Hageman factor deficiency

ハーゲマン因子欠乏症

WordNet

1. be a contributing factor; "make things factor into a companys profitability"
2. any of the numbers (or symbols) that form a product when multiplied together
3. an independent variable in statistics
4. anything that contributes causally to a result; "a number of factors determined the outcome"
5. consider as relevant when making a decision; "You must factor in the recent developments" (同)factor in, factor out
6. resolve into factors; "a quantum computer can factor the number 15" (同)factor in, factor out
7. an event known to have happened or something known to have existed; "your fears have no basis in fact"; "how much of the story is fact and how much fiction is hard to tell"
8. a concept whose truth can be proved; "scientific hypotheses are not facts"
9. a piece of information about circumstances that exist or events that have occurred; "first you must collect all the facts of the case"
10. a statement or assertion of verified information about something that is the case or has happened; "he supported his argument with an impressive array of facts"

PrepTutorEJDIC

1. (…の)『要因』,(…を生み出す)要素《+『in』+『名』(do『ing』)》 / 囲数,約数 / 代理人,《おもに英》仲買人 / =factorize
2. 〈C〉『事実』,実際にある(あった)事 / 〈U〉真相,真実(truth) / 《the~》(法律用語で)犯行
3. 〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/28 21:26:58」(JST)

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Coagulation factor XII (Hageman factor)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 4BDW, 4BDX
Identifiers
Symbols	F12 ; HAE3; HAEX; HAF
External IDs	OMIM: 610619 MGI: 1891012 HomoloGene: 425 ChEMBL: 2821 GeneCards: F12 Gene
EC number	3.4.21.38
Gene ontology Molecular function • serine-type endopeptidase activity • protein binding • misfolded protein binding • serine-type aminopeptidase activity Cellular component • extracellular region • extracellular space • plasma membrane • extracellular vesicular exosome Biological process • plasma kallikrein-kinin cascade • Factor XII activation • proteolysis • blood coagulation • blood coagulation, intrinsic pathway • positive regulation of plasminogen activation • protein processing • protein autoprocessing • positive regulation of blood coagulation • zymogen activation • fibrinolysis • innate immune response • response to misfolded protein • positive regulation of fibrinolysis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	2161	58992
Ensembl	ENSG00000131187	ENSMUSG00000021492
UniProt	P00748	Q80YC5
RefSeq (mRNA)	NM_000505	NM_021489
RefSeq (protein)	NP_000496	NP_067464
Location (UCSC)	Chr 5: 176.83 – 176.84 Mb	Chr 13: 55.42 – 55.43 Mb
PubMed search	[1]	[2]

Coagulation factor XII, also known as Hageman factor, is a plasma protein. It is the zymogen form of factor XIIa, an enzyme (EC 3.4.21.38) of the serine protease (or serine endopeptidase) class. In humans, factor XII is encoded by the F12 gene.

Structure

Human Factor XII is 596 amino acids long and consists of two domains, the heavy chain (353 residues) and light chain (243 residues) held together by a disulfide bond. It is 80,000 daltons. Its heavy chain contains two fibronectin-type domains (type I and II), two epidermal growth factor-like domains, a kringle domain, and a proline-rich region, and its light chain contains the protease domain. Recently, the structure of the FnI-EGF-like tandem domain of coagulation factor XII was solved by x-ray crystallography.

Function

Factor XII is part of the coagulation cascade and activates factor XI and prekallikrein in vitro. Factor XII itself is activated to factor XIIa by negatively charged surfaces, such as glass. This is the starting point of the intrinsic pathway, which is now regarded as an obsolete term, because of the fact that there is no intrinsic pathway in vivo. Factor XII is only used to start coagulation cascades in laboratory studies and is considered to have little to no effect on coagulation in vivo.

The coagulation cascade.

In vivo, factor XII is activated by contact to polyanions. Activated platelets secrete inorganic polymers, polyphosphates. Contact to polyphosphates activates factor XII and initiates fibrin formation by the intrinsic pathway of coagulation with critical importance for thrombus formation. Targeting polyphosphates with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice. Addition of polyphosphates restored defective plasma clotting of Hermansky-Pudlak syndrome patients, indicating that the inorganic polymer is the endogenous factor XII activator in vivo. Platelet polyphosphate-driven factor XII activation provides the link from primary hemostasis (formation of a platelet plug) to secondary hemostasis (fibrin meshwork formation).

Genetics

The gene for factor XII is located on the tip of the long arm of the fifth chromosome (5q33-qter).

Role in disease

Factor XII deficiency is a rare disorder that is inherited in an autosomal recessive manner. Unlike other clotting factor deficiencies, factor XII deficiency is totally asymptomatic and does not cause excess bleeding. Mice lacking the gene for factor XII, however, are less susceptible to thrombosis. The protein seems to be involved in the later stages of clot formation rather than the first occlusion of damages in the blood vessel wall.

Factor XII does play an important role in clot formation during in vitro measurements of the partial thromboplastin time, which causes these measurements to be markedly prolonged in patients with factor XII deficiency, usually well beyond even what is seen in hemophilia A, hemophilia B, or factor XI deficiency. As a result, the main concern related to factor XII deficiency is the unnecessary testing, delay in care, worry, etc. that may be prompted by the abnormal lab result. All of this, including the mechanism of inheritance, also holds true for the other contact factors, prekallikrein (Fletcher factor) and high molecular weight kininogen.

Excess levels of factor XII can predispose individuals towards greater risk of venous thrombosis due to factor XII's role as one of the catalysts for conversion of plasminogen to its active fibrinolytic form of plasmin.

Factor XII is also activated by endotoxins, especially lipid A.

History

Hageman factor was first discovered in 1955 when a routine preoperative blood sample of the 37-year-old railroad brakeman John Hageman (1918) was found to have prolonged clotting time in test tubes, even though he had no hemorrhagic symptoms. Hageman was then examined by Dr. Oscar Ratnoff, who found that Mr. Hageman lacked a previously unidentified clotting factor. Dr. Ratnoff later found that the Hageman factor deficiency is an autosomal recessive disorder, after examining several related people who had the deficiency. Paradoxically, pulmonary embolism contributed to Hageman's death after an occupational accident. Since then, case studies and clinical studies identified an association between thrombosis and Factor XII deficiency. Hepatocytes express blood coagulation factor XII.

References

Further reading

• Girolami A, Randi ML, Gavasso S et al. (2005). "The occasional venous thromboses seen in patients with severe (homozygous) FXII deficiency are probably due to associated risk factors: a study of prevalence in 21 patients and review of the literature". J. Thromb. Thrombolysis 17 (2): 139–43. doi:10.1023/B:THRO.0000037670.42776.cd. PMID 15306750.  CS1 maint: Explicit use of et al. (link)
• Renné T, Gailani D (2007). "Role of Factor XII in hemostasis and thrombosis: clinical implications". Expert review of cardiovascular therapy 5 (4): 733–41. doi:10.1586/14779072.5.4.733. PMID 17605651. 
• Harris RJ, Ling VT, Spellman MW (1992). "O-linked fucose is present in the first epidermal growth factor domain of factor XII but not protein C". J. Biol. Chem. 267 (8): 5102–7. PMID 1544894. 
• McMullen BA, Fujikawa K, Davie EW (1991). "Location of the disulfide bonds in human plasma prekallikrein: the presence of four novel apple domains in the amino-terminal portion of the molecule". Biochemistry 30 (8): 2050–6. doi:10.1021/bi00222a007. PMID 1998666. 
• Miyata T, Kawabata S, Iwanaga S et al. (1989). "Coagulation factor XII (Hageman factor) Washington D.C.: inactive factor XIIa results from Cys-571----Ser substitution". Proc. Natl. Acad. Sci. U.S.A. 86 (21): 8319–22. doi:10.1073/pnas.86.21.8319. PMC 298272. PMID 2510163.  CS1 maint: Explicit use of et al. (link)
• Bernardi F, Marchetti G, Patracchini P et al. (1987). "Factor XII gene alteration in Hageman trait detected by TaqI restriction enzyme". Blood 69 (5): 1421–4. PMID 2882793.  CS1 maint: Explicit use of et al. (link)
• Cool DE, MacGillivray RT (1987). "Characterization of the human blood coagulation factor XII gene. Intron/exon gene organization and analysis of the 5'-flanking region". J. Biol. Chem. 262 (28): 13662–73. PMID 2888762. 
• Que BG, Davie EW (1986). "Characterization of a cDNA coding for human factor XII (Hageman factor)". Biochemistry 25 (7): 1525–8. doi:10.1021/bi00355a009. PMID 3011063. 
• Royle NJ, Nigli M, Cool D et al. (1988). "Structural gene encoding human factor XII is located at 5q33-qter". Somat. Cell Mol. Genet. 14 (2): 217–21. doi:10.1007/BF01534407. PMID 3162339.  CS1 maint: Explicit use of et al. (link)
• Citarella F, Tripodi M, Fantoni A et al. (1989). "Assignment of human coagulation factor XII (fXII) to chromosome 5 by cDNA hybridization to DNA from somatic cell hybrids". Hum. Genet. 80 (4): 397–8. doi:10.1007/BF00273661. PMID 3198120.  CS1 maint: Explicit use of et al. (link)
• Henry ML, Everson B, Ratnoff OD (1988). "Inhibition of the activation of Hageman factor (factor XII) by beta 2-glycoprotein I". J. Lab. Clin. Med. 111 (5): 519–23. PMID 3361230. 
• Chung DW, Fujikawa K, McMullen BA, Davie EW (1986). "Human plasma prekallikrein, a zymogen to a serine protease that contains four tandem repeats". Biochemistry 25 (9): 2410–7. doi:10.1021/bi00357a017. PMID 3521732. 
• Tripodi M, Citarella F, Guida S et al. (1986). "cDNA sequence coding for human coagulation factor XII (Hageman)". Nucleic Acids Res. 14 (7): 3146. doi:10.1093/nar/14.7.3146. PMC 339730. PMID 3754331.  CS1 maint: Explicit use of et al. (link)
• Cool DE, Edgell CJ, Louie GV et al. (1985). "Characterization of human blood coagulation factor XII cDNA. Prediction of the primary structure of factor XII and the tertiary structure of beta-factor XIIa". J. Biol. Chem. 260 (25): 13666–76. PMID 3877053.  CS1 maint: Explicit use of et al. (link)
• McMullen BA, Fujikawa K (1985). "Amino acid sequence of the heavy chain of human alpha-factor XIIa (activated Hageman factor)". J. Biol. Chem. 260 (9): 5328–41. PMID 3886654. 
• de Grouchy J, Turleau C (1975). "Tentative localization of a Hageman (Factor XII) locus on 7q, probably the 7q35 band". Humangenetik 24 (3): 197–200. doi:10.1007/bf00283584. PMID 4140832. 
• Fujikawa K, McMullen BA (1983). "Amino acid sequence of human beta-factor XIIa". J. Biol. Chem. 258 (18): 10924–33. PMID 6604055. 
• Hovinga JK, Schaller J, Stricker H et al. (1994). "Coagulation factor XII Locarno: the functional defect is caused by the amino acid substitution Arg 353-->Pro leading to loss of a kallikrein cleavage site". Blood 84 (4): 1173–81. PMID 8049433.  CS1 maint: Explicit use of et al. (link)
• Schloesser M, Hofferbert S, Bartz U et al. (1996). "The novel acceptor splice site mutation 11396(G-->A) in the factor XII gene causes a truncated transcript in cross-reacting material negative patients". Hum. Mol. Genet. 4 (7): 1235–7. doi:10.1093/hmg/4.7.1235. PMID 8528215.  CS1 maint: Explicit use of et al. (link)
• Hofferbert S, Müller J, Köstering H et al. (1996). "A novel 5'-upstream mutation in the factor XII gene is associated with a TaqI restriction site in an Alu repeat in factor XII-deficient patients". Hum. Genet. 97 (6): 838–41. doi:10.1007/BF02346200. PMID 8641707.  CS1 maint: Explicit use of et al. (link)

External links

• The MEROPS online database for peptidases and their inhibitors: S01.211
• Factor XII at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 静脈血栓症の原因の概要 overview of the causes of venous thrombosis
• 2. 出血性素因を有する成人患者へのアプローチ approach to the adult patient with a bleeding diathesis
• 3. 凝固検査の臨床使用 clinical use of coagulation tests
• 4. もやもや病：病因、臨床的特徴、および診断 moyamoya disease etiology clinical features and diagnosis
• 5. 不育症の定義および病因 definition and etiology of recurrent pregnancy loss

English Journal

• Presentation, diagnosis and treatment of angioedema without wheals: a retrospective analysis of a cohort of 1058 patients.

• Mansi M1, Zanichelli A, Coerezza A, Suffritti C, Wu MA, Vacchini R, Stieber C, Cichon S, Cicardi M.
• Journal of internal medicine.J Intern Med.2015 May;277(5):585-93. doi: 10.1111/joim.12304. Epub 2014 Sep 27.
• BACKGROUND: The first classification of angioedema without wheals was recently reported and comprises different forms of the disease distinguished by aetiology, mediator of oedema and inheritance.METHODS: In total, 1725 consecutive patients with angioedema without wheals were examined at our centre
• PMID 25196353

• Plasma contact system activation drives anaphylaxis in severe mast cell-mediated allergic reactions.

• Sala-Cunill A1, Björkqvist J2, Senter R3, Guilarte M4, Cardona V4, Labrador M4, Nickel KF5, Butler L5, Luengo O4, Kumar P2, Labberton L2, Long A6, Di Gennaro A2, Kenne E2, Jämsä A2, Krieger T6, Schlüter H6, Fuchs T5, Flohr S7, Hassiepen U7, Cumin F7, McCrae K8, Maas C9, Stavrou E10, Renné T11.
• The Journal of allergy and clinical immunology.J Allergy Clin Immunol.2015 Apr;135(4):1031-1043.e6. doi: 10.1016/j.jaci.2014.07.057. Epub 2014 Sep 18.
• BACKGROUND: Anaphylaxis is an acute, potentially lethal, multisystem syndrome resulting from the sudden release of mast cell-derived mediators into the circulation.OBJECTIVES AND METHODS: We report here that a plasma protease cascade, the factor XII-driven contact system, critically contributes to t
• PMID 25240785

• Cerebral visual impairment and intellectual disability caused by PGAP1 variants.

• Bosch DG1, Boonstra FN2, Kinoshita T3, Jhangiani S4, de Ligt J5, Cremers FP5, Lupski JR6, Murakami Y3, de Vries BB7.
• European journal of human genetics : EJHG.Eur J Hum Genet.2015 Mar 25. doi: 10.1038/ejhg.2015.42. [Epub ahead of print]
• Homozygous variants in PGAP1 (post-GPI attachment to proteins 1) have recently been identified in two families with developmental delay, seizures and/or spasticity. PGAP1 is a member of the glycosylphosphatidylinositol anchor biosynthesis and remodeling pathway and defects in this pathway are a subc
• PMID 25804403

Japanese Journal

• Subdural Hematoma in a Patient With Hageman Trait : Case Report

• Neurologia medico-chirurgica 45(12), 640-644, 2005-12-15
• NAID 110002556734

• 血液凝固第XII因子(Hageman 因子)低下患者に対する顎変形症手術の経験

• 有病者歯科医療 = Journal of Japanese Society of Dentistry for Medically Compromised Patient 10(2), 103-106, 2001-12-20
• NAID 10012998950

• 血液凝固第XII因子 (Hageman因子) 低下患者に対する顎変形症手術の経験

• 有病者歯科医療 10(2), 103-106, 2001
• NAID 130004298394

Related Links

• Factor XII (Hageman factor) deficiency: MedlinePlus Medical ...

When you bleed, the body a series of reactions takes place to help the blood clot. This is called the coagulation cascade. Factor XII is a special protein, called a coagulation factor, which helps in this process. Each ...

• Hageman factor deficiency - RightDiagnosis.com

Hageman factor deficiency symptoms, causes, diagnosis, and treatment information for Hageman factor deficiency (Hageman factor deficiency) with alternative diagnoses, full-text book chapters, misdiagnosis, research treatments ...

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★リンクテーブル★

リンク元	「ハーゲマン因子欠乏症」
関連記事	「deficiency」「fact」「factor」「Hageman factor」

「ハーゲマン因子欠乏症」

　　[★]

英

Hageman factor deficiency

関

先天性第XII因子欠乏症

「deficiency」

　　[★]

• n.

• 不足、欠乏、欠失、欠如、欠損、不十分。栄養不足、栄養素欠乏、欠乏症。(遺伝子)(染色体内の)遺伝子欠失
• 欠けているもの、不足している物。不足分。不完全なもの、欠点のあるもの

関

absence, agenesis, dearth, defect, defective, deficient, deficit, delete, deletion, deletional, depletion, deprivation, deprive, lack, miss, missing, morphological defect, paucity, scarce, scarcity, starve

　

「fact」

　　[★]

• n.

• 事実、現状、実際、実態

関

actual、actually、in fact、in practice、indeed、practically

　 　 　 　 　

「factor」

　　[★]

• n.

• 因子、要因、要素、ファクター

関

element、elementary、factorial、parameter

　 　 　 　 　 　 　

「Hageman factor」

　　[★]

関

coagulation factors, factor XII

同

factor XII