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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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SERPINI1
serpin family I member 1
Chromosome 3 Β· 3q26.1
NCBI Gene: 5274Ensembl: ENSG00000163536.14HGNC: HGNC:8943UniProt: A0A0S2Z455
66PubMed Papers
21Diseases
0Drugs
6Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
neuronal cell bodyextracellular exosomeGO:0005615serine-type endopeptidase inhibitor activityfamilial encephalopathy with neuroserpin inclusion bodieshypertensionprogressive myoclonus epilepsycardiovascular disease
✦AI Summary

SERPINI1 encodes neuroserpin, a serine protease inhibitor that inhibits plasminogen activators and plasmin 1. The protein functions in nervous system development and synaptic plasticity, with potential neuroprotective roles against tissue-type plasminogen activator damage [UniProt annotation]. SERPINI1 plays critical roles in neuronal axon extension and motoneuron development, as demonstrated by studies showing that loss of serpini1 function results in axon defects and anxiety-like behavior in zebrafish 2. Pathogenic SERPINI1 variants cause familial encephalopathy with neuroserpin inclusion bodies (FENIB), a rare neurodegenerative disorder characterized by progressive cognitive decline, myoclonus, and seizures 3. FENIB results from neuroserpin polymerization and intracellular aggregation 4. The disease typically presents in late childhood or early adulthood with median onset at 21 years and median death at 33 years, with 69% of patients showing poor response to antiseizure medications 3. Cerebral and cerebellar atrophy occur in approximately 69% of cases 3. Beyond neurological disease, SERPINI1 exhibits tumor-suppressive function in gastric cancer, where miR-21-mediated downregulation of SERPINI1 promotes cell cycle progression and tumor growth 5. Additionally, SERPINI1 levels are significantly reduced in aqueous humor of patients with primary open-angle glaucoma, suggesting potential involvement in ocular pathology 6.

Sources cited
1
SERPINI1 pathogenic variants cause FENIB with progressive cognitive decline, myoclonus, seizures; median disease onset 21 years, median death 33 years; 69% ASM-resistant; 69% show cerebral/cerebellar atrophy
PMID: 36417830
2
Loss of serpini1 function causes anxiety-like behavior and motoneuron axon extension defects in zebrafish
PMID: 33168193
3
SERPINI1 has tumor-suppressive function in gastric cancer; miR-21 downregulates SERPINI1 to promote G1/S progression
PMID: 22464652
4
FENIB is caused by neuroserpin polymerization and intracellular aggregation
PMID: 30194596
5
SERPINI1 levels are significantly reduced in aqueous humor of POAG patients (FC=0.26)
PMID: 40389884
6
SERPINI1 inhibits plasminogen activators and plasmin
PMID: 11880376
Disease Associationsβ“˜21
familial encephalopathy with neuroserpin inclusion bodiesOpen Targets
0.72Strong
hypertensionOpen Targets
0.52Moderate
progressive myoclonus epilepsyOpen Targets
0.37Weak
cardiovascular diseaseOpen Targets
0.35Weak
Abnormality of the nervous systemOpen Targets
0.27Weak
bone neoplasmOpen Targets
0.26Weak
connective tissue neoplasmOpen Targets
0.26Weak
genetic disorderOpen Targets
0.19Weak
Transient global amnesiaOpen Targets
0.18Weak
nephrotic syndromeOpen Targets
0.13Weak
hepatocellular carcinomaOpen Targets
0.08Suggestive
drug allergyOpen Targets
0.07Suggestive
scleritisOpen Targets
0.06Suggestive
major depressive disorderOpen Targets
0.06Suggestive
keratoconjunctivitisOpen Targets
0.06Suggestive
obsessive-compulsive disorderOpen Targets
0.05Suggestive
attention deficit hyperactivity disorderOpen Targets
0.05Suggestive
glioblastoma multiformeOpen Targets
0.05Suggestive
retinal degenerationOpen Targets
0.05Suggestive
musculoskeletal system diseaseOpen Targets
0.04Suggestive
Encephalopathy, familial, with neuroserpin inclusion bodiesUniProt
Pathogenic Variants6
NM_001122752.2(SERPINI1):c.1175G>A (p.Gly392Glu)Pathogenic
Familial encephalopathy with neuroserpin inclusion bodies|Abnormality of the nervous system
β˜…β˜…β˜†β˜†2022β†’ Residue 392
NM_001122752.2(SERPINI1):c.145T>C (p.Ser49Pro)Pathogenic
Familial encephalopathy with neuroserpin inclusion bodies
β˜…β˜†β˜†β˜†2024β†’ Residue 49
NM_001122752.2(SERPINI1):c.1174G>C (p.Gly392Arg)Pathogenic
Familial encephalopathy with neuroserpin inclusion bodies
β˜…β˜†β˜†β˜†2022β†’ Residue 392
NM_001122752.2(SERPINI1):c.1174G>A (p.Gly392Arg)Pathogenic
Familial encephalopathy with neuroserpin inclusion bodies
β˜…β˜†β˜†β˜†2016β†’ Residue 392
NM_001122752.2(SERPINI1):c.154A>C (p.Ser52Arg)Pathogenic
Familial encephalopathy with neuroserpin inclusion bodies
β˜†β˜†β˜†β˜†2004β†’ Residue 52
NM_001122752.2(SERPINI1):c.1013A>G (p.His338Arg)Pathogenic
Familial encephalopathy with neuroserpin inclusion bodies
β˜†β˜†β˜†β˜†2002β†’ Residue 338
View on ClinVar β†—
Related Genes
PLATProtein interaction87%ALDH3A2Shared pathway40%ZIC5Shared pathway33%ZIC4Shared pathway33%SNTG2Shared pathway33%JRKLShared pathway33%
Tissue Expression6 tissues
Brain
100%
Heart
16%
Bone Marrow
9%
Ovary
3%
Lung
2%
Liver
1%
Gene Interaction Network
Click a node to explore
SERPINI1PLATALDH3A2ZIC5ZIC4SNTG2JRKL
PROTEIN STRUCTURE
Preparing viewer…
PDB3F02 Β· 1.80 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.46Moderately Constrained
pLIβ“˜
0.99Intolerant
Observed/Expected LoF0.23 [0.13–0.46]
RankingsWhere SERPINI1 stands among ~20K protein-coding genes
  • #7,120of 20,598
    Most Researched66
  • #3,371of 5,498
    Most Pathogenic Variants6
  • #2,588of 17,882
    Most Constrained (LOEUF)0.46 Β· top quartile
Genes detectedSERPINI1
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Role of SERPINI1 pathogenic variants in familial encephalopathy with neuroserpin inclusion bodies: A case report and literature review.
PMID: 36417830
Seizure Β· 2022
1.00
2
Increased anxiety was found in serpini1 knockout zebrafish larval.
PMID: 33168193
Biochem Biophys Res Commun Β· 2021
0.90
3
MicroRNA-21 inhibits Serpini1, a gene with novel tumour suppressive effects in gastric cancer.
PMID: 22464652
Dig Liver Dis Β· 2012
0.80
4
Familial conformational diseases and dementias.
PMID: 12112652
Hum Mutat Β· 2002
0.70
5
Cellular Models for the Serpinopathies.
PMID: 30194596
Methods Mol Biol Β· 2018
0.60