SERPINI1

Chr 3

serpin family I member 1

Also known as: HNS-S1, HNS-S2, PI12, neuroserpin

NCBI Gene: 5274 ENSG00000163536 UniProt: Q99574

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.

ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the serpin superfamily of serine proteinase inhibitors. The protein is primarily secreted by axons in the brain, and preferentially reacts with and inhibits tissue-type plasminogen activator. It is thought to play a role in the regulation of axonal growth and the development of synaptic plasticity. Mutations in this gene result in familial encephalopathy with neuroserpin inclusion bodies (FENIB), which is a dominantly inherited form of familial encephalopathy and epilepsy characterized by the accumulation of mutant neuroserpin polymers. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtEncephalopathy, familial, with neuroserpin inclusion bodies

Clinical highlights

Gene-disease validity (ClinGen)

progressive myoclonus epilepsy · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.64

LOEUF

Multiple*

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429