F5

coagulation factor V

Basic information

Region (hg38): 1:169511951-169586588

Links

ENSG00000198734 ∙ NCBI:2153 ∙ OMIM:612309 ∙ HGNC:3542 ∙ Uniprot:P12259 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombophilia due to activated protein C resistance (Strong), mode of inheritance: AD
• congenital factor V deficiency (Supportive), mode of inheritance: AR
• East Texas bleeding disorder (Supportive), mode of inheritance: AD
• thrombophilia due to activated protein C resistance (Strong), mode of inheritance: AD
• thrombophilia due to activated protein C resistance (Definitive), mode of inheritance: AD
• congenital factor V deficiency (Definitive), mode of inheritance: AR
• congenital factor V deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombophilia due to activated protein C resistance; Factor V deficiency	AD/AR	Hematologic; Pharmacogenomic	In Thrombophilia due to activated protein C resistance, surveillance and treatment (including preventive measures in some individuals) may reduce morbidity; The condition may result in recurrent pregnancy loss, and awareness may help management of pregnancy; Precautions should be taken regarding the avoidance of certain medications (eg, estrogen-containing OCPs); Individuals with Factor V deficiency can suffer from bleeding diatheses of varying severity, and preventive measures, as well as prompt treatment (eg, with fresh frozen plasma or platelet transfusion in instances of severe bleeding) related to bleeding episodes can be beneficial	Hematologic	20293060; 13194849; 13575936; 1239529; 694421; 6348091; 6479988; 8430067; 7803250; 8108421; 8164741; 7910348; 7969326; 8049422; 7911872; 7911873; 7989612; 7586244; 7877648; 8616100; 8627449; 8639453; 8815565; 9207293; 9245936; 9010145; 9372726; 9518910; 9577282; 9877047; 9576178; 9846775; 9734642; 9459326; 9462312; 9488630; 9454742; 10233438; 10477778; 10066036; 10328130; 9878639; 10507841; 10666427; 11001884; 11018168; 11167765; 10943572; 11532625; 11435304; 11781258; 11859850; 12138364; 12393490; 12393635; 14617013; 15534175; 15293282; 14673478; 14996674; 16113779; 16551553; 16707754; 16606808; 19531787; 21292261; 21320286; 21730834; 21777354; 22251029; 22758216; 22888854; 22990475; 23034579
Variants in F5 may interact with variants in other genes, such as F2 and MTHFR, to result in susceptibility to hematologic manifestations

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the F5 gene.

• Congenital factor V deficiency (29 variants)
• Factor V deficiency (7 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the F5 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			10	314	1	325
missense	4	4	220	41	4	273
nonsense	17	5				22
start loss						0
frameshift	15	8	1			24
inframe indel			4	1		5
splice donor/acceptor (+/-2bp)		10				10
splice region			3	20	3	26
non coding			40	111	95	246
Total	36	27	275	467	100

Highest pathogenic variant AF is 0.0000461

Variants in F5

This is a list of pathogenic ClinVar variants found in the F5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
1-169511962-G-T		Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Factor V deficiency • Budd-Chiari syndrome	Uncertain significance (Jan 12, 2018)
1-169511985-C-G		Budd-Chiari syndrome • Factor V deficiency • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect	Benign/Likely benign (Jan 12, 2018)
1-169512165-G-A		Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Factor V deficiency	Uncertain significance (Jan 12, 2018)
1-169512260-C-G		Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Factor V deficiency • Thrombophilia due to thrombin defect	Uncertain significance (Jan 12, 2018)
1-169512276-C-T		Thrombophilia due to thrombin defect • Budd-Chiari syndrome • Factor V deficiency	Conflicting classifications of pathogenicity (Jan 13, 2018)
1-169512374-A-G		Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Factor V deficiency	Uncertain significance (Jan 12, 2018)
1-169512401-G-A		Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Factor V deficiency • Thrombophilia due to thrombin defect	Uncertain significance (Jan 13, 2018)
1-169512456-C-T		Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Budd-Chiari syndrome • Factor V deficiency	Uncertain significance (Jan 13, 2018)
1-169512493-T-G		Factor V deficiency • Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Budd-Chiari syndrome	Benign/Likely benign (May 11, 2021)
1-169512533-C-A		Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Budd-Chiari syndrome • Factor V deficiency	Uncertain significance (Jan 12, 2018)
1-169512537-T-C		Budd-Chiari syndrome • Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Factor V deficiency	Uncertain significance (Jan 12, 2018)
1-169512598-A-C		Factor V deficiency • Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect	Uncertain significance (Jan 13, 2018)
1-169512614-C-A		Budd-Chiari syndrome • Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Factor V deficiency	Uncertain significance (Jan 13, 2018)
1-169512700-T-C		Budd-Chiari syndrome • Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Factor V deficiency	Uncertain significance (Jan 12, 2018)
1-169512712-G-A		Factor V deficiency • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Budd-Chiari syndrome	Benign/Likely benign (May 11, 2021)
1-169512782-G-A		Thrombophilia due to activated protein C resistance • Factor V deficiency • Budd-Chiari syndrome • Thrombophilia due to thrombin defect	Uncertain significance (Jan 15, 2018)
1-169512825-A-G		Budd-Chiari syndrome • Thrombophilia due to thrombin defect • Thrombophilia due to activated protein C resistance • Factor V deficiency	Conflicting classifications of pathogenicity (Jan 13, 2018)
1-169512877-A-T		Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Budd-Chiari syndrome • Factor V deficiency	Benign/Likely benign (May 12, 2021)
1-169512880-C-T		Budd-Chiari syndrome • Factor V deficiency • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect	Uncertain significance (Mar 30, 2018)
1-169512881-G-A		Thrombophilia due to thrombin defect • Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Factor V deficiency	Uncertain significance (Jan 12, 2018)
1-169512909-C-T		Thrombophilia due to activated protein C resistance • Factor V deficiency • Thrombophilia due to thrombin defect • Budd-Chiari syndrome	Uncertain significance (Jan 15, 2018)
1-169513012-T-A		Factor V deficiency • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Budd-Chiari syndrome	Uncertain significance (Apr 27, 2017)
1-169513023-C-T		Factor V deficiency • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Budd-Chiari syndrome	Conflicting classifications of pathogenicity (Jan 12, 2018)
1-169513056-T-G		Budd-Chiari syndrome • Thrombophilia due to activated protein C resistance • Thrombophilia due to thrombin defect • Factor V deficiency	Uncertain significance (Jan 13, 2018)
1-169513067-G-A		Thrombophilia due to activated protein C resistance • Budd-Chiari syndrome • Factor V deficiency • Thrombophilia due to thrombin defect	Benign/Likely benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
F5	protein_coding	protein_coding	ENST00000367797	25	72423

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.92e-15	1.00	125652	0	96	125748	0.000382

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.462	1085	1.13e+3	0.961	0.0000581	14744
Missense in Polyphen		313	396.97	0.78846		5279
Synonymous	-0.178	411	406	1.01	0.0000214	4179
Loss of Function	5.12	41	94.7	0.433	0.00000500	1150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000780	0.000778
Ashkenazi Jewish	0.000696	0.000695
East Asian	0.000326	0.000326
Finnish	0.000647	0.000647
European (Non-Finnish)	0.000291	0.000290
Middle Eastern	0.000326	0.000326
South Asian	0.000392	0.000392
Other	0.000817	0.000815

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.
• Disease: DISEASE: Factor V deficiency (FA5D) [MIM:227400]: A blood coagulation disorder leading to a hemorrhagic diathesis known as parahemophilia. {ECO:0000269|PubMed:10942390, ECO:0000269|PubMed:12393490}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Thrombophilia due to activated protein C resistance (THPH2) [MIM:188055]: A hemostatic disorder due to defective degradation of factor V by activated protein C. It is characterized by a poor anticoagulant response to activated protein C resulting in tendency to thrombosis. {ECO:0000269|PubMed:10391209, ECO:0000269|PubMed:10942390, ECO:0000269|PubMed:11435304, ECO:0000269|PubMed:11858490, ECO:0000269|PubMed:14617013, ECO:0000269|PubMed:14695241, ECO:0000269|PubMed:16710414, ECO:0000269|PubMed:8164741, ECO:0000269|PubMed:9454742}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Budd-Chiari syndrome (BDCHS) [MIM:600880]: A syndrome caused by obstruction of hepatic venous outflow involving either the hepatic veins or the terminal segment of the inferior vena cava. Obstructions are generally caused by thrombosis and lead to hepatic congestion and ischemic necrosis. Clinical manifestations observed in the majority of patients include hepatomegaly, right upper quadrant pain and abdominal ascites. Budd-Chiari syndrome is associated with a combination of disease states including primary myeloproliferative syndromes and thrombophilia due to factor V Leiden, protein C deficiency and antithrombin III deficiency. Budd-Chiari syndrome is a rare but typical complication in patients with polycythemia vera. {ECO:0000269|PubMed:9245936}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Ischemic stroke (ISCHSTR) [MIM:601367]: A stroke is an acute neurologic event leading to death of neural tissue of the brain and resulting in loss of motor, sensory and/or cognitive function. Ischemic strokes, resulting from vascular occlusion, is considered to be a highly complex disease consisting of a group of heterogeneous disorders with multiple genetic and environmental risk factors. {ECO:0000269|PubMed:15534175}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Pregnancy loss, recurrent, 1 (RPRGL1) [MIM:614389]: A common complication of pregnancy, resulting in spontaneous abortion before the fetus has reached viability. The term includes all miscarriages from the time of conception until 24 weeks of gestation. Recurrent pregnancy loss is defined as 3 or more consecutive spontaneous abortions. {ECO:0000269|PubMed:11018168}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
• 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 phosphorylation;Post-translational protein modification;Metabolism of proteins;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Cargo concentration in the ER;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;extrinsic prothrombin activation pathway (Consensus)

Intolerance Scores

• loftool: 0.0863
• rvis_EVS: 3.23
• rvis_percentile_EVS: 99.38

Haploinsufficiency Scores

• pHI: 0.174
• hipred: N
• hipred_score: 0.233
• ghis: 0.406

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.551

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

• Gene name: F5
• Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary 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); 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); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: platelet degranulation;endoplasmic reticulum to Golgi vesicle-mediated transport;blood coagulation;blood circulation;post-translational protein modification;cellular protein metabolic process;COPII vesicle coating
• Cellular component: Golgi membrane;extracellular region;extracellular space;endoplasmic reticulum lumen;plasma membrane;membrane;COPII-coated ER to Golgi transport vesicle;platelet alpha granule lumen;endoplasmic reticulum-Golgi intermediate compartment membrane;extracellular vesicle
• Molecular function: copper ion binding;protein binding