SERPINF2
Chr 17ARserpin family F member 2
Also known as: A2AP, AAP, ALPHA-2-PI, API, PLI, alpha2AP
This protein is a serine protease inhibitor that serves as the major inhibitor of plasmin, thereby regulating fibrin degradation and blood clotting. Mutations cause alpha-2-plasmin inhibitor deficiency, an autosomal recessive bleeding disorder characterized by severe hemorrhagic diathesis due to impaired regulation of the coagulation pathway. The gene shows tolerance to loss-of-function variants (low pLI), consistent with the recessive inheritance pattern where heterozygous carriers are typically unaffected.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
SERPINF2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
External Resources
Links to major genomics databases and tools