FGB

fibrinogen beta chain, the group of Receptor ligands|Fibrinogen C domain containing

Basic information

Region (hg38): 4:154563011-154572807

Links

ENSG00000171564 ∙ NCBI:2244 ∙ OMIM:134830 ∙ HGNC:3662 ∙ Uniprot:P02675 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• thrombophilia (Strong), mode of inheritance: AD
• thrombophilia (Strong), mode of inheritance: AR
• congenital afibrinogenemia (Supportive), mode of inheritance: AR
• familial dysfibrinogenemia (Supportive), mode of inheritance: AD
• familial hypofibrinogenemia (Supportive), mode of inheritance: AD
• congenital afibrinogenemia (Strong), mode of inheritance: AR
• congenital fibrinogen deficiency (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Afibrinogenemia, congenital; Dysfibrinogenemia, congenital; Hypodysfibrinogenemia, congenital	AD/AR	Hematologic	Individuals with afibrinogenemia/dysfibrinogenemia are at risk of a variety of bleeding diatheses; Preventive or treatment-based (eg, with fibrinogen in the case of congenital afibrinogenemia) may be beneficial	Hematologic	3156856; 2885451; 3388290; 2018836; 1565641; 1634610; 9185528; 10666208; 11468164; 11425767; 12393540; 15070683; 18853456; 21301788; 22955321

ClinVar

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

• not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGB 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			2	12	6	20
missense		2	78	3	1	84
nonsense		1	1			2
start loss						0
frameshift	1	1	1			3
inframe indel		1				1
splice donor/acceptor (+/-2bp)						0
splice region			2			2
non coding		1	37	6	31	75
Total	1	6	119	21	38

Variants in FGB

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

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

Position	Type	Phenotype	Significance	ClinVar
4-154563012-AGT-A		Congenital afibrinogenemia	Uncertain significance (Jun 14, 2016)
4-154563013-G-A		not specified	Uncertain significance (Oct 30, 2024)
4-154563022-A-G		Congenital afibrinogenemia • Inborn genetic diseases	Uncertain significance (Aug 20, 2024)
4-154563028-A-T			Uncertain significance (Oct 28, 2022)
4-154563034-T-C		Inborn genetic diseases	Uncertain significance (Jul 25, 2023)
4-154563052-C-G		not specified	Uncertain significance (Nov 18, 2024)
4-154563085-T-C			Likely benign (Sep 08, 2023)
4-154563098-T-C		Congenital afibrinogenemia	Uncertain significance (Jan 12, 2018)
4-154563102-T-A			Likely benign (Jul 12, 2023)
4-154563110-A-G		Inborn genetic diseases	Uncertain significance (May 11, 2022)
4-154563115-G-A		Inborn genetic diseases	Uncertain significance (Oct 04, 2024)
4-154563118-A-G		Inborn genetic diseases	Likely benign (Oct 26, 2021)
4-154563121-G-A		Congenital afibrinogenemia • Inborn genetic diseases	Uncertain significance (Mar 31, 2023)
4-154563132-G-C		FGB-related disorder	Uncertain significance (Sep 30, 2023)
4-154563137-AT-A		Congenital afibrinogenemia • not specified	Uncertain significance (Feb 25, 2022)
4-154563359-G-A			Benign (Nov 12, 2018)
4-154565229-C-T			Benign (Nov 12, 2018)
4-154565318-T-A			Benign (Nov 12, 2018)
4-154565494-T-C			Benign (Nov 12, 2018)
4-154565791-T-C			Likely benign (Oct 22, 2023)
4-154565796-C-T		Congenital afibrinogenemia • not specified	Conflicting classifications of pathogenicity (Dec 11, 2023)
4-154565818-G-C			Uncertain significance (Oct 28, 2024)
4-154565823-C-T		FIBRINOGEN CHRISTCHURCH 2 • See cases • Hypofibrinogenemia	Likely pathogenic (Dec 19, 2023)
4-154565825-TG-T			Pathogenic (Aug 26, 2022)
4-154565826-G-T		FIBRINOGEN ISE	other (Sep 29, 2014)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGB	protein_coding	protein_coding	ENST00000302068	8	8131

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.566	0.434	125733	0	15	125748	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.732	231	264	0.873	0.0000136	3254
Missense in Polyphen		66	104.81	0.62969		1174
Synonymous	-0.719	99	90.3	1.10	0.00000483	862
Loss of Function	3.63	5	24.3	0.206	0.00000110	304

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000616	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000109	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.0000885	0.0000879
Middle Eastern	0.000109	0.000109
South Asian	0.0000653	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Cleaved by the protease thrombin to yield monomers which, together with fibrinogen alpha (FGA) and fibrinogen gamma (FGG), polymerize to form an insoluble fibrin matrix. Fibrin has a major function in hemostasis as one of the primary components of blood clots. In addition, functions during the early stages of wound repair to stabilize the lesion and guide cell migration during re-epithelialization. Was originally thought to be essential for platelet aggregation, based on in vitro studies using anticoagulated blood. However subsequent studies have shown that it is not absolutely required for thrombus formation in vivo. Enhances expression of SELP in activated platelets. Maternal fibrinogen is essential for successful pregnancy. Fibrin deposition is also associated with infection, where it protects against IFNG-mediated hemorrhage. May also facilitate the antibacterial immune response via both innate and T-cell mediated pathways. {ECO:0000250|UniProtKB:E9PV24}.
• Disease: DISEASE: Congenital afibrinogenemia (CAFBN) [MIM:202400]: Rare autosomal recessive disorder is characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. {ECO:0000269|PubMed:10666208, ECO:0000269|PubMed:11468164, ECO:0000269|PubMed:15070683, ECO:0000269|PubMed:25427968}. Note=The disease is caused by mutations affecting the gene represented in this entry. Patients with congenital fibrinogen abnormalities can manifest different clinical pictures. Some cases are clinically silent, some show a tendency toward bleeding and some show a predisposition for thrombosis with or without bleeding.; DISEASE: Dysfibrinogenemia, congenital (DYSFIBRIN) [MIM:616004]: A disorder characterized by qualitative abnormalities (dysfibrinogenemia) of the circulating fibrinogen. Affected individuals are frequently asymptomatic, but some patients have bleeding diathesis, thromboembolic complications, or both. In some cases, dysfibrinogenemia is associated with low circulating fibrinogen levels (hypodysfibrinogenemia). {ECO:0000269|PubMed:1634610}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Complement and coagulation cascades - Homo sapiens (human);Platelet activation - Homo sapiens (human);Platelet Aggregation Inhibitor 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;Human Complement System;VEGFA-VEGFR2 Signaling Pathway;Dengue-2 Interactions with Complement and Coagulation Cascades;Dengue-2 Interactions with Blood Clotting Cascade;Complement and Coagulation Cascades;MAP2K and MAPK activation;Disease;Signal Transduction;fibrinolysis pathway;intrinsic prothrombin activation pathway;Integrin cell surface interactions;Toll-Like Receptors Cascades;Extracellular matrix organization;GRB2:SOS provides linkage to MAPK signaling for Integrins ;p130Cas linkage to MAPK signaling for integrins;Integrin alphaIIb beta3 signaling;Innate Immune System;Immune System;Platelet Aggregation (Plug Formation);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Beta3 integrin cell surface interactions;Integrin signaling;Hemostasis;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;Common Pathway of Fibrin Clot Formation;Formation of Fibrin Clot (Clotting Cascade);Regulation of TLR by endogenous ligand;Signaling by RAS mutants;Signaling by high-kinase activity BRAF mutants;Signaling by moderate kinase activity BRAF mutants;Paradoxical activation of RAF signaling by kinase inactive BRAF;Signaling by BRAF and RAF fusions;Oncogenic MAPK signaling;Diseases of signal transduction;Beta1 integrin cell surface interactions;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Beta2 integrin cell surface interactions;extrinsic prothrombin activation pathway (Consensus)

Recessive Scores

• pRec: 0.411

Intolerance Scores

• loftool: 0.194
• rvis_EVS: 0.31
• rvis_percentile_EVS: 72.6

Haploinsufficiency Scores

• pHI: 0.729
• hipred: Y
• hipred_score: 0.755
• ghis: 0.638

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.781

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgb
• Phenotype: endocrine/exocrine gland 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); reproductive system phenotype

Gene ontology

• Biological process: toll-like receptor signaling pathway;adaptive immune response;platelet degranulation;cell-matrix adhesion;blood coagulation;extracellular matrix organization;plasminogen activation;positive regulation of heterotypic cell-cell adhesion;cellular protein-containing complex assembly;fibrinolysis;induction of bacterial agglutination;cellular response to leptin stimulus;innate immune response;positive regulation of vasoconstriction;positive regulation of exocytosis;positive regulation of protein secretion;protein polymerization;response to calcium ion;positive regulation of ERK1 and ERK2 cascade;platelet aggregation;cellular response to interleukin-1;blood coagulation, fibrin clot formation;positive regulation of peptide hormone secretion;positive regulation of substrate adhesion-dependent cell spreading;negative regulation of extrinsic apoptotic signaling pathway via death domain receptors;negative regulation of endothelial cell apoptotic process
• Cellular component: extracellular region;fibrinogen complex;extracellular space;endoplasmic reticulum;plasma membrane;cell cortex;external side of plasma membrane;cell surface;platelet alpha granule;platelet alpha granule lumen;synapse;collagen-containing extracellular matrix;extracellular exosome;blood microparticle;extracellular vesicle
• Molecular function: signaling receptor binding;structural molecule activity;extracellular matrix structural constituent;protein binding;cell adhesion molecule binding;chaperone binding