||
GH0XJ154726 | Enhancer | 1.2 | FANTOM5 ENCODE dbSUPER | 2.3 | +293.8 | 293829 | 12.7 | IKZF1 JUND ZIC2 CTCF SP1 HDAC1 YY1 EGR1 CEBPB ESR1 | F8A1 F8A2 DKC1 IKBKG GAB3 EMD F8 DNASE1L1 TKTL1 MPP1 | |
GH0XJ155026 | Enhancer | 0.5 | Ensembl | 0.7 | +2.0 | 2039 | 0.2 | IKZF1 MTA2 HMBOX1 ZFP91 DPF2 VEZF1 SMARCE1 | FUNDC2 F8 lnc-F8-1 lnc-F8-2 HSALNG0140892 F8A1 |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0005507 | copper ion binding | IEA | -- |
GO:0005515 | protein binding | IPI | 7756647 |
GO:0016491 | oxidoreductase activity | IEA | -- |
GO:0046872 | metal ion binding | IEA | -- |
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0000139 | Golgi membrane | IEA | -- |
GO:0005576 | extracellular region | TAS | -- |
GO:0005615 | extracellular space | IBA | 21873635 |
GO:0005788 | endoplasmic reticulum lumen | TAS | -- |
GO:0005886 | plasma membrane | TAS | -- |
SuperPathway | Contained pathways | ||
---|---|---|---|
1 | Formation of Fibrin Clot (Clotting Cascade) | ||
2 | Transport to the Golgi and subsequent modification | ||
3 | Response to elevated platelet cytosolic Ca2+ |
.44
|
|
4 | Complement and coagulation cascades | ||
5 | Collagen chain trimerization |
Intrinsic Prothrombin Activation Pathway
.48
|
Blood Coagulation Cascade
.46
|
GO ID | Qualified GO term | Evidence | PubMed IDs |
---|---|---|---|
GO:0002576 | platelet degranulation | TAS | -- |
GO:0006888 | ER to Golgi vesicle-mediated transport | TAS | -- |
GO:0006953 | acute-phase response | IEA | -- |
GO:0007596 | blood coagulation | TAS | 8275087 |
GO:0007597 | blood coagulation, intrinsic pathway | TAS | -- |
Name | Status | Disease Links | Group | Role | Mechanism of Action | Clinical Trials |
---|---|---|---|---|---|---|
Drotrecogin alfa | Approved, Investigational, Withdrawn | Pharma | Target, multitarget, inhibitor | 0 | ||
Thrombin | Approved, Investigational | Pharma | Target, activator | 411 | ||
Copper | Approved, Investigational | Pharma | Carrier, binder | 249 | ||
Albutrepenonacog alfa | Approved | Pharma | Enzyme, substrate | 0 | ||
Anti-inhibitor coagulant complex | Approved, Investigational | Pharma | Target, Enzyme, agonist, substrate | 14 |
Name | Synonyms | Role | CAS Number | PubChem IDs | PubMed IDs |
---|
This gene was present in the common ancestor of chordates.
Organism | Taxonomy | Gene | Similarity | Type | Details |
---|---|---|---|---|---|
Chimpanzee (Pan troglodytes) |
Mammalia | F8 30 31 |
|
OneToOne | |
Dog (Canis familiaris) |
Mammalia | F8 30 31 |
|
OneToOne | |
Cow (Bos Taurus) |
Mammalia | F8 30 31 |
|
OneToOne | |
Mouse (Mus musculus) |
Mammalia | F8 30 17 31 |
|
OneToOne | |
Rat (Rattus norvegicus) |
Mammalia | F8 30 |
|
||
Platypus (Ornithorhynchus anatinus) |
Mammalia | F8 31 |
|
OneToOne | |
Oppossum (Monodelphis domestica) |
Mammalia | F8 31 |
|
OneToOne | |
Chicken (Gallus gallus) |
Aves | F8 31 |
|
OneToOne | |
Lizard (Anolis carolinensis) |
Reptilia | F8 31 |
|
OneToOne | |
Zebrafish (Danio rerio) |
Actinopterygii | f8 31 |
|
OneToOne | |
Sea Squirt (Ciona savignyi) |
Ascidiacea | CSA.2640 31 |
|
OneToMany |
SNP ID | Clinical significance and condition | Chr 0X pos | Variation | AA Info | Type |
---|---|---|---|---|---|
503494 | Pathogenic: Mild hemophilia A | 154,947,224(-) | GAAAAAAAAAAAAA/G | INTRON_VARIANT | |
618101 | Pathogenic: not provided | 154,966,059(-) | CTG/C | FRAMESHIFT_VARIANT | |
626933 | Pathogenic: Hereditary factor IX deficiency disease | 154,863,110(-) | T/C | MISSENSE_VARIANT | |
626935 | Pathogenic: Hereditary factor IX deficiency disease | 154,861,755(-) | A/G | MISSENSE_VARIANT | |
626964 | Likely Pathogenic: Hereditary factor IX deficiency disease | 154,966,623(-) | A/AT | FRAMESHIFT_VARIANT |
Variant ID | Type | Subtype | PubMed ID |
---|---|---|---|
esv29972 | CNV | gain | 17803354 |
esv33784 | CNV | gain+loss | 17666407 |
esv3577568 | CNV | gain | 25503493 |
esv3577569 | CNV | gain | 25503493 |
nsv1076287 | CNV | deletion | 25765185 |
nsv1132792 | CNV | duplication | 24896259 |
Disorder | Aliases | PubMed IDs |
---|---|---|
hemophilia a |
|
|
factor viii deficiency |
|
|
hemophilia b |
|
|
hemophilia |
|
|
hemarthrosis |
|