Characteristics of alpha-1 antitrypsin variants

PI allele	Protein/cellular consequences	Organs affected
Normal alleles
M (various subtypes)	None	None
X_christchurch	None	None
Deficiency alleles associated with intracellular accumulation
Z	Intracellular accumulation; defective inhibition of neutrophil elastase	Liver, lung
M_malton	Intracellular accumulation	Liver, lung
S_iiyama	Intracellular accumulation	Liver, lung
Deficiency alleles associated with intracellular degradation
M_heerlen	Intracellular degradation	Lung
M_procida	Intracellular degradation	Lung
M_{mineral springs}	Intracellular degradation; defective inhibition of neutrophil elastase	Lung
S	Intracellular degradation	Lung
Null alleles*
QO_{granite falls}	Stop codon; no mRNA or protein	Emphysema
QO_ludwigshafen	mRNA present but abnormal; protein destabilized	Liver, lung
QO_hongkong¹	Frameshift with stop codon; short protein; intracellular accumulation	Early-onset emphysema
QO_{isola di procida}	Deletion; no mRNA; no protein	High risk of emphysema
QO_bolton	Stop codon; no mRNA or protein	High risk emphysema
Dysfunctional alleles
Pittsburg	Substitution	Bleeding diathesis due to change in protein to have antithrombin properties
F	Impaired binding to neutrophil elastase	Normal serum alpha-1 antitrypsin level but impaired anti-elastase functional activity

PI: Protease inhibitor.
* Null alleles have less than 1% of the normal concentration of alpha-1 antitrypsin.

Data adapted from:

DeMeo DL, Silverman EK. Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk. Thorax 2004; 59:259.
Frazier GC1, Siewertsen MA, Hofker MH, et al. A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure. J Clin Invest 1990; 86:1878.
OMIM. https://omim.org/entry/107400 (Accessed on August 18, 2020).

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