CAFBN
MCID: AFB002
MIFTS: 54

Afibrinogenemia, Congenital (CAFBN) malady

Categories: Genetic diseases, Blood diseases, Rare diseases

Aliases & Classifications for Afibrinogenemia, Congenital

Aliases & Descriptions for Afibrinogenemia, Congenital:

Name: Afibrinogenemia, Congenital 54 13
Congenital Afibrinogenemia 12 25 66 52 14
Afibrinogenemia 25 42 69
Familial Afibrinogenemia 25 56
Afibrinogenemia, Congenital Hypofibrinogenemia, Congenital, Included 54
Complement Factor I Deficiency 69
Hypofibrinogenemia, Congenital 54
Congenital Hypofibrinogenemia 69
Familial Hypofibrinogenemia 56
Afibrinogenemia Congenital 29
Fibrinogen Deficiency 12
Factor I Deficiency 12
Hypofibrinogenemia 69
Cafbn 66

Characteristics:

Orphanet epidemiological data:

56
familial afibrinogenemia
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;
familial hypofibrinogenemia
Inheritance: Autosomal dominant; Age of onset: All ages;

HPO:

32
afibrinogenemia, congenital:
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 54 202400
Disease Ontology 12 DOID:2236
ICD10 33 D68.2
MeSH 42 D000347
ICD10 via Orphanet 34 D68.2
UMLS 69 C0001733

Summaries for Afibrinogenemia, Congenital

OMIM : 54 Inherited disorders of fibrinogen affect either the quantity (afibrinogenemia and hypofibrinogenemia; 202400) or the... (202400) more...

MalaCards based summary : Afibrinogenemia, Congenital, also known as congenital afibrinogenemia, is related to lupus erythematosus and complement factor i deficiency, and has symptoms including joint swelling, menometrorrhagia and abnormal bleeding. An important gene associated with Afibrinogenemia, Congenital is FGA (Fibrinogen Alpha Chain), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Development Angiotensin activation of ERK. The drug Complement Factor I has been mentioned in the context of this disorder. Affiliated tissues include skin, liver and tongue, and related phenotypes are cardiovascular system and hematopoietic system

Genetics Home Reference : 25 Congenital afibrinogenemia is a bleeding disorder caused by impairment of the blood clotting process. Normally, blood clots protect the body after an injury by sealing off damaged blood vessels and preventing further blood loss. However, bleeding is uncontrolled in people with congenital afibrinogenemia. Newborns with this condition often experience prolonged bleeding from the umbilical cord stump after birth. Nosebleeds (epistaxis) and bleeding from the gums or tongue are common and can occur after minor trauma or in the absence of injury (spontaneous bleeding). Some affected individuals experience bleeding into the spaces between joints (hemarthrosis) or the muscles (hematoma). Rarely, bleeding in the brain or other internal organs occurs, which can be fatal. Women with congenital afibrinogenemia can have abnormally heavy menstrual bleeding (menorrhagia). Without proper treatment, women with this disorder may have difficulty carrying a pregnancy to term, resulting in repeated miscarriages.

UniProtKB/Swiss-Prot : 66 Congenital afibrinogenemia: 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.

Related Diseases for Afibrinogenemia, Congenital

Diseases in the Afibrinogenemia family:

Afibrinogenemia, Congenital Fga-Related Congenital Afibrinogenemia
Fgb-Related Congenital Afibrinogenemia Fgg-Related Congenital Afibrinogenemia

Diseases related to Afibrinogenemia, Congenital via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 141)
id Related Disease Score Top Affiliating Genes
1 lupus erythematosus 28.9 F3 PLAT SERPINC1 VWF
2 complement factor i deficiency 12.4
3 fibrinogen deficiency, congenital 12.0
4 fga-related congenital afibrinogenemia 11.8
5 fgb-related congenital afibrinogenemia 11.8
6 fgg-related congenital afibrinogenemia 11.8
7 growth retardation with deafness and mental retardation due to igf1 deficiency 11.5
8 insulin-like growth factor i 11.5
9 afibrinogenemia 11.4
10 complement factor h deficiency 10.8
11 hemarthrosis 10.3 F2 F3
12 hendra virus infection 10.2 F2 F3
13 dyskinetic cerebral palsy 10.2 F2 F3
14 stroke, ischemic 10.2 F2 F3
15 vascular erectile tumor 10.2 F2 SERPINC1
16 mixed epithelial tumor of ovary 10.2 F2 SERPINC1
17 may-hegglin anomaly 10.2 F2 SERPINC1
18 sporotrichosis 10.2 F2 F3
19 sertoli cell tumor 10.2 F3 SERPINC1
20 hereditary endotheliopathy, retinopathy, nephropathy, and stroke 10.2 F3 SERPINC1
21 chronic inflammatory demyelinating polyneuritis 10.2 F2 F3
22 seminoma 10.2 F2 F3
23 left-right axis malformations 10.2 F2 SERPINC1
24 lymphocytic colitis 10.2 F2 SERPINC1
25 small intestinal l-cell glucagon-like peptide producing tumor 10.2 F2 VWF
26 brain stem cancer 10.2 F2 F3
27 schwannoma of jugular foramen 10.2 F2 SERPINC1
28 bullous skin disease 10.2 F2 SERPINC1
29 citrulline transport defect 10.2 F2 FGA FGB
30 neuronopathy, distal hereditary motor, type iid 10.2 F3 SERPINC1
31 neuroaxonal dystrophy 10.2 F2 SERPINC1
32 cerebellar astrocytoma 10.2 F2 SERPINC1
33 periosteal chondrosarcoma 10.2 F2 SERPINC1
34 hodgkin's lymphoma, lymphocytic depletion 10.2 C3 F2
35 unverricht-lundborg syndrome 10.2 FGB PLAT
36 coloboma of optic papilla 10.2 SERPINC1 SERPINF2
37 angelucci's syndrome 10.1 F2 SERPINC1
38 brazilian hemorrhagic fever 10.1 PLAT SERPINC1
39 freiberg's disease 10.1 F2 F3 SERPINC1
40 immunodeficiency 21 10.1 F2 FGA VWF
41 pancreatic ductal carcinoma 10.1 F2 F3 SERPINC1
42 chorioretinal scar 10.1 F2 F3 SERPINC1
43 melorheostosis 10.1 PLAT SERPINC1
44 spinal cord lipoma 10.1 F2 F3 SERPINC1
45 midline cystocele 10.1 F2 F3 SERPINC1
46 blepharoconjunctivitis 10.1 F2 F3 SERPINC1
47 intestinal disaccharidase deficiency 10.1 F2 F3 SERPINC1
48 hereditary alpha tryptasemia syndrome 10.1 F2 F3 SERPINC1
49 fanconi-bickel syndrome 10.1 PLAT SERPINC1
50 scapuloperoneal myopathy, x-linked dominant 10.1 F2 F3 SERPINC1

Graphical network of the top 20 diseases related to Afibrinogenemia, Congenital:



Diseases related to Afibrinogenemia, Congenital

Symptoms & Phenotypes for Afibrinogenemia, Congenital

Symptoms by clinical synopsis from OMIM:

202400

Clinical features from OMIM:

202400

Human phenotypes related to Afibrinogenemia, Congenital:

56 32 (show all 10)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 joint swelling 56 32 Very frequent (99-80%) HP:0001386
2 menometrorrhagia 56 32 Very frequent (99-80%) HP:0400008
3 abnormal bleeding 56 32 Very frequent (99-80%),Very frequent (99-80%) HP:0001892
4 gastrointestinal hemorrhage 56 32 Very frequent (99-80%) HP:0002239
5 epistaxis 56 32 Very frequent (99-80%),Very frequent (99-80%) HP:0000421
6 gingival bleeding 56 32 Very frequent (99-80%),Very frequent (99-80%) HP:0000225
7 cerebral hemorrhage 56 32 Occasional (29-5%) HP:0001342
8 spontaneous abortion 56 32 Very frequent (99-80%) HP:0005268
9 hypofibrinogenemia 32 HP:0011900
10 splenic rupture 32 HP:0012223

MGI Mouse Phenotypes related to Afibrinogenemia, Congenital:

44
id Description MGI Source Accession Score Top Affiliating Genes
1 cardiovascular system MP:0005385 10.02 C3 F2 F3 FGA FGB FGG
2 hematopoietic system MP:0005397 9.91 FGG PLAT SERPINC1 VWF C3 CFI
3 homeostasis/metabolism MP:0005376 9.85 C3 CFI F2 F3 FGA FGG
4 embryo MP:0005380 9.8 C3 F2 F3 FGA FGG SERPINC1
5 immune system MP:0005387 9.56 VWF C3 F2 F3 FGA FGG
6 reproductive system MP:0005389 9.17 C3 F2 FGA FGB FGG PLAT

Drugs & Therapeutics for Afibrinogenemia, Congenital

Drugs for Afibrinogenemia, Congenital (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):


id Name Status Phase Clinical Trials Cas Number PubChem Id
1 Complement Factor I

Interventional clinical trials:


id Name Status NCT ID Phase
1 Human Fibrinogen Concentrate in Pediatric Cardiac Surgery Recruiting NCT02822599 Phase 4
2 Human Fibrinogen Concentrate (FGTW) in Pediatric Patients With Congenital Fibrinogen Deficiency Completed NCT02094430 Phase 2, Phase 3
3 Pharmacokinetic, Efficacy and Safety of BT524 in Patients With Congenital Fibrinogen Deficiency Recruiting NCT02065882 Phase 2, Phase 3
4 Efficacy and Safety Study of Octafibrin for On-demand Treatment of Acute Bleeding and to Prevent Bleeding During and After Surgery Recruiting NCT02267226 Phase 3
5 Study to Assess the Efficacy, Safety and Pharmacokinetic of Octafibrin in Paediatric Subjects With Fibrinogen Deficiency Recruiting NCT02408484 Phase 3
6 Fibrinogen Concentrate (Human) − Efficacy and Safety Study Withdrawn NCT00916656 Phase 3
7 Pharmacokinetic, Efficacy, and Safety Study of Octafibrin Compared to Haemocomplettan/Riastap Completed NCT01575756 Phase 2
8 Human Fibrinogen - Pharmacokinetics Completed NCT00496262 Phase 2
9 Pharmacokinetics, Efficacy, and Safety of Human Plasma-Derived Fibrinogen (FIB Grifols) in Patients With Congenital Afibrinogenaemia Recruiting NCT02281500 Phase 1, Phase 2
10 An Observational Cohort Study of the Safety and Efficacy of Fibrinogen Concentrate, Human (FCH) in Subjects With Congenital Fibrinogen Deficiency Active, not recruiting NCT02427217

Search NIH Clinical Center for Afibrinogenemia, Congenital

Cochrane evidence based reviews: afibrinogenemia

Genetic Tests for Afibrinogenemia, Congenital

Genetic tests related to Afibrinogenemia, Congenital:

id Genetic test Affiliating Genes
1 Afibrinogenemia, Congenital 29

Anatomical Context for Afibrinogenemia, Congenital

MalaCards organs/tissues related to Afibrinogenemia, Congenital:

39
Skin, Liver, Tongue, Brain, Spleen

Publications for Afibrinogenemia, Congenital

Variations for Afibrinogenemia, Congenital

UniProtKB/Swiss-Prot genetic disease variations for Afibrinogenemia, Congenital:

66 (show all 13)
id Symbol AA change Variation ID SNP ID
1 FGA p.Cys55Arg VAR_072721
2 FGA p.Arg129Pro VAR_072722
3 FGA p.Cys184Trp VAR_072723
4 FGB p.Arg196Cys VAR_016908 rs121909623
5 FGB p.Leu383Arg VAR_016909 rs121909621
6 FGB p.Gly430Asp VAR_016910 rs121909622
7 FGB p.Leu202Gln VAR_072620 rs121909624
8 FGB p.Cys95Arg VAR_072724
9 FGB p.Thr407Lys VAR_072725
10 FGG p.Thr303Pro VAR_072726
11 FGG p.Asp327His VAR_072727
12 FGG p.Asn345Asp VAR_072728
13 FGG p.Arg401Trp VAR_072729 rs75848804

ClinVar genetic disease variations for Afibrinogenemia, Congenital:

6 (show all 19)
id Gene Variation Type Significance SNP ID Assembly Location
1 CFI NM_000204.4(CFI): c.1253A> T (p.His418Leu) single nucleotide variant Pathogenic rs121964912 GRCh37 Chromosome 4, 110667554: 110667554
2 CFI CFI, IVS5DS G-A, -1 single nucleotide variant Pathogenic
3 CFI CFI, 2-BP INS, 1205AT insertion Pathogenic
4 CFI NM_000204.4(CFI): c.728G> A (p.Gly243Asp) single nucleotide variant Pathogenic rs121964916 GRCh37 Chromosome 4, 110681723: 110681723
5 FGG NM_021870.2(FGG): c.78+5G> A single nucleotide variant Pathogenic rs587776837 GRCh38 Chromosome 4, 154612527: 154612527
6 FGG NM_021870.2(FGG): c.307+5G> A single nucleotide variant Pathogenic rs587776838 GRCh37 Chromosome 4, 155533165: 155533165
7 FGG NM_021870.2(FGG): c.667-320A> T single nucleotide variant Pathogenic rs587776839 GRCh38 Chromosome 4, 154608970: 154608970
8 FGB NM_005141.4(FGB): c.1148T> G (p.Leu383Arg) single nucleotide variant Pathogenic rs121909621 GRCh37 Chromosome 4, 155490855: 155490855
9 FGB NM_005141.4(FGB): c.1289G> A (p.Gly430Asp) single nucleotide variant Pathogenic rs121909622 GRCh37 Chromosome 4, 155491615: 155491615
10 FGB NM_005141.4(FGB): c.958+13C> T single nucleotide variant Pathogenic rs606231223 GRCh38 Chromosome 4, 154569320: 154569320
11 FGB NM_005141.4(FGB): c.1244+1G> T single nucleotide variant Pathogenic rs606231224 GRCh38 Chromosome 4, 154569800: 154569800
12 FGB NM_005141.4(FGB): c.605T> A (p.Leu202Gln) single nucleotide variant Pathogenic rs121909624 GRCh37 Chromosome 4, 155488859: 155488859
13 FGB NM_005141.4(FGB): c.139C> T (p.Arg47Ter) single nucleotide variant Pathogenic rs121909625 GRCh37 Chromosome 4, 155486984: 155486984
14 FGA NC_000004.12 deletion Pathogenic GRCh38 Chromosome 4, 154580323: 154590216
15 FGA NM_000508.4(FGA): c.510+1G> T single nucleotide variant Pathogenic rs146387238 GRCh37 Chromosome 4, 155508663: 155508663
16 FGA NM_000508.4(FGA): c.711dupT (p.Lys238Terfs) duplication Pathogenic rs606231225 GRCh38 Chromosome 4, 154586718: 154586718
17 FGA NM_000508.4(FGA): c.991A> G (p.Thr331Ala) single nucleotide variant risk factor rs6050 GRCh37 Chromosome 4, 155507590: 155507590
18 CFI NM_000204.4(CFI): c.80_81delAT (p.Asp27Alafs) deletion Pathogenic rs886043418 GRCh37 Chromosome 4, 110687957: 110687958
19 FGA NM_000508.4(FGA): c.502C> T (p.Arg168Ter) single nucleotide variant Pathogenic rs755117226 GRCh37 Chromosome 4, 155508672: 155508672

Expression for Afibrinogenemia, Congenital

Search GEO for disease gene expression data for Afibrinogenemia, Congenital.

Pathways for Afibrinogenemia, Congenital

Pathways related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

(show all 14)
id Super pathways Score Top Affiliating Genes
1
Show member pathways
12.99 F2 F3 FGA FGB FGG PLAT
2
Show member pathways
12.6 F2 FGA FGB FGG
3
Show member pathways
12.6 F2 F3 FGA FGB FGG SERPINC1
4
Show member pathways
12.1 FGA FGB FGG VWF
5
Show member pathways
11.95 FGA FGB FGG VWF
6
Show member pathways
11.89 FGA FGB FGG VWF
7 11.84 C3 CFI F2 F3 FGA FGB
8 11.82 FGA FGB FGG VWF
9
Show member pathways
11.71 F2 FGA FGB FGG VWF
10
Show member pathways
11.48 F2 F3 FGA FGB FGG PLAT
11 11.43 C3 CFI FGG
12 11.36 FGA FGB FGG PLAT
13 11.26 F2 FGA FGB FGG VWF
14 10.64 PLAT SERPINF2

GO Terms for Afibrinogenemia, Congenital

Cellular components related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

(show all 11)
id Name GO ID Score Top Affiliating Genes
1 cell surface GO:0009986 9.91 F3 FGA FGB FGG PLAT SERPINF2
2 endoplasmic reticulum lumen GO:0005788 9.85 C3 F2 FGA FGG SERPINC1
3 extracellular space GO:0005615 9.85 C3 CFI F2 F3 FGA FGB
4 platelet alpha granule lumen GO:0031093 9.8 FGA FGB FGG SERPINF2 VWF
5 external side of plasma membrane GO:0009897 9.78 F2 FGA FGB FGG
6 cell cortex GO:0005938 9.67 FGA FGB FGG
7 platelet alpha granule GO:0031091 9.62 FGA FGB FGG VWF
8 fibrinogen complex GO:0005577 9.26 FGA FGB FGG SERPINF2
9 blood microparticle GO:0072562 9.17 C3 F2 FGA FGB FGG SERPINC1
10 extracellular exosome GO:0070062 10.11 C3 CFI F2 F3 FGA FGB
11 extracellular region GO:0005576 10 C3 CFI F2 F3 FGA FGB

Biological processes related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

(show all 35)
id Name GO ID Score Top Affiliating Genes
1 innate immune response GO:0045087 9.96 C3 CFI FGA FGB
2 post-translational protein modification GO:0043687 9.94 C3 FGA FGG SERPINC1
3 extracellular matrix organization GO:0030198 9.91 FGA FGB FGG VWF
4 positive regulation of ERK1 and ERK2 cascade GO:0070374 9.9 FGA FGB FGG SERPINF2
5 cellular protein metabolic process GO:0044267 9.89 C3 F2 FGA FGG SERPINC1
6 negative regulation of endopeptidase activity GO:0010951 9.82 C3 SERPINC1 SERPINF2
7 regulation of complement activation GO:0030449 9.81 C3 CFI F2
8 cell-matrix adhesion GO:0007160 9.8 FGA FGB FGG
9 platelet degranulation GO:0002576 9.8 FGA FGB FGG SERPINF2 VWF
10 response to calcium ion GO:0051592 9.79 FGA FGB FGG
11 toll-like receptor signaling pathway GO:0002224 9.77 FGA FGB FGG
12 platelet aggregation GO:0070527 9.76 FGA FGB FGG
13 blood coagulation GO:0007596 9.76 F2 F3 FGA FGB FGG PLAT
14 positive regulation of protein secretion GO:0050714 9.75 FGA FGB FGG
15 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors GO:1902042 9.74 FGA FGB FGG
16 positive regulation of vasoconstriction GO:0045907 9.73 FGA FGB FGG
17 positive regulation of substrate adhesion-dependent cell spreading GO:1900026 9.72 FGA FGB FGG
18 platelet activation GO:0030168 9.72 F2 FGA FGB FGG VWF
19 negative regulation of endothelial cell apoptotic process GO:2000352 9.71 FGA FGB FGG
20 positive regulation of exocytosis GO:0045921 9.7 FGA FGB FGG
21 cellular protein complex assembly GO:0043623 9.69 FGA FGB FGG
22 acute-phase response GO:0006953 9.67 F2 SERPINF2
23 positive regulation of collagen biosynthetic process GO:0032967 9.66 F2 SERPINF2
24 negative regulation of proteolysis GO:0045861 9.65 F2 PLAT
25 regulation of blood coagulation GO:0030193 9.65 F2 SERPINC1
26 protein polymerization GO:0051258 9.65 FGA FGB FGG
27 blood coagulation, intrinsic pathway GO:0007597 9.64 F2 VWF
28 positive regulation of heterotypic cell-cell adhesion GO:0034116 9.63 FGA FGB FGG
29 negative regulation of fibrinolysis GO:0051918 9.62 F2 SERPINF2
30 induction of bacterial agglutination GO:0043152 9.61 FGA FGB
31 positive regulation of peptide hormone secretion GO:0090277 9.61 FGA FGB FGG
32 plasminogen activation GO:0031639 9.56 FGA FGB FGG PLAT
33 blood coagulation, fibrin clot formation GO:0072378 9.54 FGA FGB FGG
34 fibrinolysis GO:0042730 9.43 F2 FGA FGB FGG PLAT SERPINF2
35 hemostasis GO:0007599 9.17 F2 F3 FGA FGB FGG SERPINC1

Molecular functions related to Afibrinogenemia, Congenital according to GeneCards Suite gene sharing:

id Name GO ID Score Top Affiliating Genes
1 structural molecule activity GO:0005198 9.63 FGA FGB FGG
2 serine-type peptidase activity GO:0008236 9.58 CFI F2 PLAT
3 protein binding, bridging GO:0030674 9.5 FGA FGB FGG
4 protease binding GO:0002020 9.46 F3 SERPINC1 SERPINF2 VWF
5 endopeptidase inhibitor activity GO:0004866 9.43 C3 SERPINF2
6 cell adhesion molecule binding GO:0050839 9.43 FGA FGB FGG
7 serine-type endopeptidase activity GO:0004252 9.35 C3 CFI F2 F3 PLAT
8 receptor binding GO:0005102 9.1 C3 F2 FGA FGB FGG PLAT
9 protein binding GO:0005515 10.11 C3 CFI F2 F3 FGA FGB

Sources for Afibrinogenemia, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 PubMed
60 QIAGEN
65 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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