OAS3
protein-coding2'-5'-oligoadenylate synthetase 3, the group of 2'-5'-oligoadenylate synthetase family
Gene summary
This gene encodes an enzyme included in the 2', 5' oligoadenylate synthase family. This enzyme is induced by interferons and catalyzes the 2', 5' oligomers of adenosine in order to bind and activate RNase L. This enzyme family plays a significant role in the inhibition of cellular protein synthesis and viral infection resistance. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~38.4 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 OAS3 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_006187.4. 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 | 1 | 3 | |||
| missense | 172 | 8 | 3 | 183 | ||
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 180 | 8 | 5 | 193 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_006178.2 | 16 | MANE Select | |
| Ensembl | ENSP00000228928.7 | 16 | MANE Select | |
| RefSeq | NP_001397913.1 | 16 | Standard | |
| Ensembl | ENSP00000448388.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Influenza A - Homo sapiens (human)
- NOD-like receptor signaling pathway - Homo sapiens (human)
- Hepatitis C - Homo sapiens (human)
- Measles - Homo sapiens (human)
- Herpes simplex infection - Homo sapiens (human)
Biological Process
- nucleobase-containing compound metabolic process
- response to virus
- negative regulation of viral genome replication
- defense response to virus
- interferon-gamma-mediated signaling pathway
Molecular Function
- 2'-5'-oligoadenylate synthetase activity
- double-stranded RNA binding
- protein binding
- ATP binding
- metal ion binding
Cellular Component
- extracellular space
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000228928
- Coding exons
- 16
- Length
- 34898
- Individuals with no LoFs
- 121765
- Homozygous LoFs
- 21
- Heterozygous LoFs
- 2909
- Defined
- 124695
- p
- 0.0118
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.255 | 597 | 615 | 0.971 | 0.0000369 | 7011 |
| Missense (PolyPhen) | 179 | 178.93 | 1.0004 | 2142 | ||
| Synonymous | -0.00639 | 265 | 265 | 1.00 | 0.0000159 | 2209 |
| Loss of Function | -0.0212 | 50 | 49.8 | 1.00 | 0.00000247 | 532 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0035 | 0.0034 | notable |
| Latino/Admixed American | 0.0048 | 0.0048 | notable |
| Ashkenazi Jewish | 0.017 | 0.017 | notable |
| East Asian | 0.0053 | 0.0051 | notable |
| Finnish | 0.017 | 0.017 | notable |
| European (Non-Finnish) | 0.017 | 0.016 | notable |
| South Asian | 0.0058 | 0.0058 | notable |
| Other | 0.013 | 0.013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. Synthesizes preferentially dimers of 2'-5'- oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNase L) leading to its dimerization and subsequent activation. Activation of RNase L leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. Displays antiviral activity against Chikungunya virus (CHIKV), Dengue virus, Sindbis virus (SINV) and Semliki forest virus (SFV). {ECO:0000269|PubMed:19056102, ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:9880533}.;
Intolerance Scores
- LoFtool
- 0.974
- RVIS EVS
- -0.26
- RVIS percentile EVS
- 34.98
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.317
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |