SERPINI1

serpin family I member 1, the group of Serpin peptidase inhibitors

Basic information

Region (hg38): 3:167735243-167825569

Previous symbols: [ "PI12" ]

Links

ENSG00000163536 ∙ NCBI:5274 ∙ OMIM:602445 ∙ HGNC:8943 ∙ Uniprot:Q99574 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• familial encephalopathy with neuroserpin inclusion bodies (Strong), mode of inheritance: AD
• familial encephalopathy with neuroserpin inclusion bodies (Supportive), mode of inheritance: AD
• progressive myoclonus epilepsy (Definitive), mode of inheritance: AD
• familial encephalopathy with neuroserpin inclusion bodies (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Encephalopathy, familial, with neuroserpin inclusion bodies	AD	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Neurologic	10517635; 12103288

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINI1 gene.

• Familial_encephalopathy_with_neuroserpin_inclusion_bodies (330 variants)
• Inborn_genetic_diseases (38 variants)
• not_provided (22 variants)
• SERPINI1-related_disorder (10 variants)
• not_specified (9 variants)
• Abnormality_of_the_nervous_system (1 variants)
• Cerebral_cavernous_malformation (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINI1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001122752.2. Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	64	1	66
missense	5	1	187	18	4	215
nonsense			3			3
start loss						0
frameshift			3			3
splice donor/acceptor (+/-2bp)			1			1
Total	5	1	195	82	5

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPINI1	protein_coding	protein_coding	ENST00000295777	8	90326

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0266	0.971	125731	0	13	125744	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.419	194	211	0.919	0.00000968	2742
Missense in Polyphen		63	81.588	0.77217		1086
Synonymous	0.702	64	71.6	0.894	0.00000330	739
Loss of Function	2.68	6	18.4	0.326	8.72e-7	232

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.000109	0.000109
Finnish	0.0000463	0.0000462
European (Non-Finnish)	0.0000264	0.0000264
Middle Eastern	0.000109	0.000109
South Asian	0.000131	0.000131
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Serine protease inhibitor that inhibits plasminogen activators and plasmin but not thrombin (PubMed:9442076, PubMed:26329378, PubMed:19265707, PubMed:19285087, PubMed:11880376). May be involved in the formation or reorganization of synaptic connections as well as for synaptic plasticity in the adult nervous system. May protect neurons from cell damage by tissue-type plasminogen activator (Probable). {ECO:0000269|PubMed:11880376, ECO:0000269|PubMed:19265707, ECO:0000269|PubMed:19285087, ECO:0000269|PubMed:26329378, ECO:0000269|PubMed:9442076, ECO:0000305}.
• Pathway: Validated targets of C-MYC transcriptional activation (Consensus)

Recessive Scores

• pRec: 0.232

Intolerance Scores

• loftool: 0.0614
• rvis_EVS: 1.15
• rvis_percentile_EVS: 92.47

Haploinsufficiency Scores

• pHI: 0.653
• hipred: Y
• hipred_score: 0.699
• ghis: 0.409

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.655

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Serpini1
• Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan)

Gene ontology

• Biological process: central nervous system development;peripheral nervous system development;negative regulation of endopeptidase activity;positive regulation of neuron projection development;regulation of cell adhesion
• Cellular component: extracellular space;secretory granule lumen;neuronal cell body;perikaryon;cytoplasmic vesicle lumen;extracellular exosome
• Molecular function: serine-type endopeptidase inhibitor activity