F5F8D2
MCID: FCT034
MIFTS: 38

Factor V and Factor Viii, Combined Deficiency of, 2 (F5F8D2)

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for Factor V and Factor Viii, Combined Deficiency of, 2

MalaCards integrated aliases for Factor V and Factor Viii, Combined Deficiency of, 2:

Name: Factor V and Factor Viii, Combined Deficiency of, 2 56 29 6 71
Factor V and Factor Viii, Combined Deficiency of 56 13 71
F5f8d2 56 73
F5f8d 58 54
Deficiency, Combined, Factor V and Factor Viii, Type 2 39
Combined Deficiency of Factor V and Factor Viii 58
Familial Multiple Coagulation Factor Deficiency 58
Factor V and Factor Viii Combined Deficiency 2 73
Multiple Coagulation Factor Deficiency 2 73
Fv and Fviii Combined Deficiency 58
Mcfd2 73

Characteristics:

Orphanet epidemiological data:

58
combined deficiency of factor v and factor viii
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Europe); Age of onset: All ages; Age of death: any age;

HPO:

31
factor v and factor viii, combined deficiency of, 2:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

OMIM 56 613625
MeSH 43 D025861
ICD10 via Orphanet 33 D68.8
UMLS via Orphanet 72 C1856883
Orphanet 58 ORPHA35909
MedGen 41 C3150889
UMLS 71 C1856883 C3150889

Summaries for Factor V and Factor Viii, Combined Deficiency of, 2

OMIM : 56 Combined deficiency of factor V (612309) and factor VIII (300841) is characterized by bleeding symptoms similar to those in hemophilia (306700) or parahemophilia (227400), caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma FV and FVIII antigen and activity levels are in the range of 5 to 30%. Inheritance of F5F8D is autosomal recessive and distinct from the coinheritance of FV deficiency and FVIII deficiency (summary by Zhang and Ginsburg, 2004). (613625)

MalaCards based summary : Factor V and Factor Viii, Combined Deficiency of, 2, also known as factor v and factor viii, combined deficiency of, is related to factor x deficiency and hemarthrosis. An important gene associated with Factor V and Factor Viii, Combined Deficiency of, 2 is MCFD2 (Multiple Coagulation Factor Deficiency 2, ER Cargo Receptor Complex Subunit), and among its related pathways/superpathways are Metabolism of proteins and Vesicle-mediated transport. Affiliated tissues include liver, and related phenotypes are epistaxis and reduced factor viii activity

UniProtKB/Swiss-Prot : 73 Factor V and factor VIII combined deficiency 2: A blood coagulation disorder characterized by bleeding symptoms similar to those in hemophilia or parahemophilia, that are caused by single deficiency of FV or FVIII, respectively. The most common symptoms are epistaxis, menorrhagia, and excessive bleeding during or after trauma. Plasma levels of coagulation factors V and VIII are in the range of 5 to 30% of normal.

Related Diseases for Factor V and Factor Viii, Combined Deficiency of, 2

Diseases related to Factor V and Factor Viii, Combined Deficiency of, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 49)
# Related Disease Score Top Affiliating Genes
1 factor x deficiency 31.6 MCFD2 F5
2 hemarthrosis 31.3 MCFD2 F8
3 afibrinogenemia, congenital 30.8 MCFD2 F8 F5
4 prothrombin deficiency 30.6 MCFD2 LMAN1 F8
5 brachydactyly, type d 30.6 MCFD2 LMAN1 F8
6 factor v deficiency 30.1 MCFD2 LMAN1 F8 F5
7 factor xiii deficiency 30.1 MCFD2 LMAN1 F8 F5
8 von willebrand's disease 29.4 F8 F5
9 factor viii deficiency 28.8 MCFD2 LMAN1 F8 F5
10 factor v and factor viii, combined deficiency of, 1 13.0
11 factor v and factor viii, combined deficiency of, with normal protein c and protein c inhibitor 12.8
12 vitamin k-dependent clotting factors, combined deficiency of, 1 12.3
13 factor vii and factor viii, combined deficiency of 12.1
14 factor viii and factor ix, combined deficiency of 12.1
15 factor ix and factor xi, combined deficiency of 12.1
16 factors viii, ix and xi, combined deficiency of 12.0
17 vitamin k-dependent clotting factors, combined deficiency of, 2 11.4
18 coumarin resistance 11.1
19 good syndrome 11.1
20 hemophilia a 10.4
21 autosomal recessive disease 10.4
22 hemophilia 10.3
23 rare hemorrhagic disorder 10.2
24 epidermodysplasia verruciformis 1 10.1
25 ichthyosis 10.1
26 placental abruption 10.1
27 ichthyosis, acquired 10.1
28 acquired hemophilia 9.8 F8 F5
29 acquired hemophilia a 9.7 F8 F5
30 post-thrombotic syndrome 9.7 F8 F5
31 sneddon syndrome 9.7 F8 F5
32 intracranial thrombosis 9.7 F8 F5
33 thrombosis 9.7 F8 F5
34 thrombophilia due to activated protein c resistance 9.7 F8 F5
35 thrombophilia 9.7 F8 F5
36 carotid artery occlusion 9.7 F8 F5
37 thrombophlebitis 9.7 F8 F5
38 central retinal vein occlusion 9.7 F8 F5
39 factor xi deficiency 9.7 F8 F5
40 inherited blood coagulation disease 9.7 F8 F5
41 blood coagulation disease 9.7 F8 F5
42 pulmonary artery disease 9.6 F8 F5
43 retinal artery occlusion 9.6 F8 F5
44 protein s deficiency 9.6 F8 F5
45 thrombophilia due to thrombin defect 9.6 F8 F5
46 vein disease 9.6 F8 F5
47 hemorrhagic disease 9.5 F8 F5
48 pulmonary embolism 9.4 F8 F5
49 cerebrovascular disease 9.2 F8 F5

Graphical network of the top 20 diseases related to Factor V and Factor Viii, Combined Deficiency of, 2:



Diseases related to Factor V and Factor Viii, Combined Deficiency of, 2

Symptoms & Phenotypes for Factor V and Factor Viii, Combined Deficiency of, 2

Human phenotypes related to Factor V and Factor Viii, Combined Deficiency of, 2:

58 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 epistaxis 58 31 Frequent (79-30%) HP:0000421
2 reduced factor viii activity 58 31 Very frequent (99-80%) HP:0003125
3 menorrhagia 58 31 Occasional (29-5%) HP:0000132
4 reduced coagulation factor v activity 58 31 Very frequent (99-80%) HP:0003225
5 hyperuricemia 58 Very rare (<4-1%)
6 gingival bleeding 58 Frequent (79-30%)
7 hematuria 58 Occasional (29-5%)
8 gastrointestinal hemorrhage 58 Occasional (29-5%)
9 intracranial hemorrhage 58 Occasional (29-5%)
10 hyperlipidemia 58 Very rare (<4-1%)
11 bruising susceptibility 58 Frequent (79-30%)
12 prolonged partial thromboplastin time 58 Very frequent (99-80%)
13 persistent bleeding after trauma 31 HP:0001934
14 prolonged bleeding after surgery 58 Occasional (29-5%)
15 joint hemorrhage 58 Occasional (29-5%)
16 prolonged bleeding following circumcision 58 Frequent (79-30%)
17 prolonged prothrombin time 58 Very frequent (99-80%)
18 prolonged bleeding after dental extraction 58 Frequent (79-30%)
19 bleeding with minor or no trauma 58 Frequent (79-30%)

Clinical features from OMIM:

613625

Drugs & Therapeutics for Factor V and Factor Viii, Combined Deficiency of, 2

Search Clinical Trials , NIH Clinical Center for Factor V and Factor Viii, Combined Deficiency of, 2

Genetic Tests for Factor V and Factor Viii, Combined Deficiency of, 2

Genetic tests related to Factor V and Factor Viii, Combined Deficiency of, 2:

# Genetic test Affiliating Genes
1 Factor V and Factor Viii, Combined Deficiency of, 2 29 MCFD2

Anatomical Context for Factor V and Factor Viii, Combined Deficiency of, 2

MalaCards organs/tissues related to Factor V and Factor Viii, Combined Deficiency of, 2:

40
Liver

Publications for Factor V and Factor Viii, Combined Deficiency of, 2

Articles related to Factor V and Factor Viii, Combined Deficiency of, 2:

(show all 45)
# Title Authors PMID Year
1
Genotype-phenotype correlation in combined deficiency of factor V and factor VIII. 54 61 56 6
18391077 2008
2
Bleeding due to disruption of a cargo-specific ER-to-Golgi transport complex. 54 61 56 6
12717434 2003
3
Combined deficiency of factor V and factor VIII is due to mutations in either LMAN1 or MCFD2. 54 61 56
16304051 2006
4
Familial multiple coagulation factor deficiencies: new biologic insight from rare genetic bleeding disorders. 54 61 56
15333032 2004
5
Mutations in the ER-Golgi intermediate compartment protein ERGIC-53 cause combined deficiency of coagulation factors V and VIII. 6
9546392 1998
6
Linkage of combined factors V and VIII deficiency to chromosome 18q by homozygosity mapping. 6
9045860 1997
7
[Congenital factor V deficiency (parahemophilia) with true hemophilia in two brothers]. 6
13229969 1954
8
Structural basis for the cooperative interplay between the two causative gene products of combined factor V and factor VIII deficiency. 54 61
20142513 2010
9
Crystal structure of the LMAN1-CRD/MCFD2 transport receptor complex provides insight into combined deficiency of factor V and factor VIII. 54 61
20138881 2010
10
[Combined deficiency of factors V and VIII caused by a novel compound heterozygous mutation of gene Lman1]. 54 61
20137144 2010
11
EF-hand domains of MCFD2 mediate interactions with both LMAN1 and coagulation factor V or VIII. 54 61
20007547 2010
12
A novel missense mutation causing abnormal LMAN1 in a Japanese patient with combined deficiency of factor V and factor VIII. 54 61
19787799 2009
13
A review of ERGIC-53: its structure, functions, regulation and relations with diseases. 54 61
19609866 2009
14
Combined Factor V and Factor VIII Deficiency. 54 61
19598067 2009
15
Recent developments in the understanding of the combined deficiency of FV and FVIII. 54 61
19183188 2009
16
Combined FV and FVIII deficiency. 54 61
19141160 2008
17
New insights into multiple coagulation factor deficiency from the solution structure of human MCFD2. 54 61
18590741 2008
18
The first case of combined coagulation factor V and coagulation factor VIII deficiency in Poland due to a novel p.Tyr135Asn missense mutation in the MCFD2 gene. 54 61
18685427 2008
19
Deletion of 3 residues from the C-terminus of MCFD2 affects binding to ERGIC-53 and causes combined factor V and factor VIII deficiency. 54 61
17971482 2008
20
The sugar-binding ability of ERGIC-53 is enhanced by its interaction with MCFD2. 54 61
18056485 2008
21
Combined factors V and VIII deficiency (F5F8D) in a Chinese family due to compound heterozygosity for nonsense mutations of the LMAN1 gene. 54 61
17910641 2007
22
Mutations in the MCFD2 gene are predominant among patients with hereditary combined FV and FVIII deficiency (F5F8D) in India. 54 61
17610559 2007
23
A new case of combined factor V and factor VIII deficiency further suggests that the LMAN1 M1T mutation is a frequent cause in Italian patients. 54 61
17287640 2007
24
Combined factor V - factor VIII deficiency (F5F8D): compound heterozygosity for two novel truncating mutations in LMAN1 in a consanguineous patient. 54 61
16676083 2006
25
Mutations in the MCFD2 gene and a novel mutation in the LMAN1 gene in Indian families with combined deficiency of factor V and VIII. 54 61
16044454 2005
26
Combined factor V and factor VIII deficiency in a Thai patient: a case report of genotype and phenotype characteristics. 54 61
15876275 2005
27
Molecular analysis of the ERGIC-53 gene in 35 families with combined factor V-factor VIII deficiency. 54 61
10090934 1999
28
The locus for combined factor V-factor VIII deficiency (F5F8D) maps to 18q21, between D18S849 and D18S1103. 54 61
9245995 1997
29
Low factor V level ameliorates bleeding diathesis in patients with combined deficiency of factor V and factor VIII. 61
31558466 2019
30
[Congenital factor V and factor VIII deficiency discovered in an elderly patient with abnormal bleeding after trauma]. 61
29743396 2018
31
Congenital factor V and VIII deficiency in women: a systematic review of literature and report of two new cases. 61
26376169 2016
32
Congenital combined deficiency of coagulation factors: a study of seven patients. 61
25215615 2015
33
Combined FV and FVIII deficiency (F5F8D) in a Chinese family with a novel missense mutation in MCFD2 gene. 61
25354775 2014
34
Successful Pregnancy in a Patient with Combined Deficiency of Factor V and Factor VIII. 61
24883216 2014
35
Combined deficiency of coagulation factors V and VIII: an update. 61
23852824 2013
36
Multiple coagulation factor deficiency protein 2 contains the ability to support stem cell self-renewal. 61
23660967 2013
37
Structural characterization of carbohydrate binding by LMAN1 protein provides new insight into the endoplasmic reticulum export of factors V (FV) and VIII (FVIII). 61
23709226 2013
38
Successful percutaneous coronary intervention in a patient with combined deficiency of FV and FVIII due to novel compound heterozygous mutations in LMAN1. 61
23557496 2013
39
The COPII pathway and hematologic disease. 61
22586181 2012
40
Unveiling the unfolding pathway of F5F8D disorder-associated D81H/V100D mutant of MCFD2 via multiple molecular dynamics simulations. 61
22208273 2012
41
Analysis of newly detected mutations in the MCFD2 gene giving rise to combined deficiency of coagulation factors V and VIII. 61
21492322 2011
42
Mice deficient in LMAN1 exhibit FV and FVIII deficiencies and liver accumulation of α1-antitrypsin. 61
21795745 2011
43
Two new mutations at ERGIC-53 gene in a Turkish family. 61
20460353 2011
44
Inherited and acquired factor V deficiency. 61
21245750 2011
45
Molecular analysis in two Tunisian families with combined factor V and factor VIII deficiency. 61
20491958 2010

Variations for Factor V and Factor Viii, Combined Deficiency of, 2

ClinVar genetic disease variations for Factor V and Factor Viii, Combined Deficiency of, 2:

6 ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MCFD2 NM_001171506.2(MCFD2):c.309+1G>ASNV Pathogenic 2866 rs387906287 2:47134948-47134948 2:46907809-46907809
2 MCFD2 NM_001171506.2(MCFD2):c.103del (p.Gln35fs)deletion Pathogenic 2867 rs1253799389 2:47136208-47136208 2:46909069-46909069
3 MCFD2 NM_001171506.2(MCFD2):c.249del (p.Asp83fs)deletion Pathogenic 2868 rs1294221028 2:47135009-47135009 2:46907870-46907870
4 MCFD2 NM_001171506.2(MCFD2):c.265_272del (p.Asp89fs)deletion Pathogenic 2869 rs1558461545 2:47134986-47134993 2:46907847-46907854
5 MCFD2 NM_001171506.2(MCFD2):c.387C>G (p.Asp129Glu)SNV Pathogenic 2870 rs137852913 2:47132656-47132656 2:46905517-46905517
6 MCFD2 NM_001171506.2(MCFD2):c.407T>C (p.Ile136Thr)SNV Pathogenic 2871 rs137852914 2:47132636-47132636 2:46905497-46905497
7 MCFD2 NM_001171506.2(MCFD2):c.241G>T (p.Asp81Tyr)SNV Pathogenic 2872 rs78289603 2:47135017-47135017 2:46907878-46907878
8 MCFD2 NM_001171506.2(MCFD2):c.149+5G>ASNV Likely pathogenic 2865 rs387906286 2:47136157-47136157 2:46909018-46909018
9 MCFD2 NM_139279.6(MCFD2):c.47T>C (p.Leu16Pro)SNV Uncertain significance 800824 2:47136264-47136264 2:46909125-46909125

UniProtKB/Swiss-Prot genetic disease variations for Factor V and Factor Viii, Combined Deficiency of, 2:

73
# Symbol AA change Variation ID SNP ID
1 MCFD2 p.Asp129Glu VAR_019076 rs137852913
2 MCFD2 p.Ile136Thr VAR_019077 rs137852914
3 MCFD2 p.Asp81His VAR_072245 rs78289603
4 MCFD2 p.Tyr135Asn VAR_072246 rs748641905

Expression for Factor V and Factor Viii, Combined Deficiency of, 2

Search GEO for disease gene expression data for Factor V and Factor Viii, Combined Deficiency of, 2.

Pathways for Factor V and Factor Viii, Combined Deficiency of, 2

GO Terms for Factor V and Factor Viii, Combined Deficiency of, 2

Cellular components related to Factor V and Factor Viii, Combined Deficiency of, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 Golgi membrane GO:0000139 9.46 MCFD2 LMAN1 F8 F5
2 endoplasmic reticulum-Golgi intermediate compartment GO:0005793 9.37 MCFD2 LMAN1
3 platelet alpha granule lumen GO:0031093 9.32 F8 F5
4 ER to Golgi transport vesicle membrane GO:0012507 9.26 MCFD2 LMAN1
5 COPII-coated ER to Golgi transport vesicle GO:0030134 9.13 LMAN1 F8 F5
6 endoplasmic reticulum-Golgi intermediate compartment membrane GO:0033116 8.92 MCFD2 LMAN1 F8 F5

Biological processes related to Factor V and Factor Viii, Combined Deficiency of, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 platelet degranulation GO:0002576 9.37 F8 F5
2 blood coagulation GO:0007596 9.33 LMAN1 F8 F5
3 hemostasis GO:0007599 9.32 F8 F5
4 protein N-linked glycosylation via asparagine GO:0018279 9.26 MCFD2 LMAN1
5 ER to Golgi vesicle-mediated transport GO:0006888 9.26 MCFD2 LMAN1 F8 F5
6 COPII vesicle coating GO:0048208 8.92 MCFD2 LMAN1 F8 F5

Molecular functions related to Factor V and Factor Viii, Combined Deficiency of, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 metal ion binding GO:0046872 9.26 MCFD2 LMAN1 F8 F5
2 copper ion binding GO:0005507 8.62 F8 F5

Sources for Factor V and Factor Viii, Combined Deficiency of, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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