FGG

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

Basic information

Region (hg38): 4:154604133-154612967

Links

ENSG00000171557 ∙ NCBI:2266 ∙ OMIM:134850 ∙ HGNC:3694 ∙ Uniprot:P02679 ∙ 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
• familial dysfibrinogenemia (Strong), 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	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	4956920; 4427684; 6886002; 4002201; 3563970; 3708159; 3742050; 3337908; 2617471; 2496144; 2257302; 2328317; 7635941; 9746756; 2971042; 2971046; 2738036; 2819242; 2071611; 1471077; 1733971; 8470043; 7740487; 8822581; 9368024; 11001902; 11071644; 11001903; 11435303; 11986213; 17854317; 18832913; 19551918; 20135062; 20580695; 20589319; 20978265

ClinVar

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

• not provided (53 variants)
• Congenital afibrinogenemia (34 variants)
• Inborn genetic diseases (11 variants)
• Familial dysfibrinogenemia (10 variants)
• not specified (9 variants)
• Hypofibrinogenemia (9 variants)
• Abnormal bleeding (3 variants)
• FGG-related condition (2 variants)
• Afibrinogenemia (2 variants)
• Thromboembolism (2 variants)
• Thrombocytopenia;Abnormal bleeding (1 variants)
• FIBRINOGEN TOKYO 2 (1 variants)
• Hereditary spastic paraplegia 4 (1 variants)
• Hypodysfibrinogenemia (1 variants)
• Thrombus (1 variants)
• Fibrinogen Milano XII, digenic (1 variants)
• FIBRINOGEN HAIFA 1 (1 variants)
• FIBRINOGEN ASAHI (1 variants)
• Hemorrhage (1 variants)
• Dysfibrinogenemia (1 variants)
• FIBRINOGEN BALTIMORE 3 (1 variants)
• FIBRINOGEN PARIS 1 (1 variants)
• Congenital fibrinogen deficiency (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FGG 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			3	3	1	7
missense	4	7	46	3	1	61
nonsense	2					2
start loss						0
frameshift	1	2				3
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region		1			1	2
non coding			6	7	7	20
Total	7	9	55	13	9

Highest pathogenic variant AF is 0.00000657

Variants in FGG

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

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

Position	Type	Phenotype	Significance	ClinVar
4-154604299-T-C		Congenital afibrinogenemia	Likely benign (Jan 13, 2018)
4-154604334-G-A		Congenital afibrinogenemia • not specified	Uncertain significance (Dec 12, 2023)
4-154604338-T-G		Congenital afibrinogenemia • FGG-related disorder	Conflicting classifications of pathogenicity (Mar 02, 2020)
4-154604340-T-C		Congenital afibrinogenemia	Uncertain significance (Jan 12, 2018)
4-154604346-G-A		Congenital afibrinogenemia	Conflicting classifications of pathogenicity (Jun 27, 2022)
4-154604354-C-A			Uncertain significance (Jul 18, 2022)
4-154604393-A-T			Benign (May 12, 2021)
4-154604543-G-A			Benign (Nov 11, 2018)
4-154604877-G-A			Likely benign (May 01, 2022)
4-154604896-C-A		Congenital afibrinogenemia	Uncertain significance (-)
4-154604906-T-TC			Likely pathogenic (Sep 15, 2018)
4-154604911-C-A		Congenital afibrinogenemia	Uncertain significance (Oct 19, 2023)
4-154604923-G-T			Uncertain significance (Feb 27, 2023)
4-154604938-T-C		Congenital afibrinogenemia	Uncertain significance (Mar 02, 2018)
4-154604959-T-C		Congenital afibrinogenemia	Uncertain significance (Jan 12, 2018)
4-154604986-A-G		Hypodysfibrinogenemia	Uncertain significance (Jul 29, 2020)
4-154604994-C-T		Congenital afibrinogenemia	Uncertain significance (Apr 28, 2021)
4-154604995-G-A		Hereditary spastic paraplegia 4	Pathogenic (Dec 05, 2022)
4-154604995-G-C		FIBRINOGEN OSAKA 5	other (Sep 26, 2014)
4-154604997-G-C		Inborn genetic diseases	Likely benign (Aug 12, 2022)
4-154605006-G-A		Afibrinogenemia • Dysfibrinogenemia	Uncertain significance (Dec 08, 2021)
4-154605024-T-A			Likely pathogenic (Oct 17, 2022)
4-154605028-C-G		FIBRINOGEN MATSUMOTO 1	other (Sep 26, 2014)
4-154605049-C-G		Inborn genetic diseases	Uncertain significance (Jul 19, 2022)
4-154605058-A-T			Uncertain significance (Mar 03, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FGG	protein_coding	protein_coding	ENST00000336098	9	8834

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0496	0.950	125723	0	11	125734	0.0000437

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.20	184	236	0.780	0.0000114	3002
Missense in Polyphen		70	111.45	0.62809		1436
Synonymous	-0.138	88	86.4	1.02	0.00000450	796
Loss of Function	3.28	7	24.5	0.285	0.00000121	297

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000622	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.000220	0.000217
Finnish	0.00	0.00
European (Non-Finnish)	0.0000176	0.0000176
Middle Eastern	0.000220	0.000217
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Together with fibrinogen alpha (FGA) and fibrinogen beta (FGB), polymerizes to form an insoluble fibrin matrix. 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 via an ITGB3- dependent pathway. 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: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:15632207, ECO:0000269|PubMed:2257302, ECO:0000269|PubMed:2976995, ECO:0000269|PubMed:3708159}. 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);Staphylococcus aureus infection - 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 Blood Clotting Cascade;MAP2K and MAPK activation;Disease;Signal Transduction;fibrinolysis pathway;intrinsic prothrombin activation pathway;Post-translational protein phosphorylation;Integrin cell surface interactions;Toll-Like Receptors Cascades;Post-translational protein modification;Metabolism of proteins;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;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet Aggregation (Plug Formation);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Beta3 integrin cell surface interactions;Integrin signaling;Glucocorticoid receptor regulatory network;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;IL6-mediated signaling events;Beta2 integrin cell surface interactions;extrinsic prothrombin activation pathway (Consensus)

Recessive Scores

• pRec: 0.352

Intolerance Scores

• loftool: 0.126
• rvis_EVS: -0.03
• rvis_percentile_EVS: 51.92

Haploinsufficiency Scores

• pHI: 0.419
• hipred: Y
• hipred_score: 0.519
• ghis: 0.566

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.917

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Fgg
• Phenotype: growth/size/body region phenotype; homeostasis/metabolism phenotype; hematopoietic system 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); reproductive system phenotype; embryo phenotype; immune system phenotype

Gene ontology

• Biological process: toll-like receptor signaling pathway;platelet degranulation;cell-matrix adhesion;blood coagulation;protein secretion;extracellular matrix organization;plasminogen activation;positive regulation of heterotypic cell-cell adhesion;cellular protein-containing complex assembly;platelet maturation;fibrinolysis;post-translational protein modification;cellular protein metabolic process;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;cellular response to interleukin-6;blood coagulation, fibrin clot formation;positive regulation of peptide hormone secretion;negative regulation of platelet aggregation;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 lumen;plasma membrane;external side of plasma membrane;cell surface;platelet alpha granule;platelet alpha granule lumen;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
• Molecular function: signaling receptor binding;structural molecule activity;extracellular matrix structural constituent;protein binding;protein homodimerization activity;metal ion binding;cell adhesion molecule binding