F8
coagulation factor VIII
Basic information
Region (hg38): X:154835787-155026940
Previous symbols: [ "F8C" ]
Links
Phenotypes
GenCC
Source:
- hemophilia A (Strong), mode of inheritance: XL
- severe hemophilia A (Supportive), mode of inheritance: XL
- moderately severe hemophilia A (Supportive), mode of inheritance: XL
- mild hemophilia A (Supportive), mode of inheritance: XL
- symptomatic form of hemophilia A in female carriers (Supportive), mode of inheritance: XL
- hemophilia A (Definitive), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hemophilia A; Thrombophilia 13, X-linked, due to factor VIII defect | XL | Hematologic; Pharmacogenomic | In people with Hemophilia A, plasma-derived factor VIII concentrate and/or desmopressin can be used to treat/prevent bleeding, and gene therapy has been described as beneficial; Other considerations may be beneficial in specific circumstances, such as in postpartum females; Certain circumstances should be avoided or need to be specifically managed, such as circumcision, high-risk activities, and medications such as aspirin; Individuals with Thrombophilia 13 may be at increased risk of blood clots, and awareness may allow medical management (eg, with heparin-related agents and warfarin) and prompt management of sequelae | Hematologic | 13739554; 2987704; 3012775; 3035554; 3097553; 3338800; 3131627; 2833855; 2835904; 3139545; 1688823; 2123300; 1357455; 8275087; 8281136; 8259143; 7662970; 3893256; 8644728; 8968748; 9042915; 11023529; 11396445; 11857744; 12907007; 16786531; 16551972; 18691168; 18217193; 20301578; 21056901; 22507546; 22621702; 22639879; 22866674; 23005041; 23025325; 23047359; 23067060; 29224506; 33275657 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary factor VIII deficiency disease (388 variants)
- not provided (192 variants)
- Hereditary factor IX deficiency disease (57 variants)
- Inborn genetic diseases (50 variants)
- not specified (35 variants)
- Thrombophilia, X-linked, due to factor 8 defect (35 variants)
- F8-related condition (27 variants)
- Abnormality of coagulation (9 variants)
- Hereditary factor VIII deficiency disease;Thrombophilia, X-linked, due to factor 8 defect (8 variants)
- Thrombophilia, X-linked, due to factor 8 defect;Hereditary factor VIII deficiency disease (6 variants)
- Cerebral palsy (1 variants)
- Abnormal bleeding (1 variants)
- Hemophilia A, FVIII Deficiency (1 variants)
- Hemorrhage (1 variants)
- Mild hemophilia A (1 variants)
- See cases (1 variants)
- FACTOR VIII (OKAYAMA) (1 variants)
- FACTOR VIII (EAST HARTFORD) (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the F8 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 21 | 34 | ||||
| missense | 78 | 135 | 134 | 16 | 369 | |
| nonsense | 38 | 43 | ||||
| start loss | 1 | |||||
| frameshift | 44 | 17 | 61 | |||
| inframe indel | 2 | |||||
| splice donor/acceptor (+/-2bp) | 14 | |||||
| splice region ? | 6 | 1 | 1 | 8 | ||
| non coding ? | 28 | 15 | 20 | 68 | ||
| Total | 170 | 167 | 170 | 52 | 33 |
Highest pathogenic variant AF is 0.000168
Variants in F8
This is a list of pathogenic ClinVar variants found in the F8 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| X-154835866-A-G | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154835925-C-T | Hereditary factor VIII deficiency disease | Benign (Jan 12, 2018) | ||
| X-154836181-C-A | Hereditary factor VIII deficiency disease | Benign (Jan 13, 2018) | ||
| X-154836218-T-C | Hereditary factor VIII deficiency disease | Likely benign (Jan 13, 2018) | ||
| X-154836235-T-A | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154836383-C-T | Hereditary factor VIII deficiency disease | Benign (Jan 12, 2018) | ||
| X-154836422-C-G | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 12, 2018) | ||
| X-154836431-T-C | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 12, 2018) | ||
| X-154836580-G-T | Hereditary factor VIII deficiency disease | Uncertain significance (Apr 27, 2017) | ||
| X-154836596-G-A | Hereditary factor VIII deficiency disease | Benign (Jan 13, 2018) | ||
| X-154836605-T-C | Hereditary factor VIII deficiency disease | Likely benign (Jan 12, 2018) | ||
| X-154836622-T-C | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 12, 2018) | ||
| X-154836682-C-T | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154836689-A-C | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154836735-T-C | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154837137-C-T | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154837171-C-T | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154837175-TGA-T | Hemophilia A, FVIII Deficiency | Uncertain significance (Jun 14, 2016) | ||
| X-154837309-G-T | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154837421-C-T | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 12, 2018) | ||
| X-154837519-G-A | Hereditary factor VIII deficiency disease | Uncertain significance (Jan 13, 2018) | ||
| X-154837541-C-A | Likely pathogenic (Jun 23, 2020) | |||
| X-154837567-C-T | Hereditary factor VIII deficiency disease | Likely benign (Jan 13, 2018) | ||
| X-154837568-G-A | Hereditary factor VIII deficiency disease | Benign (Nov 11, 2019) | ||
| X-154837622-C-T | Inborn genetic diseases | Likely pathogenic (Nov 10, 2015) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| F8 | protein_coding | protein_coding | ENST00000360256 | 26 | 191153 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 1.00 | 1.79e-10 | 125740 | 1 | 3 | 125744 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.47 | 642 | 844 | 0.761 | 0.0000606 | 15592 |
| Missense in Polyphen | 85 | 273.66 | 0.31061 | 4952 | ||
| Synonymous | 1.37 | 274 | 304 | 0.900 | 0.0000219 | 4421 |
| Loss of Function | 7.55 | 2 | 70.4 | 0.0284 | 0.00000525 | 1274 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000366 | 0.0000366 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000625 | 0.0000462 |
| European (Non-Finnish) | 0.0000245 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Factor VIII, along with calcium and phospholipid, acts as a cofactor for F9/factor IXa when it converts F10/factor X to the activated form, factor Xa.;
- Disease
- DISEASE: 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. {ECO:0000269|PubMed:10215414, ECO:0000269|PubMed:10338101, ECO:0000269|PubMed:10404764, ECO:0000269|PubMed:10408784, ECO:0000269|PubMed:10554831, ECO:0000269|PubMed:10612839, ECO:0000269|PubMed:10691849, ECO:0000269|PubMed:10800171, ECO:0000269|PubMed:10886198, ECO:0000269|PubMed:10896236, ECO:0000269|PubMed:10910910, ECO:0000269|PubMed:10910913, ECO:0000269|PubMed:11298607, ECO:0000269|PubMed:11341489, ECO:0000269|PubMed:11410838, ECO:0000269|PubMed:11442643, ECO:0000269|PubMed:11442647, ECO:0000269|PubMed:11554935, ECO:0000269|PubMed:11748850, ECO:0000269|PubMed:11857744, ECO:0000269|PubMed:11858487, ECO:0000269|PubMed:12195713, ECO:0000269|PubMed:12199686, ECO:0000269|PubMed:12203998, ECO:0000269|PubMed:12325022, ECO:0000269|PubMed:12351418, ECO:0000269|PubMed:12406074, ECO:0000269|PubMed:12614369, ECO:0000269|PubMed:12871415, ECO:0000269|PubMed:12930394, ECO:0000269|PubMed:1301194, ECO:0000269|PubMed:1301932, ECO:0000269|PubMed:1301960, ECO:0000269|PubMed:1349567, ECO:0000269|PubMed:1356412, ECO:0000269|PubMed:15682412, ECO:0000269|PubMed:15810915, ECO:0000269|PubMed:1639429, ECO:0000269|PubMed:16805874, ECO:0000269|PubMed:18184865, ECO:0000269|PubMed:1851341, ECO:0000269|PubMed:1908096, ECO:0000269|PubMed:1908817, ECO:0000269|PubMed:1973901, ECO:0000269|PubMed:2104766, ECO:0000269|PubMed:2105106, ECO:0000269|PubMed:2105906, ECO:0000269|PubMed:2106480, ECO:0000269|PubMed:2107542, ECO:0000269|PubMed:21371196, ECO:0000269|PubMed:2495245, ECO:0000269|PubMed:2498882, ECO:0000269|PubMed:2499363, ECO:0000269|PubMed:2506948, ECO:0000269|PubMed:2510835, ECO:0000269|PubMed:25550078, ECO:0000269|PubMed:26278069, ECO:0000269|PubMed:2833855, ECO:0000269|PubMed:2835904, ECO:0000269|PubMed:3012775, ECO:0000269|PubMed:3122181, ECO:0000269|PubMed:7579394, ECO:0000269|PubMed:7759074, ECO:0000269|PubMed:7794769, ECO:0000269|PubMed:8322269, ECO:0000269|PubMed:8449505, ECO:0000269|PubMed:8639447, ECO:0000269|PubMed:8644728, ECO:0000269|PubMed:8759905, ECO:0000269|PubMed:9029040, ECO:0000269|PubMed:9326186, ECO:0000269|PubMed:9341862, ECO:0000269|PubMed:9450898, ECO:0000269|PubMed:9452104, ECO:0000269|PubMed:9569180, ECO:0000269|PubMed:9569189, ECO:0000269|PubMed:9603440, ECO:0000269|PubMed:9792405, ECO:0000269|PubMed:9829908, ECO:0000269|PubMed:9886318}. 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.;
- Pathway
- Complement and coagulation cascades - Homo sapiens (human);Aminocaproic Acid Action Pathway;Tranexamic Acid Action Pathway;Urokinase Action Pathway;Reteplase Action Pathway;Streptokinase Action Pathway;Tenecteplase Action Pathway;Alteplase Action Pathway;Anistreplase Action Pathway;Aprotinin Action Pathway;Phenindione Action Pathway;Dicoumarol Action Pathway;Warfarin Action Pathway;Acenocoumarol Action Pathway;Coagulation ;Bivalirudin Action Pathway;Argatroban Action Pathway;Ardeparin Action Pathway;Heparin Action Pathway;Fondaparinux Action Pathway;Enoxaparin Action Pathway;Phenprocoumon Action Pathway;Dicumarol Action Pathway;Ximelagatran Action Pathway;Lepirudin Action Pathway;Blood Clotting Cascade;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Complement and Coagulation Cascades;Vesicle-mediated transport;Membrane Trafficking;intrinsic prothrombin activation pathway;Post-translational protein modification;Metabolism of proteins;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Cargo concentration in the ER;Intrinsic Pathway of Fibrin Clot Formation;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Hemostasis;Common Pathway of Fibrin Clot Formation;Formation of Fibrin Clot (Clotting Cascade);COPII-mediated vesicle transport;ER to Golgi Anterograde Transport
(Consensus)
Recessive Scores
- pRec
- 0.829
Intolerance Scores
- loftool
- 0.00158
- rvis_EVS
- -0.75
- rvis_percentile_EVS
- 13.77
Haploinsufficiency Scores
- pHI
- 0.0975
- hipred
- N
- hipred_score
- 0.455
- ghis
- 0.430
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.619
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- F8
- Phenotype
- immune system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); homeostasis/metabolism phenotype;
Zebrafish Information Network
- Gene name
- f8
- Affected structure
- thrombocyte
- Phenotype tag
- abnormal
- Phenotype quality
- distributed
Gene ontology
- Biological process
- platelet degranulation;endoplasmic reticulum to Golgi vesicle-mediated transport;acute-phase response;blood coagulation;blood coagulation, intrinsic pathway;platelet activation;COPII vesicle coating;oxidation-reduction process
- Cellular component
- Golgi membrane;extracellular region;extracellular space;endoplasmic reticulum lumen;plasma membrane;COPII-coated ER to Golgi transport vesicle;platelet alpha granule lumen;endoplasmic reticulum-Golgi intermediate compartment membrane
- Molecular function
- copper ion binding;protein binding;oxidoreductase activity