SERPING1

serpin family G member 1, the group of Serpin peptidase inhibitors|Complement system regulators and receptors

Basic information

Region (hg38): 11:57597387-57619171

Previous symbols: [ "C1NH" ]

Links

ENSG00000149131

∙ NCBI:710 ∙ OMIM:606860 ∙ HGNC:1228 ∙ Uniprot:P05155 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

hereditary angioedema type 1 (Supportive), mode of inheritance: AD
hereditary angioedema type 2 (Supportive), mode of inheritance: AD
C1 inhibitor deficiency (Supportive), mode of inheritance: AD
hereditary angioedema with C1Inh deficiency (Strong), mode of inheritance: AD
hereditary angioedema with C1Inh deficiency (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Angioedema, hereditary, 1	AD/AR	Allergy/Immunology/Infectious	Medical treatment (eg, with C1 inhibitor concentrate, ecallantide, icatabant) may be beneficial to prevent and/or treat acute attacks	Allergy/Immunology/Infectious; Gastrointestinal	4393526; 4551861; 792688; 7091182; 3587308; 3653633; 3056508; 3693762; 2723063; 2365061; 2296585; 1885769; 1684567; 1339401; 1459574; 8396558; 8330878; 7618673; 7883978; 8755917; 8628358; 11700154; 11743247; 15971231; 16470590; 16813612 ; 17137866; 17502473; 19752569; 20695852; 20818887; 20818888; 20818886; 21208117; 21864911; 22748405; 22800873; 22831796; 22882460; 23123409; 23437219; 23583915; 23607500; 23678554; 23689237

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPING1 gene.

not_provided (448 variants)
Hereditary_angioedema_type_1 (283 variants)
Inborn_genetic_diseases (61 variants)
Hereditary_angioedema_with_C1Inh_deficiency (35 variants)
SERPING1-related_disorder (20 variants)
Angioedema (14 variants)
C1_inhibitor_deficiency (9 variants)
not_specified (7 variants)
Hereditary_C1_esterase_inhibitor_deficiency_-_dysfunctional_factor (6 variants)
Complement_component_4,_partial_deficiency_of,_due_to_dysfunctional_c1_inhibitor (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPING1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000062.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous	1 clinvar		3 clinvar	95 clinvar	1 clinvar	100
missense	57 clinvar	67 clinvar	174 clinvar	30 clinvar	4 clinvar	332
nonsense	50 clinvar	1 clinvar				51
start loss	3					3
frameshift	123 clinvar	16 clinvar		1 clinvar		140
splice donor/acceptor (+/-2bp)	34 clinvar	6 clinvar	1 clinvar			41
Total	268	90	178	126	5

Highest pathogenic variant AF is 0.0000065719432

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
SERPING1	protein_coding	protein_coding	ENST00000278407	7	17467

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.964	0.0365	125733	0	1	125734	0.00000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.06	213	261	0.815	0.0000143	3275
Missense in Polyphen		31	75.798	0.40898		1010
Synonymous	-0.190	111	108	1.02	0.00000608	1040
Loss of Function	3.31	1	14.7	0.0680	6.54e-7	195

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Activation of the C1 complex is under control of the C1- inhibitor. It forms a proteolytically inactive stoichiometric complex with the C1r or C1s proteases. May play a potentially crucial role in regulating important physiological pathways including complement activation, blood coagulation, fibrinolysis and the generation of kinins. Very efficient inhibitor of FXIIa. Inhibits chymotrypsin and kallikrein. {ECO:0000269|PubMed:8495195}.;
Disease: DISEASE: Hereditary angioedema (HAE) [MIM:106100]: An autosomal dominant disorder characterized by episodic local swelling involving subcutaneous or submucous tissue of the upper respiratory and gastrointestinal tracts, face, extremities, and genitalia. Hereditary angioedema due to C1 esterase inhibitor deficiency is comprised of two clinically indistinguishable forms. In hereditary angioedema type 1, serum levels of C1 esterase inhibitor are decreased, while in type 2, the levels are normal or elevated, but the protein is non-functional. {ECO:0000269|PubMed:12773530, ECO:0000269|PubMed:1363816, ECO:0000269|PubMed:1451784, ECO:0000269|PubMed:14635117, ECO:0000269|PubMed:16409206, ECO:0000269|PubMed:2118657, ECO:0000269|PubMed:2296585, ECO:0000269|PubMed:22994404, ECO:0000269|PubMed:2365061, ECO:0000269|PubMed:24456027, ECO:0000269|PubMed:3178731, ECO:0000269|PubMed:7814636, ECO:0000269|PubMed:7883978, ECO:0000269|PubMed:8172583, ECO:0000269|PubMed:8529136, ECO:0000269|PubMed:8755917, ECO:0000269|Ref.41}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Complement and coagulation cascades - Homo sapiens (human);Pertussis - Homo sapiens (human);Human Complement System;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;intrinsic prothrombin activation pathway;Innate Immune System;Immune System;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Intrinsic Pathway of Fibrin Clot Formation;Hemostasis;Formation of Fibrin Clot (Clotting Cascade);Regulation of Complement cascade;Complement cascade (Consensus)

Recessive Scores

pRec: 0.215

Intolerance Scores

loftool: 0.00565
rvis_EVS: -0.65
rvis_percentile_EVS: 16.44

Haploinsufficiency Scores

pHI: 0.105
hipred: Y
hipred_score: 0.594
ghis: 0.599

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: N
gene_indispensability_score: 0.458

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Serping1
Phenotype: cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype;

Gene ontology

Biological process: negative regulation of complement activation, lectin pathway;platelet degranulation;complement activation, classical pathway;aging;blood coagulation, intrinsic pathway;blood circulation;negative regulation of endopeptidase activity;regulation of complement activation;fibrinolysis;innate immune response
Cellular component: extracellular region;extracellular space;platelet alpha granule lumen;collagen-containing extracellular matrix;extracellular exosome;blood microparticle
Molecular function: serine-type endopeptidase inhibitor activity;protein binding