rs6647

This is a variant in the SERPINA1 gene that changes a valine to an alanine.

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

alpha-1-antitrypsin measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)
Allele A
OR 0.23
p 1.0e-51
N 10,708
Large GWAS
European
Thareja G et al. “Differences and commonalities in the genetic architecture of protein quantitative trait loci in European and Arab populations.” Human Molecular Genetics 32(6):907-916 (2023)
Allele A
OR 0.34
p 6.0e-20
N 2,935
Large GWAS
Greater Middle Eastern (Middle Eastern, North African or Persian)
Surapaneni A et al. “Identification of 969 protein quantitative trait loci in an African American population with kidney disease attributed to hypertension.” Kidney International 102(5):1167-1177 (2022)
Allele A
OR 0.59
p 1.0e-23
N 466
Small GWAS
African American or Afro-Caribbean

large artery stroke

Malik R et al. “Common coding variant in SERPINA1 increases the risk for large artery stroke.” Proceedings of the National Academy of Sciences of the United States of America 114(14):3613-3618 (2017)
Allele G
OR 1.22
p 6.0e-9
N 12,524
Large GWAS
multi-ancestry
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ClinVar annotation

Likely Benign★★★☆
14 submitters5 publications

Alpha-1-antitrypsin deficiency (A1ATD); Inborn genetic diseases; PI M1-ALA213; PI, M1A; not specified

View on ClinVar →
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Research that mentions this SNP (1)

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Genetic diversity from a limited repertoire of mutations on different common allelic backgrounds: α1-antitrypsin deficiency variant Pduarte
ReviewHildesheim J. et al.(1993)· Human Mutation

Alpha-1 Antitrypsin Deficiency (AATD) is caused by over 120 mutations in SERPINA1, with the Z allele (p.Glu342Lys) and S allele (p.Glu264Val) being major pathogenic variants. Large-scale genomic sequencing has revealed >500 rare SERPINA1 variants, many with loss-of-function or gain-of-function effects causing varied clinical manifestations including pulmonary emphysema and hepatic disease. This review synthesizes the SERPINA1 mutation spectrum, their geographic distribution, population history, and pathophysiological mechanisms to guide comprehensive AATD diagnosis beyond common variants.

Traits studied:ANCA-associated vasculitisAlpha-1 Antitrypsin DeficiencyBronchiectasisChronic Obstructive Pulmonary DiseaseEmphysemaHepatic diseaseLiver diseasePanniculitis
PubMedDOIMetascience Observatory

About SERPINA1

The protein encoded by this gene is a serine protease inhibitor belonging to the serpin superfamily whose targets include elastase, plasmin, thrombin, trypsin, chymotrypsin, and plasminogen activator. This protein is produced in the liver, the bone marrow, by lymphocytic and monocytic cells in lymphoid tissue, and by the Paneth cells of the gut. Defects in this gene are associated with chronic obstructive pulmonary disease, emphysema, and chronic liver disease. Several transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Aug 2020]

View all SERPINA1 variants →

Gene information from NCBI Gene. Variant classifications from ClinVar.

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