MCID: PRT129
MIFTS: 49

Prothrombin Deficiency, Congenital

Categories: Genetic diseases, Blood diseases, Rare diseases

Aliases & Classifications for Prothrombin Deficiency, Congenital

MalaCards integrated aliases for Prothrombin Deficiency, Congenital:

Name: Prothrombin Deficiency, Congenital 57 29 6
Dysprothrombinemia 57 76 59 75 13 55
Hypoprothrombinemia 57 76 59 75
Prothrombin Deficiency 59 75
Factor Ii Deficiency 75 73
Hereditary Factor Ii Deficiency Disease 73
Congenital Prothrombin Deficiency 37
Congenital Factor Ii Deficiency 59
Inherited Factor Ii Deficiency 73
Hypoprothrombinemias 55
Fa2d 75

Characteristics:

Orphanet epidemiological data:

59
congenital factor ii deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Europe); Age of onset: All ages; Age of death: any age;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
onset at birth
prevalence of true hypoprothrombinemia is 1 in 2 million
bleeding after trauma or surgery
some heterozygous carriers may have mild manifestations


HPO:

32
prothrombin deficiency, congenital:
Onset and clinical course variable expressivity congenital onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 613679
Orphanet 59 ORPHA325
ICD10 via Orphanet 34 D68.2
UMLS via Orphanet 74 C0272317 C0020640 C3203356
MeSH 44 D007020
KEGG 37 H01254

Summaries for Prothrombin Deficiency, Congenital

OMIM : 57 Prothrombin deficiency is an extremely rare autosomal recessive bleeding disorder characterized by low levels of circulating prothrombin; it affects about 1 in 2,000,000 individuals. There are 2 main types: type I deficiency, known as true prothrombin deficiency or 'hypoprothrombinemia,' is defined as plasma levels of prothrombin being less than 10% of normal with a concomitant decrease in activity. These patients have severe bleeding from birth, including umbilical cord hemorrhage, hematomas, ecchymoses, hematuria, mucosal bleeding, hemarthroses, intracranial bleeding, gastrointestinal bleeding, and menorrhagia. Type II deficiency, known as 'dysprothrombinemia,' is characterized by normal or low-normal synthesis of a dysfunctional protein. Bleeding symptoms are more variable, depending on the amount of residual functional activity. Variant prothrombin gene alleles can result in 'hypoprothrombinemia' or 'dysprothrombinemia,' and individuals who are compound heterozygous for these 2 types of alleles have variable manifestations. Heterozygous mutation carriers, who have plasma levels between 40 and 60% of normal, are usually asymptomatic, but can show bleeding after tooth extraction or surgical procedures (review by Lancellotti and De Cristofaro, 2009). (613679)

MalaCards based summary : Prothrombin Deficiency, Congenital, also known as dysprothrombinemia, is related to prothrombin deficiency and intestinal impaction. An important gene associated with Prothrombin Deficiency, Congenital is F2 (Coagulation Factor II, Thrombin), and among its related pathways/superpathways are Complement and coagulation cascades and Response to elevated platelet cytosolic Ca2+. The drugs Warfarin and Liver Extracts have been mentioned in the context of this disorder. Affiliated tissues include liver, and related phenotypes are menorrhagia and gingival bleeding

UniProtKB/Swiss-Prot : 75 Factor II deficiency: A very rare blood coagulation disorder characterized by mucocutaneous bleeding symptoms. The severity of the bleeding manifestations correlates with blood factor II levels.

Wikipedia : 76 Thrombin (EC 3.4.21.5, fibrinogenase, thrombase, thrombofort, topical, thrombin-C, tropostasin,... more...

Related Diseases for Prothrombin Deficiency, Congenital

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

(show top 50) (show all 116)
# Related Disease Score Top Affiliating Genes
1 prothrombin deficiency 27.6 APOH F2 F5 SERPINC1
2 intestinal impaction 10.3 F2 SERPINC1
3 fournier gangrene 10.3 F2 SERPINC1
4 blood protein disease 10.3 F2 SERPINC1
5 alpha-2-plasmin inhibitor deficiency 10.3 F2 SERPINC1
6 giant hemangioma 10.3 F2 SERPINC1
7 blue toe syndrome 10.3 F2 SERPINC1
8 intracranial embolism 10.3 F2 SERPINC1
9 anterior spinal artery syndrome 10.3 F2 SERPINC1
10 subendocardial myocardial infarction 10.3 F2 SERPINC1
11 marantic endocarditis 10.3 F2 SERPINC1
12 purpura fulminans 10.2 F2 SERPINC1
13 korean hemorrhagic fever 10.2 F2 SERPINC1
14 heparin-induced thrombocytopenia 10.2 F10 SERPINC1
15 esophageal varix 10.2 F2 SERPINC1
16 inherited blood coagulation disease 10.2 F2 SERPINC1
17 hypersplenism 10.2 F2 SERPINC1
18 hemorrhagic fever 10.2 F2 SERPINC1
19 splenic infarction 10.2 APOH F2
20 hepatic vascular disease 10.2 F2 SERPINC1
21 papilledema 10.2 APOH F2
22 factor xi deficiency 10.1 F2 SERPINC1
23 buerger disease 10.1 APOH F2
24 factor vii deficiency 10.1 F10 F2
25 hepatitis a 10.1 F2 SERPINC1
26 osteonecrosis 10.0 F2 SERPINC1
27 infective endocarditis 10.0 APOH F2
28 pulmonary edema 10.0 F2 SERPINC1
29 paracetamol poisoning 10.0 F2 F5
30 thrombocytosis 10.0 F2 SERPINC1
31 hemoglobin e disease 9.9 F2 F5
32 cryptogenic cirrhosis 9.9 F2 F5
33 factor viii deficiency 9.9 F2 F5
34 porencephaly 9.9 F2 F5
35 acquired hemophilia 9.9 F10 F5
36 sticky platelet syndrome 9.9 F5 SERPINC1
37 peripheral vascular disease 9.9 F2 SERPINC1
38 arteritic anterior ischemic optic neuropathy 9.8 F2 F5
39 meningococcemia 9.8 F5 SERPINC1
40 may-thurner syndrome 9.8 APOH F5
41 acute liver failure 9.8 F2 F5
42 acanthamoeba keratitis 9.8 APOH F5
43 severe hemophilia a 9.8 F2 F5
44 leech infestation 9.8 F10 F2 SERPINC1
45 quebec platelet disorder 9.8 F10 F5
46 pregnancy loss, recurrent 1 9.8 APOH F5
47 legg-calve-perthes disease 9.8 F5 SERPINC1
48 hemophilia b 9.7 F10 F2 SERPINC1
49 thrombasthenia 9.7 F2 F5
50 hemophilia a 9.7 F10 F5

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



Diseases related to Prothrombin Deficiency, Congenital

Symptoms & Phenotypes for Prothrombin Deficiency, Congenital

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Nose:
epistaxis

Hematology:
prolonged bleeding time
prolonged prothrombin time
bleeding tendency due to defect in prothrombin and inability to form fibrin clot
prolonged activated partial thromboplastin time
decreased f2 antigen levels (in some patients)
more
Abdomen Gastrointestinal:
gastrointestinal bleeding

Muscle Soft Tissue:
hematomas
umbilical cord hemorrhage

Neurologic Central Nervous System:
intracranial bleeding

Head And Neck Mouth:
gingival bleeding

Genitourinary Internal Genitalia Female:
menorrhagia

Skin Nails Hair Skin:
ecchymosis
easy bruising

Skeletal:
hemarthroses


Clinical features from OMIM:

613679

Human phenotypes related to Prothrombin Deficiency, Congenital:

32 (show all 10)
# Description HPO Frequency HPO Source Accession
1 menorrhagia 32 HP:0000132
2 gingival bleeding 32 HP:0000225
3 epistaxis 32 HP:0000421
4 bruising susceptibility 32 HP:0000978
5 gastrointestinal hemorrhage 32 HP:0002239
6 prolonged bleeding time 32 HP:0003010
7 prolonged partial thromboplastin time 32 HP:0003645
8 joint hemorrhage 32 HP:0005261
9 prolonged prothrombin time 32 HP:0008151
10 reduced prothrombin activity 32 HP:0012201

MGI Mouse Phenotypes related to Prothrombin Deficiency, Congenital:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 homeostasis/metabolism MP:0005376 9.02 APOH F10 F2 F5 SERPINC1

Drugs & Therapeutics for Prothrombin Deficiency, Congenital

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

(show all 6)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Warfarin Approved Phase 1, Phase 2 81-81-2 6691 54678486
2 Liver Extracts Phase 2
3 Anticoagulants Phase 1, Phase 2
4 Anti-Bacterial Agents
5 Antibiotics, Antitubercular
6 Anti-Infective Agents

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Phase II, Double-blinded, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Vitalliver in Patients With Decompensated Cirrhosis Completed NCT00562783 Phase 2 Vitaliver;Placebo
2 Randomized Controlled Feasibility Trial of the Fearon Algorithm to Improve Management of Unstable Warfarin Terminated NCT02267408 Phase 1, Phase 2
3 Antibiotic-associated Coagulopathy Unknown status NCT02172833

Search NIH Clinical Center for Prothrombin Deficiency, Congenital

Inferred drug relations via UMLS 73 / NDF-RT 51 :


Genetic Tests for Prothrombin Deficiency, Congenital

Genetic tests related to Prothrombin Deficiency, Congenital:

# Genetic test Affiliating Genes
1 Prothrombin Deficiency, Congenital 29 F2

Anatomical Context for Prothrombin Deficiency, Congenital

MalaCards organs/tissues related to Prothrombin Deficiency, Congenital:

41
Liver

Publications for Prothrombin Deficiency, Congenital

Articles related to Prothrombin Deficiency, Congenital:

(show all 50)
# Title Authors Year
1
Bleeding manifestations in heterozygotes with prothrombin deficiency or abnormalities vs. unaffected family members as observed during a long follow-up study. ( 28665815 )
2017
2
A case of congenital prothrombin deficiency and idiopathic thrombocytopenic purpura in a pregnant female. ( 26886363 )
2016
3
Congenital prothrombin deficiency: an update. ( 23852823 )
2013
4
Two novel mutations in the prothrombin gene identified in a patient with compound heterozygous type 1/2 prothrombin deficiency. ( 23711336 )
2013
5
Prophylactic administration of prothrombin complex concentrates for congenital prothrombin deficiency with a novel frameshift mutation, prothrombin saitama. ( 23152198 )
2013
6
Prothrombin Mumbai causes severe prothrombin deficiency due to a novel Cys90Ser mutation. ( 22392504 )
2012
7
Prophylaxis in severe prothrombin deficiency. ( 20950404 )
2011
8
Hereditary prothrombin deficiency. ( 19750864 )
2009
9
Congenital prothrombin deficiency. ( 19598065 )
2009
10
True congenital prothrombin deficiency due to a 'new' mutation in the pre-propeptide (ARG-39 GLN). ( 18852482 )
2008
11
Acquired prothrombin deficiency in a patient with follicular lymphoma. ( 18355267 )
2008
12
Mutations are no substitutes for clotting, chromogenic and immunological assays in patients with congenital prothrombin deficiency. ( 18306360 )
2008
13
Severe prothrombin deficiency caused by prothrombin-Edmonton (R-4Q) combined with a previously undetected deletion. ( 17002658 )
2006
14
Prothrombin deficiency caused by compound heterozygosity for two novel mutations in the prothrombin gene associated with a bleeding tendency. ( 16543981 )
2006
15
The feasibility of total ankle prosthesis for severe arthropathy in haemophilia and prothrombin deficiency. ( 17083522 )
2006
16
Molecular genetics of hereditary prothrombin deficiency in Indian patients: identification of a novel Ala362 --&amp;gt; Thr (Prothrombin Vellore 1) mutation. ( 15892853 )
2005
17
Combined deficiency of protease-activated receptor-4 and fibrinogen recapitulates the hemostatic defect but not the embryonic lethality of prothrombin deficiency. ( 14504091 )
2004
18
Successful prophylactic treatment for bleeding in a girl with severe hereditary prothrombin deficiency using a prothrombin complex concentrate (Bebulin VH). ( 15284583 )
2004
19
A common mutation, Arg457--&amp;gt;Gln, links prothrombin deficiencies in the Puerto Rican population. ( 14629473 )
2003
20
[Prothrombin deficiency resulted from a homozygous Glu29 to Gly mutation in the prothrombin gene]. ( 14575584 )
2003
21
Bullous hematoma of the palm: an unusual complication of scabies in a child with congenital prothrombin deficiency. ( 12437569 )
2002
22
Rescue of prothrombin-deficiency by transgene expression in mice. ( 12529749 )
2002
23
Acquired bleeding disorder in a patient with malignant lymphoma: antibody-mediated prothrombin deficiency. ( 11241228 )
2001
24
Identification and three-dimensional structural analysis of nine novel mutations in patients with prothrombin deficiency. ( 11154146 )
2000
25
Hereditary prothrombin deficiency presenting as intracranial haematoma in infancy. ( 10706027 )
1999
26
Prothrombin deficiency results in embryonic and neonatal lethality in mice. ( 9636195 )
1998
27
Incomplete embryonic lethality and fatal neonatal hemorrhage caused by prothrombin deficiency in mice. ( 9636196 )
1998
28
Prothrombin deficiency and hemorrhage associated with a lupus anticoagulant. ( 8980268 )
1997
29
Transient lupus anticoagulant associated with prothrombin deficiency: unusual cause of bleeding in a 5-year-old girl. ( 7978060 )
1994
30
Detection of the carrier state in congenital &amp;quot;true&amp;quot; prothrombin deficiency. ( 3354565 )
1988
31
Concurrent lupus anticoagulants and prothrombin deficiency due to phenytoin use. ( 3115223 )
1987
32
Prothrombin Habana: a new dysfunctional molecule of human prothrombin associated with a true prothrombin deficiency. ( 6409139 )
1983
33
Prothrombin deficiency in a cocker spaniel. ( 6980872 )
1982
34
Prothrombin Molise: a &amp;quot;new&amp;quot; congenital dysprothrombinemia, double heterozygosis with an abnormal prothrombin and &amp;quot;true&amp;quot; prothrombin deficiency. ( 418829 )
1978
35
Bleeding disorder in an infant associated with anicteric hepatitis. Acquired prothrombin deficiency. ( 4434662 )
1974
36
Hereditary prothrombin deficiency. ( 4982446 )
1970
37
Christmas disease associated with prothrombin deficiency and thrombasthenia. ( 5350280 )
1969
38
Severe isolated prothrombin deficiency: an acquired state with complete recovery. ( 13962584 )
1962
39
The measurement of prothrombin in plasma; a case of prothrombin deficiency. ( 13034913 )
1953
40
CLINICO-pathological conference; diffuse nodular cirrhosis and subacute hepatitis; icterus; cerebral edema and probable prothrombin deficiency. ( 15434966 )
1950
41
Prothrombin deficiency of the newborn. ( 18129082 )
1949
42
The nature of the prothrombin deficiency in dicoumarin plasma. ( 18130447 )
1949
43
The Use of Synthetic Vitamin K Substitutes in the Treatment of Prothrombin Deficiency. ( 20322499 )
1942
44
CLINICAL SIGNIFICANCE OF PROTHROMBIN DEFICIENCY AND ITS TREATMENT. ( 17857921 )
1941
45
Prothrombin Deficiency in Disease of the Liver and Bile Passages, and its Treatment with Synthetic Vitamin K. ( 20783619 )
1941
46
HAEMORRHAGIC TENDENCY ASSOCIATED WITH PROTHROMBIN DEFICIENCY AND ITS TREATMENT WITH VITAMIN K AND BILE. ( 20321723 )
1940
47
PROTHROMBIN DEFICIENCY AND THE EFFECTS OF VITAMIN K IN OBSTRUCTIVE JAUNDICE AND BILIARY FISTULA. ( 17857347 )
1939
48
BLEEDING TENDENCY AND PROTHROMBIN DEFICIENCY IN BILIARY FISTULA DOGS: EFFECT OF FEEDING BILE AND VITAMIN K. ( 19870764 )
1938
49
PROTHROMBIN DEFICIENCY AND THE BLEEDING TENDENCY IN LIVER INJURY (CHLOROFORM INTOXICATION). ( 19870699 )
1937
50
PROTHROMBIN DEFICIENCY THE CAUSE OF BLEEDING IN BILE FISTULA DOGS. ( 19870504 )
1936

Variations for Prothrombin Deficiency, Congenital

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

75
# Symbol AA change Variation ID SNP ID
1 F2 p.Glu200Lys VAR_006711 rs62623459
2 F2 p.Arg314Cys VAR_006712 rs121918477
3 F2 p.Arg314His VAR_006713 rs754231232
4 F2 p.Met380Thr VAR_006714 rs121918481
5 F2 p.Arg425Cys VAR_006715 rs121918479
6 F2 p.Arg431His VAR_006716 rs121918482
7 F2 p.Arg461Trp VAR_006717 rs121918478
8 F2 p.Glu509Ala VAR_006718
9 F2 p.Gly601Val VAR_006719 rs121918480
10 F2 p.Glu72Gly VAR_055232

ClinVar genetic disease variations for Prothrombin Deficiency, Congenital:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 F2 NM_000506.4(F2): c.462_463insT (p.Asn155Terfs) insertion Pathogenic rs387906522 GRCh37 Chromosome 11, 46744971: 46744972
2 F2 NM_000506.4(F2): c.462_463insT (p.Asn155Terfs) insertion Pathogenic rs387906522 GRCh38 Chromosome 11, 46723421: 46723422
3 F2 NM_000506.4(F2): c.*97G> A single nucleotide variant Pathogenic rs1799963 GRCh37 Chromosome 11, 46761055: 46761055
4 F2 NM_000506.4(F2): c.*97G> A single nucleotide variant Pathogenic rs1799963 GRCh38 Chromosome 11, 46739505: 46739505
5 F2 F2, TYR44CYS single nucleotide variant Pathogenic

Expression for Prothrombin Deficiency, Congenital

Search GEO for disease gene expression data for Prothrombin Deficiency, Congenital.

Pathways for Prothrombin Deficiency, Congenital

Pathways related to Prothrombin Deficiency, Congenital according to KEGG:

37
# Name Kegg Source Accession
1 Complement and coagulation cascades hsa04610

Pathways related to Prothrombin Deficiency, Congenital according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.63 APOH F10 F2 F5 SERPINC1
2
Show member pathways
12.28 F10 F2 F5 SERPINC1
3
Show member pathways
11.46 F10 F2 F5 SERPINC1
4
Show member pathways
11.4 F10 F2
5 11.07 F10 F2 F5 SERPINC1
6 10.5 F10 F2

GO Terms for Prothrombin Deficiency, Congenital

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

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.46 APOH F2 F5 SERPINC1
2 extracellular region GO:0005576 9.35 APOH F10 F2 F5 SERPINC1
3 Golgi lumen GO:0005796 9.26 F10 F2
4 endoplasmic reticulum lumen GO:0005788 8.92 F10 F2 F5 SERPINC1

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

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 cellular protein metabolic process GO:0044267 9.63 F2 F5 SERPINC1
2 ER to Golgi vesicle-mediated transport GO:0006888 9.61 F10 F2 F5
3 blood coagulation GO:0007596 9.56 F10 F2 F5 SERPINC1
4 platelet degranulation GO:0002576 9.49 APOH F5
5 signal peptide processing GO:0006465 9.48 F10 F2
6 positive regulation of blood coagulation GO:0030194 9.4 APOH F2
7 peptidyl-glutamic acid carboxylation GO:0017187 9.37 F10 F2
8 blood coagulation, intrinsic pathway GO:0007597 9.33 APOH F10 F2
9 negative regulation of fibrinolysis GO:0051918 9.32 APOH F2
10 regulation of blood coagulation GO:0030193 9.13 APOH F2 SERPINC1
11 hemostasis GO:0007599 8.92 F10 F2 F5 SERPINC1

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

# Name GO ID Score Top Affiliating Genes
1 phospholipid binding GO:0005543 8.96 APOH F10
2 heparin binding GO:0008201 8.8 APOH F2 SERPINC1

Sources for Prothrombin Deficiency, Congenital

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 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 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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