Factor XII

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coagulation factor XII
Symbol F12
Entrez 2161
HUGO 3530
OMIM 234000
RefSeq NM_000505
UniProt P00748
Other data
EC number
Locus Chr. 5 q33-qter

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


Hageman factor is a plasma protein now usually known as factor XII. It is an enzyme (EC of the serine protease (or serine endopeptidase) class.


It is part of the coagulation cascade and activates factor XI and prekallikrein.

The coagulation cascade.


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

Role in disease

Hageman factor deficiency is a rare hereditary disorder with a prevalence of about one in a million, although it is a little more common among Asians. Deficiency does not cause excessive hemorrhage as the other coagulation factors make up for the it. It may increase the risk of thrombosis, due to inadequate activation of the fibrinolytic pathway. The deficiency leads to activated partial thromboplastin times (PTT) greater than 200 seconds.

Two missense mutations have been identified in F12, the gene encoding human coagulation factor XII. These mutations are thought to be the cause of a very rare form of hereditary angioedema (HAE), called HAE type III.[1]


Hageman factor was first discovered in 1955 when a routine preoperative blood sample of the 37-year-old railroad brakeman John Hageman 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.[2] Dr. Ratnoff later found that the Hageman factor deficiency is autosomal recessive disorder, when examining several related people which had the deficiency. Paradoxically, pulmonary embolism contributed to Hageman's death after an occupational accident. Since then, case series clinical studies have identified an association of thrombosis and Factor XII deficiency, though the pathophysiology of the relationship is unclear.


  1. Cichon S, Martin L, Hennies HC; et al. (2006). "Increased activity of coagulation factor XII (Hageman factor) causes hereditary angioedema type III". Am. J. Hum. Genet. 79 (6): 1098–104. PMID 17186468. doi:10.1086/509899. 
  2. Ratnoff OD, Margolius A (1955). "Hageman trait: an asymptomatic disorder of blood coagulation". Trans. Assoc. Am. Physicians. 68: 149–54. PMID 13299324. 

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