F7

coagulation factor VII, the group of Gla domain containing

Basic information

Region (hg38): 13:113105788-113120685

Links

ENSG00000057593 ∙ NCBI:2155 ∙ OMIM:613878 ∙ HGNC:3544 ∙ Uniprot:P08709 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• congenital factor VII deficiency (Supportive), mode of inheritance: AR
• congenital factor VII deficiency (Definitive), mode of inheritance: AR
• factor VII deficiency (Definitive), mode of inheritance: AR
• congenital factor VII deficiency (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Factor VII deficiency	AR	Hematologic; Pharmacogenomic	Individuals can suffer from bleeding diatheses of varying severity, and preventive measures and prompt treatment (including with factor replacement therapy) related to bleeding episodes can be beneficial; Precautions should be taken related to certain agents that may provoke/worsen bleeding risk	Hematologic	7919338; 7981691; 8652821; 8883260; 9680360; 11091194; 10984565; 11129332; 10862079; 11225604; 11139238; 11260055; 12181036; 11529858; 22188821; 22327818; 22356641; 22628013; 22684392; 22845882; 22873696; 22974900

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the F7 gene.

• Congenital factor VII deficiency (3 variants)
• not provided (3 variants)
• Factor VII deficiency (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the F7 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			4	7	3	14
missense		32	58	5	1	96
nonsense	4	4				8
start loss			1			1
frameshift	2	3	1			6
inframe indel		2				2
splice donor/acceptor (+/-2bp)	1	3				4
splice region		2	2	2	1	7
non coding		2	47	12	12	73
Total	7	46	111	24	16

Highest pathogenic variant AF is 0.0000197

Variants in F7

This is a list of pathogenic ClinVar variants found in the F7 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-113105794-C-A		Factor VII deficiency • Congenital factor VII deficiency	Uncertain significance (Jan 12, 2018)
13-113105798-T-C		F7-related disorder	Likely benign (Apr 04, 2019)
13-113105812-A-C		Factor VII deficiency	Likely pathogenic (Feb 01, 2019)
13-113105815-C-T		Factor VII deficiency • Congenital factor VII deficiency	Uncertain significance (Jan 01, 2020)
13-113105843-T-C			Uncertain significance (Feb 21, 2022)
13-113105879-T-C		Factor VII deficiency	Pathogenic (Apr 01, 1998)
13-113105905-G-A		Myocardial infarction, susceptibility to;Congenital factor VII deficiency	Likely pathogenic (-)
13-113105909-C-T		Factor VII deficiency • not specified • Myocardial infarction, susceptibility to;Congenital factor VII deficiency • Congenital factor VII deficiency	Likely benign (Nov 22, 2021)
13-113105910-G-A			Likely pathogenic (May 01, 2017)
13-113105913-C-T		Factor VII deficiency	Benign/Likely benign (Mar 30, 2018)
13-113105914-G-A		not specified • Factor VII deficiency	Benign (Sep 07, 2018)
13-113106101-G-A			Benign (Jun 18, 2021)
13-113106842-C-T		Congenital factor VII deficiency	Uncertain significance (May 06, 2024)
13-113106846-C-T		Factor VII deficiency	Benign (Jul 20, 2017)
13-113106850-G-T		Inborn genetic diseases	Uncertain significance (Aug 08, 2023)
13-113106865-G-A		Inborn genetic diseases	Uncertain significance (May 23, 2023)
13-113106888-G-A		Factor VII deficiency	Benign/Likely benign (Mar 02, 2018)
13-113106910-G-A		Congenital factor VII deficiency	Likely pathogenic (May 19, 2023)
13-113106921-A-T		Factor VII deficiency	Uncertain significance (Jan 12, 2018)
13-113107199-C-T			Benign (Nov 11, 2018)
13-113110704-G-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)
13-113110704-GA-G		Myocardial infarction, susceptibility to;Congenital factor VII deficiency	Likely pathogenic (-)
13-113110709-A-C		Factor VII deficiency	Likely benign (Apr 28, 2021)
13-113110711-C-A		Congenital factor VII deficiency	Likely pathogenic (Feb 23, 2022)
13-113110713-C-T		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
F7	protein_coding	protein_coding	ENST00000375581	9	14891

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000135	0.960	125537	0	208	125745	0.000827

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.320	289	305	0.948	0.0000202	3002
Missense in Polyphen		106	123.31	0.8596		1246
Synonymous	1.22	116	134	0.866	0.00000951	942
Loss of Function	1.89	11	20.2	0.545	0.00000105	221

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00193	0.00193
Ashkenazi Jewish	0.000796	0.000794
East Asian	0.000707	0.000707
Finnish	0.000232	0.000231
European (Non-Finnish)	0.000945	0.000941
Middle Eastern	0.000707	0.000707
South Asian	0.000294	0.000294
Other	0.000653	0.000652

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Initiates the extrinsic pathway of blood coagulation. Serine protease that circulates in the blood in a zymogen form. Factor VII is converted to factor VIIa by factor Xa, factor XIIa, factor IXa, or thrombin by minor proteolysis. In the presence of tissue factor and calcium ions, factor VIIa then converts factor X to factor Xa by limited proteolysis. Factor VIIa will also convert factor IX to factor IXa in the presence of tissue factor and calcium.
• Disease: DISEASE: Factor VII deficiency (FA7D) [MIM:227500]: A hemorrhagic disease with variable presentation. The clinical picture can be very severe, with the early occurrence of intracerebral hemorrhages or repeated hemarthroses, or, in contrast, moderate with cutaneous-mucosal hemorrhages (epistaxis, menorrhagia) or hemorrhages provoked by a surgical intervention. Finally, numerous subjects are completely asymptomatic despite very low factor VII levels. {ECO:0000269|PubMed:10862079, ECO:0000269|PubMed:11091194, ECO:0000269|PubMed:11129332, ECO:0000269|PubMed:12472587, ECO:0000269|PubMed:14717781, ECO:0000269|PubMed:1634227, ECO:0000269|PubMed:18976247, ECO:0000269|PubMed:19432927, ECO:0000269|PubMed:19751712, ECO:0000269|PubMed:2070047, ECO:0000269|PubMed:21206266, ECO:0000269|PubMed:21372693, ECO:0000269|PubMed:26761581, ECO:0000269|PubMed:7974346, ECO:0000269|PubMed:7981691, ECO:0000269|PubMed:8043443, ECO:0000269|PubMed:8204879, ECO:0000269|PubMed:8242057, ECO:0000269|PubMed:8364544, ECO:0000269|PubMed:8652821, ECO:0000269|PubMed:8844208, ECO:0000269|PubMed:8883260, ECO:0000269|PubMed:8940045, ECO:0000269|PubMed:9414278, ECO:0000269|PubMed:9452082, ECO:0000269|PubMed:9576180}. 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;Selenium Micronutrient Network;Vitamin B12 Metabolism;Folate Metabolism;Blood Clotting Cascade;BMAL1-CLOCK,NPAS2 activates circadian gene expression;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Complement and Coagulation Cascades;Circadian Clock;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;BMAL1:CLOCK,NPAS2 activates circadian gene expression;Extrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade);extrinsic prothrombin activation pathway (Consensus)

Recessive Scores

• pRec: 0.268

Intolerance Scores

• loftool: 0.0655
• rvis_EVS: -0.02
• rvis_percentile_EVS: 52.25

Haploinsufficiency Scores

• pHI: 0.103
• hipred: N
• hipred_score: 0.207
• ghis: 0.443

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.782

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: F7
• Phenotype: homeostasis/metabolism phenotype; craniofacial phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); growth/size/body region phenotype; skeleton phenotype; 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); 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); normal phenotype

Zebrafish Information Network

• Gene name: f7
• Affected structure: blood coagulation, fibrin clot formation
• Phenotype tag: abnormal
• Phenotype quality: delayed

Gene ontology

• Biological process: response to hypoxia;positive regulation of leukocyte chemotaxis;endoplasmic reticulum to Golgi vesicle-mediated transport;blood coagulation;blood coagulation, extrinsic pathway;circadian rhythm;response to carbon dioxide;positive regulation of platelet-derived growth factor receptor signaling pathway;protein processing;positive regulation of blood coagulation;positive regulation of cell migration;animal organ regeneration;response to estradiol;response to vitamin K;response to genistein;response to estrogen;positive regulation of positive chemotaxis;positive regulation of protein kinase B signaling;response to growth hormone;response to cholesterol;response to thyroxine;response to Thyroid stimulating hormone;response to 2,3,7,8-tetrachlorodibenzodioxine;response to astaxanthin;response to thyrotropin-releasing hormone
• Cellular component: extracellular region;extracellular space;endoplasmic reticulum lumen;Golgi lumen;plasma membrane;vesicle;serine-type peptidase complex
• Molecular function: serine-type endopeptidase activity;signaling receptor binding;calcium ion binding;protein binding;serine-type peptidase activity