GeneBe

SERPINA1

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

Basic information

Region (hg38): 14:94376747-94390693

Previous symbols: [ "PI" ]

Links

ENSG00000197249 ∙ NCBI:5265 ∙ OMIM:107400 ∙ HGNC:8941 ∙ Uniprot:P01009 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • alpha 1-antitrypsin deficiency (Limited), mode of inheritance: AR
  • alpha 1-antitrypsin deficiency (Strong), mode of inheritance: AR
  • alpha 1-antitrypsin deficiency (Supportive), mode of inheritance: AR
  • hemorrhagic disease due to alpha-1-antitrypsin Pittsburgh mutation (Supportive), mode of inheritance: AD
  • alpha 1-antitrypsin deficiency (Strong), mode of inheritance: AR
  • cystic fibrosis (Supportive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Alpha-1-Antitrypsin deficiencyARGastrointestinal; PulmonaryMedical treatment (augmentation therapy with purified alpha-1-antitrypsin, Vitamin E supplementation) can be helpful for pulmonary and hepatic manifestations; Exacerbating factors (eg, smoking) should be avoided; Liver transplantation may be necessary in individuals with severe liver manifestationsGastrointestinal; Pulmonary4240153; 4117022; 3494198; 2185272; 2035327; 7875269; 8066566; 10898319; 12740257; 11320399; 12452881; 12574076; 14522813; 15282394; 15214923; 20301692; 21457231; 21752289; 22016686; 22215832; 22330941; 22500781; 22536580; 22933512; 23055718; 23251618; 23766346

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the SERPINA1 gene.

  • Alpha-1-antitrypsin_deficiency (329 variants)
  • not_provided (94 variants)
  • SERPINA1-related_disorder (68 variants)
  • Inborn_genetic_diseases (46 variants)
  • not_specified (18 variants)
  • See_cases (2 variants)
  • Hereditary_angioedema_with_normal_C1Inh (2 variants)
  • PI_P(DUARTE) (1 variants)
  • PI_P(ST._ALBANS) (1 variants)
  • PI_Z(TUN) (1 variants)
  • PI_NULL(MATTAWA) (1 variants)
  • PI_W(BETHESDA) (1 variants)
  • PI_NULL(WEST) (1 variants)
  • PI_Q0(LUDWIGSHAFEN) (1 variants)
  • PI_Q0(GRANITE_FALLS) (1 variants)
  • PI_NULL(BOLTON) (1 variants)
  • Mitochondrial_complex_I_deficiency,_nuclear_type_21 (1 variants)
  • Hemorrhagic_disease_due_to_alpha-1-antitrypsin_Pittsburgh_mutation (1 variants)
  • PI_NULL(BELLINGHAM) (1 variants)
  • PI_Q0(NEWPORT) (1 variants)
  • Neurodevelopmental_disorder (1 variants)
  • PI_Q0(BELLINGHAM) (1 variants)
  • FRAXE (1 variants)
  • PI_F (1 variants)
  • Chronic_obstructive_pulmonary_disease (1 variants)
  • PI_I (1 variants)
  • PI_M(MALTON) (1 variants)
  • PI_Z (1 variants)
  • PI_Z(BRISTOL) (1 variants)
  • PI_M(HEERLEN) (1 variants)
  • PI_X (1 variants)
  • PI_NULL(CARDIFF) (1 variants)
  • PI_Q0(HONG_KONG_1) (1 variants)
  • Susceptibility_to_severe_coronavirus_disease_(COVID-19) (1 variants)
  • PI_M(PROCIDA) (1 variants)
  • PI_S(IIYAMA) (1 variants)
  • PI_Q0(DEVON) (1 variants)
  • PI_Z(AUGSBURG) (1 variants)
  • PI_Q0(CARDIFF) (1 variants)
  • Squamous_cell_carcinoma (1 variants)
  • PI_NULL(DEVON) (1 variants)
  • PI_NULL(HONG_KONG_1) (1 variants)
  • PI_CHRISTCHURCH (1 variants)
  • PI_V(MUNICH) (1 variants)
  • PI_Q0(BOLTON) (1 variants)
  • PI_Z(WREXHAM) (1 variants)
  • PI_NULL(NEWPORT) (1 variants)
  • PI_NULL(LUDWIGSHAFEN) (1 variants)
  • PI_P(LOWELL) (1 variants)
  • PI_M(MINERAL_SPRINGS) (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the SERPINA1 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000295.5. 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.

EffectPLPVUSLBBSum
synonymous
3
clinvar
155
clinvar
3
clinvar
 161
missense
11
clinvar
20
clinvar
79
clinvar
52
clinvar
7
clinvar
 169
nonsense
8
clinvar
6
clinvar
 14
start loss
1
1
 2
frameshift
15
clinvar
17
clinvar
2
clinvar
 34
splice donor/acceptor (+/-2bp)
3
clinvar
5
clinvar
 8
Total 38 49 82 207 12

Highest pathogenic variant AF is 0.015862918

Loading clinvar variants...

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
SERPINA1protein_codingprotein_codingENST00000448921 413947
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
6.85e-80.1501257250231257480.0000915
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-0.3732422261.070.00001212771
Missense in Polyphen5458.8820.91708778
Synonymous-0.06921031021.010.00000647825
Loss of Function0.003741111.00.9994.78e-7140

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.0003000.000300
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00009680.0000967
Middle Eastern0.00005440.0000544
South Asian0.0001310.000131
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Inhibitor of serine proteases. Its primary target is elastase, but it also has a moderate affinity for plasmin and thrombin. Irreversibly inhibits trypsin, chymotrypsin and plasminogen activator. The aberrant form inhibits insulin-induced NO synthesis in platelets, decreases coagulation time and has proteolytic activity against insulin and plasmin.;
Disease
DISEASE: Alpha-1-antitrypsin deficiency (A1ATD) [MIM:613490]: A disorder whose most common manifestation is emphysema, which becomes evident by the third to fourth decade. A less common manifestation of the deficiency is liver disease, which occurs in children and adults, and may result in cirrhosis and liver failure. Environmental factors, particularly cigarette smoking, greatly increase the risk of emphysema at an earlier age. {ECO:0000269|PubMed:1905728, ECO:0000269|PubMed:2227940, ECO:0000269|PubMed:2390072}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway
Complement and coagulation cascades - Homo sapiens (human);Nuclear Receptors Meta-Pathway;NRF2 pathway;Lung fibrosis;Dengue-2 Interactions with Complement and Coagulation Cascades;Complement and Coagulation Cascades;Neutrophil degranulation;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein phosphorylation;Post-translational protein modification;Metabolism of proteins;Innate Immune System;Immune System;p73 transcription factor network;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;Hemostasis;FOXA1 transcription factor network;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

pRec
0.798

Intolerance Scores

loftool
0.00462
rvis_EVS
0.53
rvis_percentile_EVS
81.01

Haploinsufficiency Scores

pHI
0.195
hipred
N
hipred_score
0.428
ghis
0.850

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.975

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Serpina1e
Phenotype

Gene ontology

Biological process
platelet degranulation;endoplasmic reticulum to Golgi vesicle-mediated transport;acute-phase response;blood coagulation;negative regulation of endopeptidase activity;neutrophil degranulation;post-translational protein modification;cellular protein metabolic process;COPII vesicle coating
Cellular component
Golgi membrane;extracellular region;extracellular space;endoplasmic reticulum;endoplasmic reticulum lumen;Golgi apparatus;COPII-coated ER to Golgi transport vesicle;platelet alpha granule lumen;endoplasmic reticulum-Golgi intermediate compartment membrane;intracellular membrane-bounded organelle;collagen-containing extracellular matrix;extracellular exosome;ficolin-1-rich granule lumen
Molecular function
protease binding;serine-type endopeptidase inhibitor activity;protein binding;identical protein binding