SERPINA3
protein-codingserpin family A member 3, the group of Serpin peptidase inhibitors
Gene summary
The protein encoded by this gene is a member of the serpin family of proteins, a group of proteins that inhibit serine proteases. This gene is one in a cluster of serpin genes located on the q arm of chromosome 14. Polymorphisms in this protein appear to be tissue specific and influence protease targeting. Variations in this protein's sequence have been implicated in Alzheimer's disease, and deficiency of this protein has been associated with liver disease. Mutations have been identified in patients with Parkinson disease and chronic obstructive pulmonary disease. [provided by RefSeq, Jun 2020]
- AACT
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~11.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to SERPINA3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001085.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 9 | 6 | 17 | ||
| missense | 1 | 70 | 16 | 87 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 2 | 1 | 3 | |||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 1 | 0 | 75 | 26 | 6 | 108 |
Highest pathogenic variant AF is 0.0000020521325
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001076.2 | 4 | MANE Select | |
| Ensembl | ENSP00000376793.3 | 4 | MANE Select | |
| RefSeq | NP_001371601.1 | 4 | Standard | |
| RefSeq | NP_001371602.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenium Micronutrient Network
- Vitamin B12 Metabolism
- Folate Metabolism
- Neutrophil degranulation
- Innate Immune System
Biological Process
- platelet degranulation
- acute-phase response
- inflammatory response
- negative regulation of endopeptidase activity
- regulation of lipid metabolic process
Molecular Function
- DNA binding
- serine-type endopeptidase inhibitor activity
- protein binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- platelet alpha granule lumen
- secretory granule lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000467132
- Coding exons
- 4
- Length
- 11679
- Individuals with no LoFs
- 125456
- Homozygous LoFs
- 1
- Heterozygous LoFs
- 291
- Defined
- 125748
- p
- 0.00116
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -1.37 | 281 | 223 | 1.26 | 0.0000125 | 2795 |
| Missense (PolyPhen) | 78 | 60.747 | 1.284 | 836 | ||
| Synonymous | -2.06 | 120 | 94.5 | 1.27 | 0.00000593 | 836 |
| Loss of Function | -1.38 | 17 | 11.9 | 1.43 | 6.02e-7 | 145 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0017 | 0.0016 | notable |
| Latino/Admixed American | 0.00067 | 0.00061 | rare |
| Ashkenazi Jewish | 0.0032 | 0.0032 | notable |
| East Asian | 0.00065 | 0.00065 | rare |
| Finnish | 0.0040 | 0.0040 | notable |
| European (Non-Finnish) | 0.0013 | 0.00070 | notable |
| South Asian | 0.00098 | 0.00095 | rare |
| Other | 0.00082 | 0.00081 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Although its physiological function is unclear, it can inhibit neutrophil cathepsin G and mast cell chymase, both of which can convert angiotensin-1 to the active angiotensin-2. {ECO:0000269|PubMed:2404007}.;
Recessive Scores
- pRec
- 0.384
Intolerance Scores
- LoFtool
- 0.227
- RVIS EVS
- -0.42
- RVIS percentile EVS
- 25.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.917
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |