Gene: SERPINA1

Alternate names for this Gene: A1A|A1AT|AAT|PI|PI1|PRO2275|alpha1AT|nNIF

Gene Summary: The protein encoded by this gene is secreted and is a serine protease inhibitor whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. Defects in this gene can cause emphysema or liver disease. Several transcript variants encoding the same protein have been found for this gene.

Gene is located in Chromosome: 14

Location in Chromosome : 14q32.13

Description of this Gene: serpin family A member 1

Type of Gene: protein-coding

rs121912714 in SERPINA1 gene and Abnormality of the liver PMID 2787118 1989 The deficient alpha-I-antitrypsin phenotype PI P is associated with an A-to-T transversion in exon III of the gene.

PMID 2989709 1985 DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z.

rs28929474 in SERPINA1 gene and Alanine aminotransferase measurement PMID 28887542 2017 Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.

rs28929474 in SERPINA1 gene and Amino acids measurement PMID 27005778 2016 Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.

rs28929474 in SERPINA1 gene and Biliary calculi PMID 30504769 2018 Genome-wide association meta-analysis yields 20 loci associated with gallstone disease.

rs11846959 in SERPINA1 gene and Blood Protein Measurement PMID 29875488 2018 Genomic atlas of the human plasma proteome.

rs28929474 in SERPINA1 gene and Body Height PMID 29782485 2018 Evaluation and application of summary statistic imputation to discover new height-associated loci.

PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

PMID 28552196 2017 Whole-Genome Sequencing Coupled to Imputation Discovers Genetic Signals for Anthropometric Traits.

rs28929474 in SERPINA1 gene and Breast size PMID 27182965 2016 Detection and interpretation of shared genetic influences on 42 human traits.

rs1303 in SERPINA1 gene and Calcification of coronary artery PMID 22916037 2012 Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis.

rs11558261 in SERPINA1 gene and Chronic Obstructive Airway Disease PMID 2227940 1990 Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu).

PMID 2787118 1989 The deficient alpha-I-antitrypsin phenotype PI P is associated with an A-to-T transversion in exon III of the gene.

PMID 2989709 1985 DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z.

PMID 1967187 1990 Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele.

PMID 3262617 1988 "Characterization of the gene and protein of the alpha 1-antitrypsin ""deficiency"" allele Mprocida."

PMID 2606478 1989 Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256----Val); PiMmalton (Phe51----deletion) and PiI (Arg39----Cys).

PMID 2254451 1990 A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure.

PMID 8358043 1993 PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan.

PMID 2786335 1989 In-frame single codon deletion in the Mmalton deficiency allele of alpha 1-antitrypsin.

rs28929474 in SERPINA1 gene and Forced expiratory volume function PMID 30068317 2018 Genome-wide association study of lung function and clinical implication in heavy smokers.

PMID 26634245 2015 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.

rs28929474 in SERPINA1 gene and Glucagon measurement PMID 29093273 2017 Genetic determinants of circulating GIP and GLP-1 concentrations.

rs28929474 in SERPINA1 gene and Glucose tolerance test PMID 29093273 2017 Genetic determinants of circulating GIP and GLP-1 concentrations.

rs28929474 in SERPINA1 gene and Lean body mass PMID 30593698 2019 Genomics of body fat percentage may contribute to sex bias in anorexia nervosa.

rs17580 in SERPINA1 gene and Low density lipoprotein cholesterol measurement PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 29083408 2017 Exome-wide association study of plasma lipids in >300,000 individuals.

rs28929474 in SERPINA1 gene and Movement Disorders PMID 26310624 2015 Impaired hepcidin expression in alpha-1-antitrypsin deficiency associated with iron overload and progressive liver disease.

PMID 9041988 1997 Baseline characteristics of enrollees in the National Heart, Lung and Blood Institute Registry of alpha 1-antitrypsin deficiency. Alpha 1-Antitrypsin Deficiency Registry Study Group.

PMID 15115878 2004 Alpha 1-antitrypsin deficiency. 3: Clinical manifestations and natural history.

PMID 6306478 1983 alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.

PMID 18682522 2008 Clinical course and prognosis of never-smokers with severe alpha-1-antitrypsin deficiency (PiZZ).

PMID 23632999 2013 α1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population.

rs17580 in SERPINA1 gene and Platelet Count measurement PMID 27863252 2016 The Allelic Landscape of Human Blood Cell Trait Variation and Links to Common Complex Disease.

rs28929474 in SERPINA1 gene and Protein measurement PMID 27005778 2016 Genome-wide study for circulating metabolites identifies 62 loci and reveals novel systemic effects of LPA.

rs11558261 in SERPINA1 gene and Pulmonary Emphysema PMID 2227940 1990 Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu).

PMID 2787118 1989 The deficient alpha-I-antitrypsin phenotype PI P is associated with an A-to-T transversion in exon III of the gene.

PMID 2989709 1985 DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z.

PMID 1967187 1990 Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele.

PMID 3262617 1988 "Characterization of the gene and protein of the alpha 1-antitrypsin ""deficiency"" allele Mprocida."

PMID 2606478 1989 Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256----Val); PiMmalton (Phe51----deletion) and PiI (Arg39----Cys).

PMID 2254451 1990 A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure.

PMID 8358043 1993 PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan.

PMID 2786335 1989 In-frame single codon deletion in the Mmalton deficiency allele of alpha 1-antitrypsin.

rs28929474 in SERPINA1 gene and Serum Alanine Aminotransferase Measurement PMID 28887542 2017 Genome-wide analysis of health-related biomarkers in the UK Household Longitudinal Study reveals novel associations.

rs17580 in SERPINA1 gene and Serum total cholesterol measurement PMID 30275531 2018 Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.

PMID 29507422 2018 A large electronic-health-record-based genome-wide study of serum lipids.

rs28929474 in SERPINA1 gene and Smoking PMID 30068317 2018 Genome-wide association study of lung function and clinical implication in heavy smokers.

rs28929474 in SERPINA1 gene and Smoking Behaviors PMID 30068317 2018 Genome-wide association study of lung function and clinical implication in heavy smokers.

rs28929474 in SERPINA1 gene and Systolic Pressure PMID 30595370 2019 Leveraging Polygenic Functional Enrichment to Improve GWAS Power.

rs1057519610 in SERPINA1 gene and alpha 1-Antitrypsin Deficiency PMID 14985567 2004 Alpha1-antitrypsin deficiency. 2: genetic aspects of alpha(1)-antitrypsin deficiency: phenotypes and genetic modifiers of emphysema risk.

PMID 2227940 1990 Molecular characterisation of two alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) Null(Newport) (Gly115----Ser) and (Pi) Z Wrexham (Ser-19----Leu).

PMID 15744045 2005 Prevalence and phenotype of subjects carrying rare variants in the Italian registry for alpha1-antitrypsin deficiency.

PMID 14767073 2004 Retarded protein folding of deficient human alpha 1-antitrypsin D256V and L41P variants.

PMID 17906067 2007 "Genotypes and serum concentrations of human alpha-1-antitrypsin ""P"" protein variants in a clinical population."

PMID 21474916 2011 Population genetic screening for alpha1-antitrypsin deficiency in a high-prevalence area.

PMID 15949707 2005 Comparison of the properties of rare variants of alpha1-proteinase inhibitor expressed in COS-1 cells and assessment of their potential as risk factors in human disease.

PMID 2787118 1989 The deficient alpha-I-antitrypsin phenotype PI P is associated with an A-to-T transversion in exon III of the gene.

PMID 2240842 1990 Molecular analysis of the heterogeneity among the P-family of alpha-1-antitrypsin alleles.

PMID 9635295 1998 Alpha 1-antitrypsin nonsense mutation associated with a retained truncated protein and reduced mRNA.

PMID 8970361 1996 Clinical features of individuals with PI*SZ phenotype of alpha 1-antitrypsin deficiency. alpha 1-Antitrypsin Deficiency Registry Study Group.

PMID 25454901 2015 The PiZ (rs28929474) and PiS (rs17580) variants are believed to cause severe AAT deficiency and are linked to a high risk of developing COPD.

PMID 22975760 2013 An empirical estimate of carrier frequencies for 400+ causal Mendelian variants: results from an ethnically diverse clinical sample of 23,453 individuals.

PMID 22426792 2012 Serum levels and genotype distribution of α1-antitrypsin in the general population.

PMID 2567291 1989 Serum alpha 1-antitrypsin deficiency associated with the common S-type (Glu264----Val) mutation results from intracellular degradation of alpha 1-antitrypsin prior to secretion.

PMID 20981092 2010 A map of human genome variation from population-scale sequencing.

PMID 26672964 2015 Prevalence of PI*Z and PI*S alleles of alpha-1-antitrypsin deficiency in Finland.

PMID 23632999 2013 α1-Antitrypsin phenotypes and associated serum protein concentrations in a large clinical population.

PMID 1889260 1991 Use of a highly purified alpha 1-antitrypsin standard to establish ranges for the common normal and deficient alpha 1-antitrypsin phenotypes.

PMID 26141072 2015 PiSZ alpha-1 antitrypsin deficiency (AATD): pulmonary phenotype and prognosis relative to PiZZ AATD and PiMM COPD.

PMID 26831755 2016 A study of common Mendelian disease carriers across ageing British cohorts: meta-analyses reveal heterozygosity for alpha 1-antitrypsin deficiency increases respiratory capacity and height.

PMID 22933512 2012 Prevalence of α1-antitrypsin deficiency alleles PI*S and PI*Z worldwide and effective screening for each of the five phenotypic classes PI*MS, PI*MZ, PI*SS, PI*SZ, and PI*ZZ: a comprehensive review.

PMID 24055113 2013 Actionable, pathogenic incidental findings in 1,000 participants' exomes.

PMID 15978931 2005 Alpha1-antitrypsin deficiency.

PMID 25391508 2014 Diagnosis of alpha-1 antitrypsin deficiency: modalities, indications and diagnosis strategy.

PMID 27296815 2016 Alpha-1-antitrypsin (SERPINA1) mutation spectrum: Three novel variants and haplotype characterization of rare deficiency alleles identified in Portugal.

PMID 2784123 1989 A Pro----Leu substitution in codon 369 of the alpha-1-antitrypsin deficiency variant PI MHeerlen.

PMID 26321041 2015 SERPINA1 Full-Gene Sequencing Identifies Rare Mutations Not Detected in Targeted Mutation Analysis.

PMID 18024524 2008 Inherited chronic obstructive pulmonary disease: new selective-sequencing workup for alpha1-antitrypsin deficiency identifies 2 previously unidentified null alleles.

PMID 10234508 1999 Molecular characterisation of the defective alpha 1-antitrypsin alleles PI Mwurzburg (Pro369Ser), Mheerlen (Pro369Leu), and Q0lisbon (Thr68Ile).

PMID 3040726 1987 alpha 1-Antitrypsin nullGranite Falls, a nonexpressing alpha 1-antitrypsin gene associated with a frameshift to stop mutation in a coding exon.

PMID 2481421 1989 Characterization of the intracellular mechanism causing the alpha-1-antitrypsin Nullgranite falls deficiency state.

PMID 18353624 2008 Alpha-1 antitrypsin Null mutations and severity of emphysema.

PMID 2642408 1989 The alpha 1-antitrypsin gene and its mutations. Clinical consequences and strategies for therapy.

PMID 7980208 1994 Absence of alpha-1-antitrypsin (Pi Null Bellingham) and the early onset of emphysema.

PMID 3257351 1988 Emphysema associated with complete absence of alpha 1- antitrypsin in serum and the homozygous inheritance [corrected] of a stop codon in an alpha 1-antitrypsin-coding exon.

PMID 19444872 2009 Single nucleotide polymorphism-mediated translational suppression of endoplasmic reticulum mannosidase I modifies the onset of end-stage liver disease in alpha1-antitrypsin deficiency.

PMID 22971141 2012 Alpha-1-antitrypsin deficiency in Serbian adults with lung diseases.

PMID 9195389 1997 Review: alpha 1-antitrypsin deficiency associated liver disease.

PMID 21228398 2011 Carrier testing for severe childhood recessive diseases by next-generation sequencing.

PMID 21067581 2010 Polymorphism of SERPINE2 gene is associated with pulmonary emphysema in consecutive autopsy cases.

PMID 6306478 1983 alpha 1-antitrypsin deficiency detection by direct analysis of the mutation in the gene.

PMID 15454649 2004 Chronic obstructive pulmonary disease in alpha1-antitrypsin PI MZ heterozygotes: a meta-analysis.

PMID 3264419 1988 Neonatal hepatitis induced by alpha 1-antitrypsin: a transgenic mouse model.

PMID 19738092 2009 Genetic modifiers of liver disease in cystic fibrosis.

PMID 3500183 1987 Z-type alpha 1-antitrypsin is less competent than M1-type alpha 1-antitrypsin as an inhibitor of neutrophil elastase.

PMID 7045697 1982 Structure and variation of human alpha 1-antitrypsin.

PMID 1608473 1992 The mechanism of Z alpha 1-antitrypsin accumulation in the liver.

PMID 3484754 1986 "Evaluation of ""at risk"" alpha 1-antitrypsin genotype SZ with synthetic oligonucleotide gene probes."

PMID 22912729 2012 SERPINA1 PiZ and PiS heterozygotes and lung function decline in the SAPALDIA cohort.

PMID 2700304 1989 Alpha-1-antitrypsin deficiency: accumulation or degradation of mutant variants within the hepatic endoplasmic reticulum.

PMID 22735536 2012 Conformational properties of the disease-causing Z variant of α1-antitrypsin revealed by theory and experiment.

PMID 26987331 2016 Frequency of Rare Alpha-1 Antitrypsin Variants in Polish Patients with Chronic Respiratory Disorders.

PMID 24428606 2014 Clarification of the risk of chronic obstructive pulmonary disease in α1-antitrypsin deficiency PiMZ heterozygotes.

PMID 23858502 2013 A patient with the rare alpha-1-antitrypsin variant (Z)bristol in compound heterozygosity with the Z mutation.

PMID 9569237 1998 Lung polymers in Z alpha1-antitrypsin deficiency-related emphysema.

PMID 2904702 1988 Repair of the secretion defect in the Z form of alpha 1-antitrypsin by addition of a second mutation.

PMID 24518491 2014 Pi*Z heterozygous alpha-1 antitrypsin states accelerate parenchymal but not biliary cirrhosis.

PMID 18515255 2008 SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations.

PMID 2989709 1985 DNA restriction fragments associated with alpha 1-antitrypsin indicate a single origin for deficiency allele PI Z.

PMID 25181470 2014 The Z mutation alters the global structural dynamics of α1-antitrypsin.

PMID 23837941 2014 Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes.

PMID 12034572 2002 Polymers of alpha(1)-antitrypsin are chemotactic for human neutrophils: a new paradigm for the pathogenesis of emphysema.

PMID 14522813 2003 American Thoracic Society/European Respiratory Society statement: standards for the diagnosis and management of individuals with alpha-1 antitrypsin deficiency.

PMID 2339709 1990 Sequence data of the rare deficient alpha 1-antitrypsin variant PI Zaugsburg.

PMID 26304913 2015 Fibrinogen and α1-antitrypsin in COPD exacerbations.

PMID 19083091 2009 Analysis of the alpha-1-antitrypsin deficient alleles M3S, MZ, and ZZ by biochemical and molecular methods: a family study.

PMID 21637600 2010 Alpha-1 antitrypsin gene polymorphism in Chronic Obstructive Pulmonary Disease (COPD).

PMID 26243289 2015 Quantitation of circulating wild-type alpha-1-antitrypsin in heterozygous carriers of the S and Z deficiency alleles.

PMID 24328305 2014 Increased outer arm and core fucose residues on the N-glycans of mutated alpha-1 antitrypsin protein from alpha-1 antitrypsin deficient individuals.

PMID 18340647 2008 Population-based case-control study of alpha 1-antitrypsin and SLC11A1 in Crohn's disease and ulcerative colitis.

PMID 24082139 2013 Personalized genomic disease risk of volunteers.

PMID 21960536 2012 A review of α1-antitrypsin deficiency.

PMID 1967187 1990 Molecular basis of alpha 1-antitrypsin deficiency and emphysema associated with the alpha 1-antitrypsin Mmineral springs allele.

PMID 3262617 1988 "Characterization of the gene and protein of the alpha 1-antitrypsin ""deficiency"" allele Mprocida."

PMID 24713750 2014 Challenging identification of a novel PiISF and the rare PiMmaltonZ α1-antitrypsin deficiency variants in two patients.

PMID 21752289 2011 The prevalence of alpha-1 antitrypsin deficiency in Ireland.

PMID 2606478 1989 Molecular characterisation of three alpha-1-antitrypsin deficiency variants: proteinase inhibitor (Pi) nullcardiff (Asp256----Val); PiMmalton (Phe51----deletion) and PiI (Arg39----Cys).

PMID 22912357 2012 Reference and interpretive ranges for α(1)-antitrypsin quantitation by phenotype in adult and pediatric populations.

PMID 10194472 1999 Heteropolymerization of S, I, and Z alpha1-antitrypsin and liver cirrhosis.

PMID 3496639 1987 Study of familial alpha-1-proteinase inhibitor deficiency including a rare proteinase inhibitor phenotype (IZ). I. Alpha-1-phenotyping and clinical investigations.

PMID 1504305 1992 Molecular characterization of the P and I variants of alpha 1-antitrypsin.

PMID 17964515 2007 Laboratory diagnosis of alpha1-antitrypsin deficiency.

PMID 2254451 1990 A null deficiency allele of alpha 1-antitrypsin, QOludwigshafen, with altered tertiary structure.

PMID 1905728 1991 Siiyama (serine 53 (TCC) to phenylalanine 53 (TTC)). A new alpha 1-antitrypsin-deficient variant with mutation on a predicted conserved residue of the serpin backbone.

PMID 15486938 2004 Differential detection of PAS-positive inclusions formed by the Z, Siiyama, and Mmalton variants of alpha1-antitrypsin.

PMID 8520784 1995 Alpha 1-antitrypsin-deficient variant Siiyama (Ser53[TCC] to Phe53[TTC]) is prevalent in Japan. Status of alpha 1-antitrypsin deficiency in Japan.

PMID 8340361 1993 Alpha 1-antitrypsin Siiyama (Ser53-->Phe). Further evidence for intracellular loop-sheet polymerization.

PMID 22016686 2011 Identification of compound heterozygous mutation in a Korean patient with alpha 1-antitrypsin deficiency.

PMID 8358043 1993 PI*S(iiyama), a deficiency gene of alpha 1-antitrypsin: evidence for the occurrence in western Japan.

PMID 19437508 2009 Molecular characterization of the new defective P(brescia) alpha1-antitrypsin allele.

PMID 11214903 2001 Patterns of haplotype diversity within the serpin gene cluster at 14q32.1: insights into the natural history of the alpha1-antitrypsin polymorphism.

PMID 22723858 2012 Three new alpha1-antitrypsin deficiency variants help to define a C-terminal region regulating conformational change and polymerization.

PMID 19654085 2010 [Biochemical and molecular diagnosis of alpha 1 antitrypsin deficiency in a Tunisian family].

PMID 11474657 2001 Association between the defective Pro369Ser mutation and in vivo intrahepatic 1-antitrypsin accumulation.

PMID 8364536 1993 Characterization of a human alpha 1-antitrypsin null allele involving aberrant mRNA splicing.

PMID 10954248 2000 Molecular mechanisms of alpha1-antitrypsin null alleles.

PMID 2539391 1989 Alpha 1-antitrypsin deficiency caused by the alpha 1-antitrypsin Nullmattawa gene. An insertion mutation rendering the alpha 1-antitrypsin gene incapable of producing alpha 1-antitrypsin.

PMID 26604020 2016 [Alpha-1 antitrypsin deficiency caused by Null mutation].

PMID 1730596 1992 Secretion of alpha-1-proteinase inhibitor requires an almost full length molecule.

PMID 9070606 1997 alpha1-antitrypsin gene mutation hot spot associated with the formation of a retained and degraded null variant [corrected; erratum to be published].

PMID 7977369 1994 Identification and DNA sequence analysis of 15 new alpha 1-antitrypsin variants, including two PI*Q0 alleles and one deficient PI*M allele.

PMID 11334395 2001 Compound heterozygosity for alpha-1-antitrypsin (S(iiyama) and QO(clayton)) in an Oriental patient.

PMID 24183282 2013 Alpha-1-antitrypsin deficiency associated with the Mattawa variant.

PMID 24969923 2014 Is an integrative laboratory algorithm more effective in detecting alpha-1-antitrypsin deficiency in patients with premature chronic obstructive pulmonary disease than AAT concentration based screening approach?

PMID 22291048 2012 Rare alpha-1-antitrypsin variants: are they really so rare?

PMID 3491442 1986 Alpha 1 antitrypsin deficiency due to MMaltonZ phenotype: case report and family study.

PMID 2788166 1989 Molecular basis of the liver and lung disease associated with the alpha 1-antitrypsin deficiency allele Mmalton.

PMID 6600898 1983 Pulmonary function associated with the Mmalton deficient variant of alpha 1-antitrypsin.

PMID 2786335 1989 In-frame single codon deletion in the Mmalton deficiency allele of alpha 1-antitrypsin.

PMID 21457231 2012 Severe α-1 antitrypsin deficiency caused by Q0(Ourém) allele: clinical features, haplotype characterization and history.

PMID 12220457 2002 alpha1-Antitrypsin null alleles: evidence for the recurrence of the L353fsX376 mutation and a novel G-->A transition in position +1 of intron IC affecting normal mRNA splicing.

PMID 25425243 2014 Identification and characterisation of eight novel SERPINA1 Null mutations.

rs28929474 in SERPINA1 gene and response to bronchodilator PMID 26634245 2015 A genome-wide association study identifies risk loci for spirometric measures among smokers of European and African ancestry.