What you carry at this position in your DNA and what research says about it.
Blood Clot Risk: 10/10 evidence, 19 publications.
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Sample genotype (not yours): T/T
Lower Risk of Blood Clots
Standard blood clotting times help protect against abnormal clots. This genotype is associated with typical levels of clotting factors and a lower risk of thrombosis.
What this genotype means: Typical blood clotting speed; Lower risk of deep vein thrombosis; Standard factor XI levels.
Sample genotype (not yours): C/C
Higher Risk of Blood Clots
Two copies of the variant allele significantly accelerate blood clotting. This genotype is linked to the highest risk of venous thrombosis and ischemic stroke.
What this genotype means: Fastest blood clotting speed; Highest risk of deep vein thrombosis; Significantly elevated risk of blood clots when using hormonal contraceptives.
Sample genotype (not yours): T/C
Moderately Increased Blood Clot Risk
Carrying one copy of the variant allele slightly accelerates blood clotting. This increases the risk of venous blood clots and ischemic stroke, especially when combined with other risk factors.
What this genotype means: Faster blood clotting speed; Moderately elevated risk of deep vein thrombosis; Elevated risk of blood clots when using hormonal contraceptives.
Gene function and biological role
Gene Function: The KNG1 gene provides instructions for making kininogen 1, a protein that plays a critical role in the blood coagulation cascade and inflammatory response [1]. Kininogen is cleaved to produce high-molecular-weight kininogen (HK) and low-molecular-weight kininogen (LK) [1]. High-molecular-weight kininogen acts as an essential cofactor in the contact activation pathway of blood clotting, helping to initiate the process alongside factor XII and prekallikrein [2]. It also serves as a precursor to bradykinin, a peptide that dilates blood vessels and regulates blood pressure [2]. Genetic variations in this gene can alter the stability or levels of these proteins, directly influencing how quickly blood clots form in the body [3].
Variant Impact: The rs710446 variant is a missense mutation in the KNG1 gene that changes the amino acid at position 581 from isoleucine to threonine (p.Ile581Thr) [3]. This specific amino acid substitution occurs in the light chain of high-molecular-weight kininogen, a region critical for its binding and cofactor activity [3]. By altering the protein structure, this change increases the levels of circulating coagulation factor XI and accelerates the blood clotting cascade [2]. Consequently, this molecular shift shortens the activated partial thromboplastin time (aPTT), leading to a state of hypercoagulability [1]. These altered dynamics directly elevate the susceptibility to abnormal blood clots in the veins and brain [4].
Key Insight: A single amino acid change in kininogen 1 can significantly speed up blood clotting by raising the levels of an entirely different clotting factor, factor XI.
Location: KNG1. Chromosome 3 · 3q27.3 · 186.7 Mb
Estimated prevalence by population
Global 32.0%; European 34.6%; African 23.3%; East Asian 49.8%; South Asian 41.0%; Americas 30.4%; Ashkenazi 23.4%; Finnish 40.0%; Middle Eastern 25.3%; Amish 55.5%.
Estimated TT genotype frequency.
Global 48.5%; European 48.5%; African 49.9%; East Asian 41.5%; South Asian 46.1%; Americas 49.5%; Ashkenazi 49.9%; Finnish 46.5%; Middle Eastern 50.0%; Amish 38.0%.
Estimated TC genotype frequency.
Global 19.5%; European 17.0%; African 26.7%; East Asian 8.6%; South Asian 13.0%; Americas 20.1%; Ashkenazi 26.6%; Finnish 13.5%; Middle Eastern 24.7%; Amish 6.5%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cardiovascular & Metabolic
Coagulation & Clotting
Blood Clot Risk. Evidence: 10/10. Source: PMID 26908601. Lower Risk.
Blood Clotting Speed. Evidence: 8/10. Source: PMID 20303064. Slower Clotting.
Factor XI Levels. Evidence: 10/10. Source: PMID 28053049. Lower Levels.
Contraceptive Clot Risk. Evidence: 5/10. Source: PMID 28750087. Typical Risk.
Stroke
Ischemic Stroke. Evidence: 10/10. Source: PMID 26159646. Lower Risk.
Showing effects for C/C genotype
Blood Clot Risk. Evidence: 10/10. Source: PMID 26908601. Highest Risk.
Blood Clotting Speed. Evidence: 8/10. Source: PMID 20303064. Fastest Clotting.
Factor XI Levels. Evidence: 10/10. Source: PMID 28053049. Highest Levels.
Contraceptive Clot Risk. Evidence: 5/10. Source: PMID 28750087. Highest Risk.
Ischemic Stroke. Evidence: 10/10. Source: PMID 26159646. Highest Risk.
Showing effects for T/C genotype
Blood Clot Risk. Evidence: 10/10. Source: PMID 26908601. Increased Risk.
Blood Clotting Speed. Evidence: 8/10. Source: PMID 20303064. Faster Clotting.
Factor XI Levels. Evidence: 10/10. Source: PMID 28053049. Higher Levels.
Contraceptive Clot Risk. Evidence: 5/10. Source: PMID 28750087. Increased Risk.
Ischemic Stroke. Evidence: 10/10. Source: PMID 26159646. Increased Risk.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Production of standard kininogen 1 proteins with isoleucine at position 581 is maintained by the presence of two reference T alleles [1]. This molecular configuration maintains typical activated partial thromboplastin times, meaning the blood clots at a normal, healthy rate [2]. Because clotting factors like factor XI remain at baseline levels, there is no genetically driven hypercoagulability [3]. Clinical studies show that this baseline state is associated with a significantly lower risk of deep vein thrombosis and pulmonary embolism compared to carrying the variant allele [4]. Furthermore, the risk of ischemic stroke remains at the typical population baseline [4]. This protective profile also extends to situations of hormonal contraceptive use, where the risk of developing a venous clot is not elevated by this genetic factor [5].
Typical blood clotting speed; Lower risk of deep vein thrombosis; Standard factor XI levels.
Sample genotype: CC (Homozygous)
Inheritance of two copies of the C variant allele means all kininogen 1 proteins produced contain threonine instead of isoleucine at position 581 [1]. This complete structural shift maximizes the efficiency of the contact activation pathway, resulting in the highest levels of factor XI [2]. Consequently, the activated partial thromboplastin time is significantly shortened, creating a pronounced hypercoagulable state [3]. Clinical evidence demonstrates that this genotype carries the highest genetic risk for deep vein thrombosis and pulmonary embolism at this locus [4]. Additionally, the risk of ischemic stroke is elevated due to the persistent tendency of the blood to clot too quickly [4]. The risk of venous thromboembolism is further magnified if combined hormonal contraceptives are used, making alternative contraceptive methods a relevant consideration [5].
Fastest blood clotting speed; Highest risk of deep vein thrombosis; Significantly elevated risk of blood clots when using hormonal contraceptives.
Sample genotype: TC (Heterozygous)
Presence of a single C variant allele introduces a structural change in a portion of the kininogen 1 proteins, replacing isoleucine with threonine [1]. This alteration enhances the activity of the contact activation pathway, leading to higher circulating levels of coagulation factor XI [2]. As a result, the activated partial thromboplastin time is shortened, indicating that blood clots form more rapidly than typical [3]. Epidemiological data links this intermediate state to a moderately elevated risk of venous thromboembolism, deep vein thrombosis, and pulmonary embolism [4]. There is also a corresponding increase in the risk of ischemic stroke due to the heightened clotting tendency [4]. Furthermore, using combined hormonal contraceptives can interact with this genetic predisposition, further compounding the risk of developing a venous blood clot [5].
Faster blood clotting speed; Moderately elevated risk of deep vein thrombosis; Elevated risk of blood clots when using hormonal contraceptives.
Variants with shared genetic architecture
rs2304456 · KNG1 Gene · Chr 3 · Kininogen-1 Protein Levels
rs5030062 · KNG1 Gene · Chr 3 · Stroke and Blood Clot Risk
rs10886430 · GRK5 Gene · Chr 10 · Blood Clot Risk
KNG1 Ile581Thr and susceptibility to venous thrombosis.
Risk prediction of developing venous thrombosis in combined oral contraceptive users.
Content updated August 2026.
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