SERPINI1
Serpin Family I Member 1 (Neuroserpin)
Gene Information Card
| Symbol | SERPINI1 |
|---|---|
| Full Name | Serpin Family I Member 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 3q26.1 |
| NCBI Gene ID | 5274 ncbi.nlm.nih.gov/gene/5274 |
| Ensembl ID | ENSG00000163536 |
| UniProt ID | Q99574 |
| OMIM ID | 602445 |
| HGNC ID | 10785 |
| Aliases | neuroserpin, PI12, MGC22286 |
Description
SERPINI1 encodes neuroserpin, a member of the serine protease inhibitor (serpin) superfamily. Neuroserpin is predominantly expressed in the nervous system, where it inhibits tissue-type plasminogen activator (tPA) and regulates neuronal plasticity, synaptic function, and cell survival. Mutations in SERPINI1 cause familial encephalopathy with neuroserpin inclusion bodies (FENIB), a rare autosomal dominant neurodegenerative disorder characterized by progressive dementia, epilepsy, and intraneuronal accumulation of polymerized neuroserpin.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Familial encephalopathy with neuroserpin inclusion bodies (FENIB) | Missense mutations (e.g., Ser49Pro, Ser52Arg) cause conformational instability and polymerization of neuroserpin, leading to intraneuronal inclusion bodies and neurodegeneration. | OMIM #604218; ClinVar; multiple case reports |
| Epilepsy (partial, with cognitive decline) | Neuroserpin dysfunction disrupts tPA/plasminogen system in the CNS, impairing synaptic remodeling and neuronal excitability. | ClinVar; literature review |
| Dementia (progressive, early-onset) | Accumulation of neuroserpin polymers in neurons of the cerebral cortex and basal ganglia leads to cognitive decline. | OMIM; neuropathological studies |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (cerebral cortex) | 32.5 | High |
| Brain (hippocampus) | 28.1 | High |
| Brain (cerebellum) | 15.3 | Medium |
| Spinal cord | 12.0 | Medium |
| Testis | 4.2 | Low |
| Heart | 1.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 45.0 | High expression; used in neuroserpin studies |
| U-87 MG (glioblastoma) | 22.3 | Moderate expression |
| HEK293 (embryonic kidney) | 3.5 | Low endogenous expression; common for recombinant studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.145T>C (p.Ser49Pro) | Missense | Rare (founder mutation in UK families) | Causes FENIB; promotes polymerization and inclusion body formation |
| c.156C>A (p.Ser52Arg) | Missense | Rare (reported in European families) | Causes FENIB; severe phenotype with early-onset dementia |
| c.227G>A (p.Gly76Glu) | Missense | Rare | Associated with FENIB; reduced inhibitory activity |
| c.2T>C (p.Met1Thr) | Start loss | Very rare | Likely loss of function; incomplete penetrance |
Mutation functional classification
Loss of Function (LOF)
Start loss mutations (e.g., p.Met1Thr) reduce neuroserpin production, impairing tPA inhibition and synaptic regulation.
Gain of Function (GOF)
Not clearly established; most pathogenic mutations cause toxic gain-of-function via polymerization.
Dominant Negative (DN)
Polymerogenic mutations (e.g., Ser49Pro, Ser52Arg) act as dominant negatives by forming intracellular aggregates that sequester wild-type neuroserpin and disrupt cellular proteostasis.
View complete mutation data：
Gene Ontology (GO)
Pathways
• REACT:147422 – Peptide ligand-binding receptors
• REACT:111102 – Signal transduction by p53 class mediator
• WP:WP4223 – Serpinopathies
• WP:WP3932 – Alzheimer's disease and miRNA effects
Protein Summary
Neuroserpin is a 410-amino-acid glycoprotein (45 kDa) belonging to the serpin family. It is secreted by neurons and inhibits tissue-type plasminogen activator (tPA) in the extracellular matrix of the CNS. The protein adopts a metastable native conformation; pathogenic mutations destabilize the structure, leading to polymerization and accumulation as inclusion bodies (Collins bodies) in the endoplasmic reticulum of neurons. This results in progressive neurodegeneration, particularly in the cerebral cortex, hippocampus, and substantia nigra. Neuroserpin also plays roles in synaptic plasticity, learning, and memory.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| SERPINI1 Knockout HEK293 Cell Line | EDJ-KQ5456 | Human | 5274 | Details Get a Quote |
| SERPINI1 Knockout A-549 Cell Line | EDJ-KQ28650 | Human | 5274 | Details Get a Quote |
| SERPINI1 Knockout HCT 116 Cell Line | EDJ-KQ28651 | Human | 5274 | Details Get a Quote |
| SERPINI1 Knockout HeLa Cell Line | EDJ-KQ28652 | Human | 5274 | Details Get a Quote |
