HMWK DEFICIENCY
MCID: HGH020
MIFTS: 38

High Molecular Weight Kininogen Deficiency (HMWK DEFICIENCY)

Categories: Blood diseases, Genetic diseases, Rare diseases

Aliases & Classifications for High Molecular Weight Kininogen Deficiency

MalaCards integrated aliases for High Molecular Weight Kininogen Deficiency:

Name: High Molecular Weight Kininogen Deficiency 57 12 20 72 29 6 15 39 70
Hmwk Deficiency 57 12 72
Congenital High-Molecular-Weight Kininogen Deficiency 12 58
Flaujeac Factor Deficiency 20 44
Fitzgerald Trait 57 12
High-Molecular-Weight Kininogen Deficiency, Congenital 20
Kininogen Deficiency, High Molecular Weight 57
Kininogen Deficiency 57
Hmwk 20

Characteristics:

Orphanet epidemiological data:

58
congenital high-molecular-weight kininogen deficiency
Inheritance: Autosomal recessive;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive


HPO:

31
high molecular weight kininogen deficiency:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare haematological diseases


External Ids:

Disease Ontology 12 DOID:0111676
OMIM® 57 228960
MeSH 44 C537060
NCIt 50 C98946
SNOMED-CT 67 27312002
ICD10 via Orphanet 33 D68.8
UMLS via Orphanet 71 C0272340
Orphanet 58 ORPHA483
SNOMED-CT via HPO 68 258211005 409675001
UMLS 70 C0272340

Summaries for High Molecular Weight Kininogen Deficiency

OMIM® : 57 High molecular weight kininogen (HMWK) deficiency is an autosomal recessive coagulation defect. It is known by a variety of names, including Fitzgerald trait, Flaujeac trait, and Williams trait. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface-mediated activation of fibrinolysis. Fitzgerald trait represents a 'true' deficiency of HMWK, whereas Flaujeac and Williams traits represent total kininogen deficiency, in which both HMWK and low molecular weight kininogen (LMWK) are deficient. HMWK and LMWK are both encoded by the KNG1 gene (612358) (Bick, 2002; Takagaki et al., 1985). (228960) (Updated 05-Apr-2021)

MalaCards based summary : High Molecular Weight Kininogen Deficiency, also known as hmwk deficiency, is related to thrombosis and adenocarcinoma. An important gene associated with High Molecular Weight Kininogen Deficiency is KNG1 (Kininogen 1), and among its related pathways/superpathways are Response to elevated platelet cytosolic Ca2+ and Collagen chain trimerization. Affiliated tissues include endothelial, and related phenotypes are prolonged partial thromboplastin time and reduced kininogen activity

Disease Ontology : 12 A blood coagulation disease characterized by deficiency of high molecular weight kininogen but not of low molecular weight kininogen resulting in abnormal surface-mediated activation of fibrinolysis that has material basis in homozygous or compound heterozygous mutation in KNG1 on chromosome 3q27.3. Both high and low molecular weight kininogen are encoded by KNG1.

UniProtKB/Swiss-Prot : 72 High molecular weight kininogen deficiency: Autosomal recessive coagulation defect. Patients with HWMK deficiency do not have a hemorrhagic tendency, but they exhibit abnormal surface- mediated activation of fibrinolysis.

Wikipedia : 73 High-molecular-weight kininogen (HMWK or HK) is a circulating plasma protein which participates in the... more...

Related Diseases for High Molecular Weight Kininogen Deficiency

Diseases related to High Molecular Weight Kininogen Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 thrombosis 29.3 F3 F12 F11
2 adenocarcinoma 10.1
3 enterocolitis 10.0
4 prekallikrein deficiency 10.0
5 acquired hemophilia 10.0 F3 F11
6 acquired hemophilia a 10.0 F3 F11
7 prothrombin deficiency 10.0 F3 F11
8 angina pectoris 9.9 KNG1 F3
9 carotid artery thrombosis 9.9 F3 F11
10 bladder cancer 9.9
11 suppression of tumorigenicity 12 9.9
12 transitional cell carcinoma 9.9
13 hemarthrosis 9.9 F3 F11
14 shwartzman phenomenon 9.9 F3 F12
15 intracranial thrombosis 9.9 F3 F11
16 factor x deficiency 9.9 F3 F11
17 pulmonary artery disease 9.9 F3 F11
18 akinetopsia 9.9 KNG1 KLK4
19 von willebrand's disease 9.9 F3 F11
20 atherosclerosis susceptibility 9.9
21 proteasome-associated autoinflammatory syndrome 1 9.9
22 asthma 9.9
23 cerebral artery occlusion 9.9
24 pleurisy 9.9
25 aortic aneurysm 9.9
26 fatty liver disease 9.9
27 factor viii deficiency 9.9 F3 F11
28 hereditary angioedema 9.9 KNG1 KLKB1 F12
29 angioedema 9.8 KNG1 KLKB1 F12
30 hemophilia b 9.8 F3 F11
31 peripheral vascular disease 9.8 KNG1 F3
32 afibrinogenemia, congenital 9.8 F3 F11
33 occlusion precerebral artery 9.8 KNG1 F3 F11
34 blood coagulation disease 9.8 KNG1 F3 F11
35 thrombophilia 9.7 F3 F11
36 hemorrhagic disease 9.7 KNG1 F3 F11
37 renal hypertension 9.7 KNG1 KLKB1 KLK4
38 patent foramen ovale 9.6 F3 F12
39 liver cirrhosis 9.5 KNG1 KLKB1 F3 APTR
40 factor xi deficiency 9.5 KNG1 F3 F12 F11
41 congenital nonspherocytic hemolytic anemia 9.5 KNG1 KLKB1 KLK4 F11
42 c1 inhibitor deficiency 9.4 KNG1 KLKB1 KLK4 F12
43 pyruvate kinase deficiency of red cells 9.1 KNG1 KLKB1 KLK4 F3 F11
44 hypertension, essential 9.1 KNG1 KLKB1 KLK4 F3 F12
45 factor xii deficiency 8.8 KNG1 KLKB1 KLK4 F3 F12 F11

Graphical network of the top 20 diseases related to High Molecular Weight Kininogen Deficiency:



Diseases related to High Molecular Weight Kininogen Deficiency

Symptoms & Phenotypes for High Molecular Weight Kininogen Deficiency

Human phenotypes related to High Molecular Weight Kininogen Deficiency:

31
# Description HPO Frequency HPO Source Accession
1 prolonged partial thromboplastin time 31 HP:0003645
2 reduced kininogen activity 31 HP:0005527

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Lab:
prolonged partial thromboplastin time

Heme:
procoagulant deficiency
flaujeac factor deficiency
fitzgerald factor deficiency
williams factor deficiency
kininogen deficiency
more

Clinical features from OMIM®:

228960 (Updated 05-Apr-2021)

Drugs & Therapeutics for High Molecular Weight Kininogen Deficiency

Search Clinical Trials , NIH Clinical Center for High Molecular Weight Kininogen Deficiency

Cochrane evidence based reviews: flaujeac factor deficiency

Genetic Tests for High Molecular Weight Kininogen Deficiency

Genetic tests related to High Molecular Weight Kininogen Deficiency:

# Genetic test Affiliating Genes
1 High Molecular Weight Kininogen Deficiency 29 KNG1

Anatomical Context for High Molecular Weight Kininogen Deficiency

MalaCards organs/tissues related to High Molecular Weight Kininogen Deficiency:

40
Endothelial

Publications for High Molecular Weight Kininogen Deficiency

Articles related to High Molecular Weight Kininogen Deficiency:

(show all 32)
# Title Authors PMID Year
1
Molecular genetic survey of five Japanese families with high-molecular-weight kininogen deficiency. 61 6 57
1968772 1990
2
Characterization of molecular defects of Fitzgerald trait and another novel high-molecular-weight kininogen-deficient patient: insights into structural requirements for kininogen expression. 57 6
12576314 2003
3
Genetic basis of total kininogen deficiency in Williams' trait. 57 6
7901207 1993
4
Williams trait. Human kininogen deficiency with diminished levels of plasminogen proactivator and prekallikrein associated with abnormalities of the Hageman factor-dependent pathways. 6 57
1202089 1975
5
Fitzgerald factor: a hitherto unrecognised coagulation factor. 6 57
48123 1975
6
Isolated high-molecular-weight kininogen deficiency: a novel frameshift mutation in exon 10. 6 61
17522339 2007
7
A new case of high-molecular-weight kininogen inherited deficiency. 61 57
3728458 1986
8
Chromosomal mapping of human kininogen gene (KNG) to 3q26----qter. 57
1733668 1992
9
The human kininogen gene (KNG) mapped to chromosome 3q26-qter by analysis of somatic cell hybrids using the polymerase chain reaction. 57
2066106 1991
10
Cloning and sequence analysis of cDNAs for human high molecular weight and low molecular weight prekininogens. Primary structures of two human prekininogens. 57
2989293 1985
11
Decreased exercise tolerance and hypertension in severe hereditary deficiency of plasma kininogens. 57
6112306 1981
12
Prekallikrein deficiency in a kindred with kininogen deficiency and Fitzgerald trait clotting defect. Evidence that high molecular weight kininogen and prekallikrein exist as a complex in normal human plasma. 57
893663 1977
13
Flaujeac trait. Deficiency of human plasma kininogen. 57
127805 1975
14
A hitherto undescribed plasma factor acting at the contact phase of blood coagulation (Flaujeac factor): case report and coagulation studies. 57
1174709 1975
15
Fitzgerald Trait: Deficiency of a Hitherto Unrecognized Agent, Fitzgerald Factor, Participating in Surface-Mediated Reactions of Clotting, Fibrinolysis, Generation of Kinins, and the Property of Diluted Plasma Enhancing Vascular Permeability (PF/Dil). 57
16695963 1975
16
Severe high-molecular-weight kininogen deficiency due to a homozygous c.1456C > T nonsense variant in a large Chinese family. 61
32185598 2020
17
The First Korean Case of High-Molecular-Weight Kininogen Deficiency, With a Novel Variant, c.488delG, in the KNG1 Gene. 61
31858768 2020
18
Antithrombotic potential of the contact activation pathway. 61
27380557 2016
19
[Review of patients studied for coagulopathy in a Hematology/Oncology unit]. 61
26006274 2016
20
A novel frameshift mutation in exon 4 causing a deficiency of high-molecular-weight kininogen in a patient with splenic infarction. 61
24492696 2014
21
High molecular weight kininogen deficiency: a patient who underwent cardiac surgery. 61
11246531 2001
22
[High molecular weight kininogen deficiency]. 61
9833535 1998
23
[Coagulation and fibrinolysis associated with contact phase in plasma with high molecular weight kininogen deficiency]. 61
2593236 1989
24
[The fifth case of high molecular weight kininogen deficiency in Japan]. 61
3246722 1988
25
[A case of high molecular weight kininogen deficiency--problem of its laboratory diagnosis and low molecular weight kininogen]. 61
3324605 1987
26
Fitzgerald factor deficiency in an Australian aborigine. 61
3574180 1987
27
Detection of in vitro and in vivo cleavage of high molecular weight kininogen in human plasma by immunoblotting with monoclonal antibodies. 61
3730610 1986
28
Tachibana trait: human high molecular weight kininogen deficiency with diminished levels of prekallikrein and low molecular weight kininogen. 61
3853954 1985
29
Evidence against collagen activation of platelet-associated factor XI as a mechanism for initiating intrinsic clotting. 61
451451 1979
30
Activated partial thromboplastin time and minor coagulopathies. 61
420168 1979
31
Interactions among Hageman factor (HG, Factor XII), plasma thromboplastin antecedent (PTA, Factor XI), plasma prekallikrein (PK, Fletcher factor) and high molecular weight kininogen (HMW-K, Fitzgerald factor) in blood coagulation. 61
517254 1979
32
Plasma thromboplastin antecedent (PTA, factor XI): a specific and sensitive radioimmunoassay. 61
884316 1977

Variations for High Molecular Weight Kininogen Deficiency

ClinVar genetic disease variations for High Molecular Weight Kininogen Deficiency:

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 KNG1 NM_001102416.3(KNG1):c.1493del (p.Lys498fs) Deletion Affects 573 rs797044429 GRCh37: 3:186459677-186459677
GRCh38: 3:186741888-186741888
2 KNG1 NM_000893.4(KNG1):c.1126-538_1126-512delinsGGTGGTGGTGGTGGTGGTTTGTTTTTGG Indel Affects 574 rs869320718 GRCh37: 3:186458773-186458799
GRCh38: 3:186740984-186741010
3 KNG1 NM_001102416.3(KNG1):c.1216dup (p.His406fs) Duplication Affects 575 rs797044430 GRCh37: 3:186459397-186459398
GRCh38: 3:186741608-186741609
4 KNG1 NM_001102416.3(KNG1):c.586C>T (p.Arg196Ter) SNV Pathogenic 572 rs121918131 GRCh37: 3:186445047-186445047
GRCh38: 3:186727258-186727258
5 KNG1 NM_001102416.3(KNG1):c.1866_1869del (p.Ser623fs) Deletion Uncertain significance 225401 rs559129841 GRCh37: 3:186460048-186460051
GRCh38: 3:186742259-186742262

Expression for High Molecular Weight Kininogen Deficiency

Search GEO for disease gene expression data for High Molecular Weight Kininogen Deficiency.

Pathways for High Molecular Weight Kininogen Deficiency

GO Terms for High Molecular Weight Kininogen Deficiency

Cellular components related to High Molecular Weight Kininogen Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 extracellular space GO:0005615 9.35 KNG1 KLKB1 F3 F12 F11
2 collagen-containing extracellular matrix GO:0062023 9.33 KNG1 F3 F12
3 extracellular region GO:0005576 9.1 KNG1 KLKB1 KLK4 F3 F12 F11

Biological processes related to High Molecular Weight Kininogen Deficiency according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 proteolysis GO:0006508 9.73 KLKB1 KLK4 F12 F11
2 blood coagulation GO:0007596 9.65 KNG1 KLKB1 F3 F12 F11
3 protein processing GO:0016485 9.49 F3 F12
4 extracellular matrix disassembly GO:0022617 9.48 KLKB1 KLK4
5 zymogen activation GO:0031638 9.46 KLKB1 F12
6 fibrinolysis GO:0042730 9.4 KLKB1 F12
7 plasminogen activation GO:0031639 9.37 KLKB1 F11
8 positive regulation of fibrinolysis GO:0051919 9.33 KLKB1 F12 F11
9 Factor XII activation GO:0002542 9.32 KLKB1 F12
10 blood coagulation, intrinsic pathway GO:0007597 9.26 KNG1 KLKB1 F12 F11
11 hemostasis GO:0007599 9.02 KNG1 KLKB1 F3 F12 F11

Molecular functions related to High Molecular Weight Kininogen Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peptidase activity GO:0008233 9.46 KLKB1 KLK4 F12 F11
2 serine-type peptidase activity GO:0008236 9.26 KLKB1 KLK4 F12 F11
3 serine-type endopeptidase activity GO:0004252 9.02 KLKB1 KLK4 F3 F12 F11

Sources for High Molecular Weight Kininogen Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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