SAA1
protein-codingserum amyloid A1, the group of Receptor ligands
Gene summary
This gene encodes a member of the serum amyloid A family of apolipoproteins. The encoded preproprotein is proteolytically processed to generate the mature protein. This protein is a major acute phase protein that is highly expressed in response to inflammation and tissue injury. This protein also plays an important role in HDL metabolism and cholesterol homeostasis. High levels of this protein are associated with chronic inflammatory diseases including atherosclerosis, rheumatoid arthritis, Alzheimer's disease and Crohn's disease. This protein may also be a potential biomarker for certain tumors. Finally, antimicrobial activity against S. aureus and E. coli resides in the N-terminal portion of the mature protein. Alternate splicing results in multiple transcript variants that encode the same protein. A pseudogene of this gene is found on chromosome 11. [provided by RefSeq, Jul 2020]
- SAA
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~3.7 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 SAA1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199161.5. 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 | 1 | 1 | ||||
| missense | 18 | 4 | 2 | 24 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 18 | 5 | 3 | 26 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_954630.2 | 3 | MANE Select | |
| Ensembl | ENSP00000348918.4 | 3 | MANE Select | |
| RefSeq | NP_000322.3 | 3 | Standard | |
| RefSeq | NP_001171477.2 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Selenium Micronutrient Network
- Vitamin B12 Metabolism
- Folate Metabolism
- Interleukin-4 and 13 signaling
- Signaling by GPCR
Biological Process
- activation of MAPK activity
- receptor-mediated endocytosis
- acute-phase response
- G protein-coupled receptor signaling pathway
- positive regulation of cytosolic calcium ion concentration
Molecular Function
- G protein-coupled receptor binding
- heparin binding
- chemoattractant activity
Cellular Component
- extracellular region
- extracellular space
- cytoplasmic microtubule
- high-density lipoprotein particle
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000405158
- Coding exons
- 3
- Length
- 3804
- Individuals with no LoFs
- 125690
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 57
- Defined
- 125747
- p
- 0.000227
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0155 | 68 | 68.4 | 0.995 | 0.00000389 | 783 |
| Missense (PolyPhen) | 23 | 23.191 | 0.99178 | 315 | ||
| Synonymous | -0.256 | 29 | 27.3 | 1.06 | 0.00000168 | 232 |
| Loss of Function | 0.647 | 3 | 4.48 | 0.670 | 3.41e-7 | 42 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00013 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.0029 | 0.0024 | notable |
| East Asian | 0.00012 | 0.00011 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00012 | rare |
| South Asian | 0.00044 | 0.00042 | rare |
| Other | 0.00039 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Major acute phase protein.;
- Disease
- DISEASE: Note=Reactive, secondary amyloidosis is characterized by the extracellular accumulation in various tissues of the SAA1 protein. These deposits are highly insoluble and resistant to proteolysis; they disrupt tissue structure and compromise function. {ECO:0000269|PubMed:1463770}.; DISEASE: Note=Elevated serum SAA1 protein levels may be associated with lung cancer. {ECO:0000269|PubMed:1463770}.;
Recessive Scores
- pRec
- 0.518
Intolerance Scores
- LoFtool
- 0.985
- RVIS EVS
- 0.1
- RVIS percentile EVS
- 61.28
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.670
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |