SERPINI1 (serpin family I member 1)

Gene

• Entrez ID: 5274
• Gene name: Serpin family I member 1
• Gene symbol: SERPINI1
• Synonyms (NCBI Gene): HNS-S1, HNS-S2, PI12, neuroserpin
• Chromosome: 3
• Chromosome location: 3q26.1
• Summary: 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 t

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs121909051	T>C	Pathogenic	Missense variant, coding sequence variant
rs121909052	A>G	Pathogenic	Missense variant, coding sequence variant
rs121909053	G>A	Pathogenic	Missense variant, coding sequence variant
rs121909054	G>A	Pathogenic	Missense variant, coding sequence variant
rs1577418477	A>C	Pathogenic	Missense variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT030837	hsa-miR-21-5p	Microarray	18591254
MIRT030837	hsa-miR-21-5p	Flow, Immunohistochemistry, Luciferase reporter assay, Microarray, qRT-PCR, Western blot	22464652

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IBA
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IDA	9442076, 19285087
GO:0004867	Function	Serine-type endopeptidase inhibitor activity	IEA
GO:0005576	Component	Extracellular region	IEA
GO:0005615	Component	Extracellular space	IBA
GO:0005615	Component	Extracellular space	IDA	17040209
GO:0005615	Component	Extracellular space	IEA
GO:0007417	Process	Central nervous system development	TAS	9070919
GO:0007422	Process	Peripheral nervous system development	TAS	9070919
GO:0010976	Process	Positive regulation of neuron projection development	ISS
GO:0030414	Function	Peptidase inhibitor activity	IEA
GO:0031410	Component	Cytoplasmic vesicle	IEA
GO:0034774	Component	Secretory granule lumen	IEA
GO:0043025	Component	Neuronal cell body	IDA	17040209
GO:0043025	Component	Neuronal cell body	IEA
GO:0043204	Component	Perikaryon	IEA
GO:0060205	Component	Cytoplasmic vesicle lumen	IDA	17040209
GO:0070062	Component	Extracellular exosome	HDA	23533145

Other IDs

• MIM: 602445
• HGNC: 8943
• e!Ensembl: ENSG00000163536

Protein

• UniProt ID: Q99574
• Protein name: Neuroserpin (Peptidase inhibitor 12) (PI-12) (Serpin I1)
• Protein function: Serine protease inhibitor that inhibits plasminogen activators and plasmin but not thrombin (PubMed:11880376, PubMed:19265707, PubMed:19285087, PubMed:26329378, PubMed:9442076). May be involved in the formation or reorganization of synaptic conn
• PDB: 3F02, 3F5N, 3FGQ
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00079	Serpin	24 → 397	Serpin (serine protease inhibitor)	Domain

• Tissue specificity: TISSUE SPECIFICITY: Detected in brain cortex and hippocampus pyramidal neurons (at protein level) (PubMed:17040209). Detected in cerebrospinal fluid (at protein level) (PubMed:25326458). Predominantly expressed in the brain (PubMed:9070919). {ECO:0000269|
• Sequence:

  MAFLGLFSLLVLQSMATGATFPEEAIADLSVNMYNRLRATGEDENILFSPLSIALAMGMM
  ELGAQGSTQKEIRHSMGYDSLKNGEEFSFLKEFSNMVTAKESQYVMKIANSLFVQNGFHV
  NEEFLQMMKKYFNAAVNHVDFSQNVAVANYINKWVENNTNNLVKDLVSPRDFDAATYLAL
  INAVYFKGNWKSQFRPENTRTFSFTKDDESEVQIPMMYQQGEFYYGEFSDGSNEAGGIYQ
  VLEIPYEGDEISMMLVLSRQEVPLATLEPLVKAQLVEEWANSVKKQKVEVYLPRFTVEQE
  IDLKDVLKALGITEIFIKDANLTGLSDNKEIFLSKAIHKSFLEVNEEGSEAAAVSGMIAI
  SRMAVLYPQVIVDHPFFFLIRNRRTGTILFMGRVMHPETMNTSGHDFEEL

• Sequence length: 410

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the nervous system	Likely pathogenic; Pathogenic	rs121909053	RCV001813962	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Pathogenic; Likely pathogenic	rs121909054, rs121909051, rs1577418477, rs121909052, rs121909053	RCV002250343 RCV000007502 RCV000007503 RCV000007504 RCV000007505 RCV000007506	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CAVERNOUS HEMANGIOMA OF BRAIN	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL NEUROLOGIC ANOMALIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
DIABETIC RETINOPATHY	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HYPERTENSION	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Ovarian serous cystadenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROGRESSIVE MYOCLONUS EPILEPSY	—	ClinGen, ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCHIZOPHRENIA	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SERPINI1-related disorder	Benign; Uncertain significance; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine carcinosarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Action Myoclonus-Renal Failure Syndrome	Action Myoclonus-Renal Failure Syndrome	CTD_human_DG	25401298		★☆☆☆☆ Found in Text Mining only
Alzheimer Disease	Alzheimer disease	Pubtator	24036060	Associate	★☆☆☆☆ Found in Text Mining only
Atkin syndrome	Atkin-Flaitz syndrome	BEFREE	30049290		★☆☆☆☆ Found in Text Mining only
Atrophy	Atrophy	Pubtator	38166833	Associate	★☆☆☆☆ Found in Text Mining only
Attention Deficit Disorder with Hyperactivity	Attention deficit hyperactivity disorder	Pubtator	38166833	Associate	★☆☆☆☆ Found in Text Mining only
Atypical Inclusion-Body Disease	Inclusion-Body Disease	CTD_human_DG	25401298		★☆☆☆☆ Found in Text Mining only
Auditory Perceptual Disorders	Auditory perceptual disorder	Pubtator	38166833	Associate	★☆☆☆☆ Found in Text Mining only
Blood Coagulation Disorders	Blood coagulation disorder	Pubtator	28747664	Associate	★☆☆☆☆ Found in Text Mining only
Body Weight	Body weight	Pubtator	10595921	Associate	★☆☆☆☆ Found in Text Mining only
Brain Diseases	Brain disease	Pubtator	10595921, 17212813, 21435071, 26732982	Associate	★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain Neoplasms	BEFREE	17212813, 19442737		★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain neoplasms	Pubtator	17212813	Inhibit	★☆☆☆☆ Found in Text Mining only
Brain Neoplasms	Brain neoplasms	Pubtator	28747664	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	24369324	Stimulate	★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebral Infarction	Ischemic stroke	Pubtator	17961231	Associate	★☆☆☆☆ Found in Text Mining only
CNS disorder	CNS Disorder	BEFREE	19442737		★☆☆☆☆ Found in Text Mining only
Colorectal Carcinoma	Colorectal Cancer	BEFREE	26892864		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	23443137	Associate	★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	LHGDN	15090543, 15664988		★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	Pubtator	15291813, 26329378, 26732982, 28230174	Associate	★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	BEFREE	27618835, 29525180		★☆☆☆☆ Found in Text Mining only
Dementia	Dementia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Dentatorubral-Pallidoluysian Atrophy	Dentatorubral Pallidoluysian Atrophy	CTD_human_DG	25401298		★☆☆☆☆ Found in Text Mining only
Dysarthria	Dysarthria	HPO_DG			★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	BEFREE	21435071, 30194596		★☆☆☆☆ Found in Text Mining only
Encephalopathies	Epileptic encephalopathy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Epilepsies Myoclonic	Myoclonic epilepsy	Pubtator	21435071, 38166833	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	Pubtator	15291813, 28230174	Associate	★☆☆☆☆ Found in Text Mining only
Familial Dementia	Dementia	BEFREE	15291813, 21115126		★☆☆☆☆ Found in Text Mining only
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	UNIPROT_DG	10517635, 11880376		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	BEFREE	11914409, 12112652, 15291813, 21115126, 30049290		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	GENOMICS_ENGLAND_DG	12103288		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	ORPHANET_DG	12103288		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	Orphanet			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	CLINVAR_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial encephalopathy with neuroserpin inclusion bodies	Encephalopathy With Neuroserpin Inclusion Bodies	CTD_human_DG			★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Familial Progressive Myoclonic Epilepsy	Myoclonic Epilepsy	CTD_human_DG	25401298		★☆☆☆☆ Found in Text Mining only
Frontotemporal dementia	Frontotemporal dementia	BEFREE	11914409		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	19423540		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	Pubtator	19423540	Associate	★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	19423540		★☆☆☆☆ Found in Text Mining only
Glioma	Glioma	Pubtator	36295489	Associate	★☆☆☆☆ Found in Text Mining only
Hepatitis C Chronic	Hepatitis c	Pubtator	24369324	Associate	★☆☆☆☆ Found in Text Mining only
Hypocholesterolemia	Hypocholesterolemia	BEFREE	28255164		★☆☆☆☆ Found in Text Mining only
Ischemic stroke	Ischemic Stroke	BEFREE	14983220		★☆☆☆☆ Found in Text Mining only
Lafora Disease	Lafora Disease	BEFREE	30049290		★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	24369324		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of brain	Brain Neoplasms	BEFREE	19442737		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of prostate	Prostate cancer	BEFREE	15723353		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of stomach	Stomach Neoplasms	BEFREE	22464652		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	23443137		★☆☆☆☆ Found in Text Mining only
May-White Syndrome	May-White Syndrome	CTD_human_DG	25401298		★☆☆☆☆ Found in Text Mining only
Multiple Sclerosis	Multiple sclerosis	Pubtator	21435071	Associate	★☆☆☆☆ Found in Text Mining only
Myoclonic Epilepsies, Progressive	Myoclonic epilepsy	LHGDN	17606885		★☆☆☆☆ Found in Text Mining only
Myoclonic Epilepsies, Progressive	Myoclonic epilepsy	CTD_human_DG	25401298		★☆☆☆☆ Found in Text Mining only
Myoclonic Epilepsies, Progressive	Myoclonic epilepsy	BEFREE	28631894		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	22464652		★☆☆☆☆ Found in Text Mining only
Neurodegenerative Diseases	Neurodegenerative disorder	Pubtator	11141496, 26329378	Associate	★☆☆☆☆ Found in Text Mining only
Neurodegenerative Disorders	Neurodegenerative Disorders	BEFREE	30049290		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Ovarian Neoplasms	Ovarian neoplasm	Pubtator	32441301	Associate	★☆☆☆☆ Found in Text Mining only
Pick Disease of the Brain	Pica	BEFREE	11914409		★☆☆☆☆ Found in Text Mining only
Presenile dementia	Senile Dementia	BEFREE	27618835, 29525180		★☆☆☆☆ Found in Text Mining only
Prostate carcinoma	Prostate cancer	BEFREE	15723353		★☆☆☆☆ Found in Text Mining only
Pulmonary Emphysema	Pulmonary Emphysema	BEFREE	30194596		★☆☆☆☆ Found in Text Mining only
Schizophrenia	Schizophrenia	BEFREE	15176481		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Schizophrenia	Schizophrenia	PSYGENET_DG	15176481		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Status Epilepticus	Status Epilepticus	LHGDN	18591508		★☆☆☆☆ Found in Text Mining only
Stomach Neoplasms	Stomach neoplasms	Pubtator	22464652	Associate	★☆☆☆☆ Found in Text Mining only
Stroke	Stroke	Pubtator	17961231	Associate	★☆☆☆☆ Found in Text Mining only
Unverricht-Lundborg Syndrome	Myoclonic Epilepsy	BEFREE	28631894		★☆☆☆☆ Found in Text Mining only