SERPINI1
Chr 3ADserpin family I member 1
Also known as: HNS-S1, HNS-S2, PI12, neuroserpin
This gene encodes neuroserpin, a serine protease inhibitor that inhibits plasminogen activators and protects neurons from plasmin-mediated damage while regulating synaptic plasticity. Mutations cause familial encephalopathy with neuroserpin inclusion bodies (FENIB), an autosomal dominant condition characterized by progressive encephalopathy and epilepsy. The gene shows tolerance to loss-of-function variants (low pLI), suggesting the pathology arises through a different mechanism than simple protein loss.
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 (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative 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
SERPINI1 · 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
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools