SERPINA1 Gene

The SERPINA1 gene (SERPINA1 stands for "Serine/or Cysteine - Proteinase Inhibitor, Clade A /Alpha-1 Antiproteinase, Antitrypsin Member 1") is a protein-coding gene located on chromosome 14q32.13. 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. Inhibitor of serine proteases. Several transcript variants encoding the same protein have been found for this gene.

The serine protease inhibitor SERPINA1 is produced in the liver, in the bone marrow, by lymphocytic and monocytic cells in the lymphoid tissue and by the Paneth cells of the intestine. The main target of serine protease inhibitor A1 is elastase. Its main physiological function is to protect the lower respiratory tract from proteolytic destruction by human leukocyte elastase. The enzyme also has a moderate affinity for plasmin and thrombin. The aberrant form inhibits insulin-induced NO synthesis in platelets, shortens clotting time and has proteolytic activity towards insulin and plasmin.

Diseases associated with SERPINA1 include alpha-1 antitrypsin deficiency and hemorrhagic disease due to an alpha-1 antitrypsin Pittsburgh mutation.

Furthermore, mutations in SERPINA3 have been described as predisposing risk factors for both AOID (adult-onset immunodeficiency syndrome) and GPP(generalized pustular psoriasis). Kantaputra P et al. (2021) reported on two unrelated patients with AOID and pustulosis and with GPP. In both patients, the same heterozygous variant c.718G>A (p.Val240Met) was detected in SERPINA1. It can be assumed that mutants in SERPINA1, SERPINA3 and possibly also in other members of the SERPIN family may be associated with the etiology of GPP and AOID.

Vulvar squamous cell carcinomas: Overexpression of serpin A1 was detected in 88% of cases of vulvar squamous cell carcinomas, regardless of their etiology. Tumor cell-specific overexpression of serpin A1 is a potential biomarker for these carcinoma species (Lagerstedt M et al. 2019).

1. Kantaputra P et al (2021) SERPINA1, generalized pustular psoriasis, and adult-onset immunodeficiency. J Dermatol 48:1597-1601.
2. Lagerstedt M et al (2019) Tumor cell-specific Serpin A1 expression in vulvar squamous cell carcinoma. Arch Gynecol Obstet 299:1345-1351.