ClinGen Dosage Sensitivity Curation Page

SERPINA1

  • Curation Status: Complete

Location Information

Select assembly: (NC_000014.8) (NC_000014.9)

Haploinsufficiency phenotype comments:

Variants in SERPINA1 are associated with alpha-1 antitrypsin deficiency. Mostly sequence/gene level variants in HGMD/OMIM ranging from minor substitutions, deletions, or insertions within the a1AT coding exons II-V have been reported. In particular, PI*Z, the most common pathogenic allele, or null alleles (e.g., PI*SZ) result in functionally deficient AAT protein (see GeneReviews). Individuals with biallelic null variants produce no measurable serum AAT. Because there is no protein to accumulate in the liver, these individuals are not at increased risk of developing liver disease; however, they are at high risk of developing lung disease; see GeneReviews for additional information.

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity