What you carry at this position in your DNA and what research says about it.
Alpha-1 Antitrypsin Deficiency: 10/10 evidence, 73 publications.
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Sample genotype (not yours): C/C
Typical Lung and Liver Disease Risk
Two copies of the normal C allele ensure typical production and secretion of the protective alpha-1 antitrypsin protein. This genotype maintains standard defense mechanisms against inflammatory lung damage.
What this genotype means: Typical lung function; Standard liver enzyme levels; Typical risk of emphysema.
Sample genotype (not yours): C/T
Carrier for Alpha-1 Antitrypsin Deficiency
Carrying one copy of the Z allele reduces circulating levels of the protective protein. This increases susceptibility to lung and liver complications, especially in smokers.
What this genotype means: Reduced circulating alpha-1 antitrypsin; Elevated risk of lung irritation from smoke; Slightly increased risk of liver stress.
Sample genotype (not yours): T/T
Severe Alpha-1 Antitrypsin Deficiency Risk
Two copies of the Z allele cause severe alpha-1 antitrypsin deficiency. This dramatically increases the risk of early-onset emphysema and progressive liver disease.
What this genotype means: Severe lack of circulating protective protein; High risk of early-onset emphysema; High risk of progressive liver disease.
Gene function and biological role
Gene Function: The SERPINA1 gene encodes alpha-1 antitrypsin, a protective protein primarily synthesized in the liver and secreted into the bloodstream [1]. Its main physiological role is to safeguard delicate lung tissues from being degraded by inflammatory enzymes like neutrophil elastase [1] [2]. When this protein is deficient or structurally altered, the lungs lose their primary defense mechanism, leading to progressive tissue breakdown [2]. Additionally, abnormal accumulation of the protein within liver cells can trigger localized inflammation and cellular damage [1] [3].
Variant Impact: This missense variant, widely known as the PI*Z or Z allele, alters the amino acid at position 366 from glutamate to lysine [2]. This single change causes the alpha-1 antitrypsin protein to misfold and polymerize, trapping it inside liver cells instead of allowing its release into circulation [2] [4]. Consequently, blood levels of this protective protein drop severely, leaving the lungs highly vulnerable to damage [4]. It represents the most common genetic cause of severe alpha-1 antitrypsin deficiency [4] [1].
Key Insight: While the Z allele is notorious for causing severe lung and liver disease when inherited from both parents, carriers of a single copy actually show a slight evolutionary trade-off, including lower blood pressure and a reduced risk of osteoarthritis.
Location: SERPINA1. Chromosome 14 · 14q32.13 · 94.4 Mb
Estimated prevalence by population
Global 97.6%; European 95.9%; African 99.5%; East Asian 100.0%; South Asian 99.9%; Americas 98.8%; Ashkenazi 98.1%; Finnish 96.6%; Middle Eastern 100.0%; Amish 98.5%.
Estimated CC genotype frequency.
Global 2.4%; European 4.0%; African 0.5%; East Asian 0.0%; South Asian 0.1%; Americas 1.2%; Ashkenazi 1.9%; Finnish 3.4%; Middle Eastern 0.0%; Amish 1.5%.
Estimated CT genotype frequency.
Global < 0.1%; European < 0.1%; African < 0.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi < 0.1%; Finnish < 0.1%; Middle Eastern 0.0%; Amish < 0.1%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Organ Systems
Respiratory Health
Alpha-1 Antitrypsin Deficiency. Evidence: 5/10. Source: PMID 20301692. Typical Risk.
Liver Function & Disease
Liver Cirrhosis. Evidence: 10/10. Source: PMID 33310085. Typical Risk.
Digestive & Gut Disorders
Gallstones. Evidence: 10/10. Source: PMID 30504769. Typical Risk.
Bone, Joint & Connective Tissue Health
Osteoarthritis. Evidence: 8/10. Source: PMID 34450027. Typical Risk.
Endocrine & Reproductive
Hormone Levels & Endocrine Regulation
Testosterone Levels. Evidence: 10/10. Source: PMID 32042192. Typical Levels.
Cardiovascular & Metabolic
Hypertension
Systolic Blood Pressure. Evidence: 10/10. Source: PMID 30595370. Typical.
Showing effects for C/T genotype
Alpha-1 Antitrypsin Deficiency. Evidence: 5/10. Source: PMID 20301692. Elevated COPD Risk.
Liver Cirrhosis. Evidence: 10/10. Source: PMID 33310085. Slightly Increased.
Gallstones. Evidence: 10/10. Source: PMID 30504769. Increased Risk.
Osteoarthritis. Evidence: 8/10. Source: PMID 34450027. Reduced Risk.
Testosterone Levels. Evidence: 10/10. Source: PMID 32042192. Slightly Higher.
Systolic Blood Pressure. Evidence: 10/10. Source: PMID 30595370. Slightly Lower.
Showing effects for T/T genotype
Alpha-1 Antitrypsin Deficiency. Evidence: 5/10. Source: PMID 20301692. Very High Risk.
Liver Cirrhosis. Evidence: 10/10. Source: PMID 33310085. Highly Increased.
Gallstones. Evidence: 10/10. Source: PMID 30504769. Highly Increased.
Osteoarthritis. Evidence: 8/10. Source: PMID 34450027. Lowest Risk.
Testosterone Levels. Evidence: 10/10. Source: PMID 32042192. Higher Levels.
Systolic Blood Pressure. Evidence: 10/10. Source: PMID 30595370. Lower.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Standard levels of circulating alpha-1 antitrypsin are maintained by this common genotype, providing robust protection for the lungs [1]. Because the protein is successfully secreted from the liver, there is no abnormal accumulation or associated liver stress [1] [2]. The risk of developing emphysema, chronic obstructive pulmonary disease (COPD), or liver cirrhosis remains at the baseline population level [2] [3]. However, this genotype is associated with a slightly higher baseline risk of osteoarthritis and slightly higher blood pressure compared to carriers of the variant allele [4] [5]. Maintaining a healthy lifestyle, avoiding smoking, and minimizing alcohol intake are still recommended to preserve long-term organ health.
Typical lung function; Standard liver enzyme levels; Typical risk of emphysema.
Sample genotype: CT (Heterozygous)
Circulating levels of alpha-1 antitrypsin are typically reduced to about 50% to 60% of normal in those with this carrier status [1]. While many carriers remain healthy throughout life, there is an elevated risk of developing chronic obstructive pulmonary disease (COPD), particularly if exposed to tobacco smoke [2]. Misfolded proteins can also accumulate in liver cells, leading to mild liver stress and a higher risk of gallstones or cirrhosis [3] [4]. Interestingly, large-scale genetic studies show carriers have slightly lower blood pressure and a reduced risk of osteoarthritis [5] [6]. Avoiding smoking and limiting alcohol consumption are highly critical preventative measures for individuals with this genetic profile.
Reduced circulating alpha-1 antitrypsin; Elevated risk of lung irritation from smoke; Slightly increased risk of liver stress.
Sample genotype: TT (Homozygous)
Severe deficiency of the protective alpha-1 antitrypsin protein occurs with this genotype, as circulating levels drop to approximately 15% of normal [1]. The misfolded proteins polymerize and become trapped inside liver cells, causing direct hepatic injury and significantly raising the risk of cirrhosis [1] [2]. Without adequate protein in the bloodstream, the lungs are left entirely unprotected against destructive enzymes, leading to a very high risk of early-onset emphysema and COPD [3]. Smoking is exceptionally dangerous for individuals with this profile and accelerates lung damage dramatically [3]. Regular medical monitoring of both lung and liver function is highly recommended to manage risks proactively.
Severe lack of circulating protective protein; High risk of early-onset emphysema; High risk of progressive liver disease.
Variants with shared genetic architecture
rs112635299 · SERPINA1 Gene · Chr 14 · Lung and Liver Disease Risk
rs17580 · SERPINA1 Gene · Chr 14 · Lung Health and COPD
rs1303 · SERPINA1 Gene · Chr 14 · Lung Disease Risk
Alpha-1 Antitrypsin Deficiency.
The Z mutation alters the global structural dynamics of α1-antitrypsin.
Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model.
Serum levels and genotype distribution of α1-antitrypsin in the general population.
SERPINA1 and HSD17B13 Gene Variants in Patients with Liver Fibrosis and Cirrhosis.
Translational genomics of osteoarthritis in 1,962,069 individuals.
A Genomics England haplotype reference panel and imputation of UK Biobank.
Content updated August 2026.
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