F9
coagulation factor IX, the group of Gla domain containing
Basic information
Region (hg38): X:139530739-139563459
Links
Phenotypes
GenCC
Source:
- severe hemophilia B (Supportive), mode of inheritance: XL
- moderately severe hemophilia B (Supportive), mode of inheritance: XL
- mild hemophilia B (Supportive), mode of inheritance: XL
- symptomatic form of hemophilia B in female carriers (Supportive), mode of inheritance: XL
- hemophilia B (Strong), mode of inheritance: XL
- hemophilia B (Definitive), mode of inheritance: XL
- thrombophilia, X-linked, due to factor 9 defect (Limited), mode of inheritance: XL
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Hemophilia B; Thrombophilia, X-linked, due to factor IX defect; Warfarin sensitivity, X-linked | XL | Hematologic; Pharmacogenomic | In Hemophilia B, recombinant or plasma-derived factor IX concentrate can be effective for prevention/treatment of bleeding episodes, 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; In X-linked thrombophilia, preventive measures related to thrombophilia, as well as early recognition and treatment of manifestations such as deep venous thromboses, may reduce morbidity | Hematologic | 14920537; 12997790; 4163943; 4972271; 5781711; 5450691; 734633; 7062952; 6142993; 3001143; 2907054; 3219291; 2841226; 2570235; 1768766; 1873221; 1601420; 8392713; 8352232; 8096443; 8304338; 8594556; 8833911; 9016521; 9233593; 10845896; 11122385; 11328285; 18349091; 18624978; 19251637; 19815722; 19846852; 20301668; 21056901; 29211678; 36812434 |
ClinVar
This is a list of variants' phenotypes submitted to
- Hereditary_factor_IX_deficiency_disease (484 variants)
- Thrombophilia,_X-linked,_due_to_factor_9_defect (344 variants)
- not_specified (88 variants)
- not_provided (76 variants)
- F9-related_disorder (30 variants)
- Warfarin_sensitivity,_X-linked (23 variants)
- Hereditary_factor_VIII_deficiency_disease (20 variants)
- Inborn_genetic_diseases (7 variants)
- Abnormality_of_coagulation (4 variants)
- Hemophilia_b(m) (2 variants)
- Thrombus (1 variants)
- Reduced_factor_IX_activity (1 variants)
- FACTOR_IX,_DNA_POLYMORPHISM (1 variants)
- FACTOR_IX_POLYMORPHISM (1 variants)
- haemophilia_B (1 variants)
- F9_POLYMORPHISM (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the F9 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000133.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 119 | 17 | 148 | |||
| missense | 101 | 92 | 86 | 15 | 302 | |
| nonsense | 31 | 35 | ||||
| start loss | 0 | |||||
| frameshift | 18 | 22 | ||||
| splice donor/acceptor (+/-2bp) | 14 | 16 | ||||
| Total | 167 | 104 | 93 | 134 | 25 |
Highest pathogenic variant AF is 0.0000302563
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| F9 | protein_coding | protein_coding | ENST00000218099 | 8 | 32701 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.998 | 0.00224 | 125151 | 0 | 1 | 125152 | 0.00000400 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.18 | 93 | 174 | 0.535 | 0.0000128 | 3042 |
| Missense in Polyphen | 18 | 73.466 | 0.24501 | 1278 | ||
| Synonymous | -1.25 | 73 | 60.7 | 1.20 | 0.00000451 | 843 |
| Loss of Function | 3.92 | 0 | 17.9 | 0.00 | 0.00000153 | 284 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000123 | 0.00000885 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.00 | 0.00 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Factor IX is a vitamin K-dependent plasma protein that participates in the intrinsic pathway of blood coagulation by converting factor X to its active form in the presence of Ca(2+) ions, phospholipids, and factor VIIIa. {ECO:0000269|PubMed:1730085, ECO:0000269|PubMed:19846852, ECO:0000269|PubMed:20121197, ECO:0000269|PubMed:20121198, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:8295821}.;
- Disease
- DISEASE: Hemophilia B (HEMB) [MIM:306900]: An X-linked blood coagulation disorder characterized by a permanent tendency to hemorrhage, due to factor IX deficiency. It is phenotypically similar to hemophilia A, but patients present with fewer symptoms. Many patients are asymptomatic until the hemostatic system is stressed by surgery or trauma. {ECO:0000269|PubMed:10094553, ECO:0000269|PubMed:10698280, ECO:0000269|PubMed:11122099, ECO:0000269|PubMed:12588353, ECO:0000269|PubMed:12604421, ECO:0000269|PubMed:1346975, ECO:0000269|PubMed:1615485, ECO:0000269|PubMed:1902289, ECO:0000269|PubMed:1958666, ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:2339358, ECO:0000269|PubMed:2372509, ECO:0000269|PubMed:2472424, ECO:0000269|PubMed:25251685, ECO:0000269|PubMed:25470321, ECO:0000269|PubMed:2592373, ECO:0000269|PubMed:2713493, ECO:0000269|PubMed:2714791, ECO:0000269|PubMed:2738071, ECO:0000269|PubMed:2753873, ECO:0000269|PubMed:2773937, ECO:0000269|PubMed:2775660, ECO:0000269|PubMed:3009023, ECO:0000269|PubMed:3243764, ECO:0000269|PubMed:3401602, ECO:0000269|PubMed:3790720, ECO:0000269|PubMed:6603618, ECO:0000269|PubMed:7981722, ECO:0000269|PubMed:8076946, ECO:0000269|PubMed:8199596, ECO:0000269|PubMed:8257988, ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:8680410, ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9222764, ECO:0000269|PubMed:9452115, ECO:0000269|PubMed:9590153, ECO:0000269|PubMed:9600455}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Note=Mutations in position 43 (Oxford-3, San Dimas) and 46 (Cambridge) prevents cleavage of the propeptide (PubMed:12588353, PubMed:2738071, PubMed:3009023, PubMed:8295821, PubMed:9169594, PubMed:9600455, PubMed:25251685). Mutation in position 93 (Alabama) probably fails to bind to cell membranes (PubMed:3790720). Mutation in position 191 (Chapel-Hill) or in position 226 (Nagoya or Hilo) prevent cleavage of the activation peptide (PubMed:6603618, PubMed:8076946, PubMed:12588353, PubMed:2162822, PubMed:25251685, PubMed:2713493). {ECO:0000269|PubMed:12588353, ECO:0000269|PubMed:2162822, ECO:0000269|PubMed:25251685, ECO:0000269|PubMed:2713493, ECO:0000269|PubMed:2738071, ECO:0000269|PubMed:3009023, ECO:0000269|PubMed:3790720, ECO:0000269|PubMed:6603618, ECO:0000269|PubMed:8076946, ECO:0000269|PubMed:8295821, ECO:0000269|PubMed:9169594, ECO:0000269|PubMed:9600455}.; DISEASE: Thrombophilia, X-linked, due to factor IX defect (THPH8) [MIM:300807]: A hemostatic disorder characterized by a tendency to thrombosis. {ECO:0000269|PubMed:19846852}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Complement and coagulation cascades - Homo sapiens (human);Warfarin Pathway, Pharmacodynamics;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;platelet amyloid precursor protein pathway;intrinsic prothrombin activation pathway;Post-translational protein modification;Metabolism of proteins;Gamma-carboxylation of protein precursors;Removal of aminoterminal propeptides from gamma-carboxylated proteins;Gamma-carboxylation, transport, and amino-terminal cleavage of proteins;Gamma carboxylation, hypusine formation and arylsulfatase activation;Extrinsic Pathway of Fibrin Clot Formation;Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade)
(Consensus)
Recessive Scores
- pRec
- 0.572
Intolerance Scores
- loftool
- rvis_EVS
- -0.03
- rvis_percentile_EVS
- 51.66
Haploinsufficiency Scores
- pHI
- 0.347
- hipred
- Y
- hipred_score
- 0.749
- ghis
- 0.423
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.697
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- F9
- Phenotype
- homeostasis/metabolism phenotype; immune system phenotype; embryo 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); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype;
Gene ontology
- Biological process
- proteolysis;endoplasmic reticulum to Golgi vesicle-mediated transport;blood coagulation;blood coagulation, intrinsic pathway;zymogen activation
- Cellular component
- extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi lumen;plasma membrane;extracellular exosome
- Molecular function
- endopeptidase activity;serine-type endopeptidase activity;calcium ion binding;protein binding