OAS2 Gene: 2'-5'-Oligoadenylate Synthetase 2
A key antiviral enzyme involved in innate immunity, RNA degradation, and interferon response, with implications in viral infections and cancer.
Gene Information Card
| Symbol | OAS2 |
|---|---|
| Full Name | 2'-5'-oligoadenylate synthetase 2 |
| Gene Type | protein coding |
| Chromosomal Location | 12q24.13 |
| NCBI Gene ID | 4939 ncbi.nlm.nih.gov/gene/4939 |
| Ensembl ID | ENSG00000111335 |
| UniProt ID | P29728 |
| OMIM ID | 603350 |
| HGNC ID | 8087 |
| Aliases | 2'-5'-OAS, 2-5A synthetase 2, p69 OAS, p71 OAS |
Description
The OAS2 gene encodes 2'-5'-oligoadenylate synthetase 2, a key enzyme in the innate immune response against viral infections. It is an interferon-induced protein that synthesizes 2'-5'-linked oligoadenylates (2-5A) from ATP upon binding to double-stranded RNA (dsRNA), a viral replication intermediate. The produced 2-5A molecules activate latent RNase L, leading to the degradation of viral and cellular RNA, thereby inhibiting viral replication. OAS2 is part of the OAS/RNase L pathway, a critical antiviral defense mechanism. The gene produces multiple isoforms through alternative splicing, which have different subcellular localizations and functions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Viral Infections (e.g., Hepatitis C, West Nile Virus) | OAS2 is an interferon-stimulated gene (ISG) that restricts viral replication. Polymorphisms and differential expression of OAS2 are associated with susceptibility and outcome of various viral infections. The encoded protein activates RNase L to degrade viral RNA. | Multiple studies have linked OAS2 variants to altered susceptibility to viral infections. For example, specific SNPs are associated with Hepatitis C virus clearance and West Nile virus neuroinvasive disease (PubMed). |
| Cancer (e.g., Breast, Colorectal) | OAS2 expression is often dysregulated in tumors. Its role in RNA degradation and apoptosis can influence tumor progression. It may act as a tumor suppressor by promoting apoptosis in response to dsRNA, but its expression can also be part of the tumor microenvironment's inflammatory response. | Gene expression profiling and clinical studies show altered OAS2 expression in various cancers. For instance, high OAS2 expression is associated with better prognosis in some cancers, while in others, it is part of an interferon-related gene signature (COSMIC, PubMed). |
| Autoimmune Diseases (e.g., Systemic Lupus Erythematosus) | OAS2 is part of the interferon signature often observed in autoimmune diseases. Chronic activation of the OAS/RNase L pathway may contribute to inflammation and tissue damage. | Elevated expression of OAS2 and other ISGs is a hallmark of SLE and is used as a biomarker for disease activity (PubMed). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 12.4 | Medium |
| Spleen | 11.8 | Medium |
| Liver | 10.5 | Medium |
| Small Intestine | 9.2 | Low |
| Whole Blood | 8.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (Lung Carcinoma) | 15.2 | High expression; inducible by interferon. |
| HepG2 (Liver Carcinoma) | 12.8 | Moderate expression; inducible by interferon. |
| MCF7 (Breast Carcinoma) | 6.5 | Low basal expression; inducible by interferon. |
| K562 (Leukemia) | 4.1 | Low expression. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| rs1293762 (Intronic Variant) | SNP | ~30% (Global) | Associated with altered OAS2 expression and differential susceptibility to viral infections like Hepatitis C. |
| rs2285934 (Intronic Variant) | SNP | ~25% (Global) | Linked to changes in OAS2 activity and may influence the severity of viral infections. |
| Missense Variants (e.g., p.Arg462Gln) | Missense | Rare (<1%) | May affect enzyme catalytic activity or protein stability, potentially altering the antiviral response. |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in OAS2 are rare but would impair the synthesis of 2-5A, leading to a reduced ability to activate RNase L. This would result in a diminished antiviral response, increasing susceptibility to viral infections.
Gain of Function (GOF)
Gain-of-function mutations are not well-documented for OAS2. However, overexpression or increased activity could lead to excessive RNA degradation and apoptosis, potentially contributing to tissue damage or autoimmune phenotypes.
Dominant Negative (DN)
Dominant-negative effects are theoretically possible if a mutant OAS2 protein can dimerize with the wild-type protein and inhibit its function. However, specific dominant-negative mutations have not been clearly characterized in OAS2.
View complete mutation data：
Gene Ontology (GO)
| • 2'-5'-oligoadenylate synthetase activity | • double-stranded RNA binding |
| • ATP binding | • metal ion binding |
| • nucleotidyltransferase activity | • interferon-gamma-mediated signaling pathway |
| • defense response to virus | • innate immune response |
| • apoptotic process | • RNA catabolic process |
Pathways
• OAS/RNase L pathway
• Innate Immune System
• Interferon Signaling
• Antiviral mechanism by IFN-stimulated genes
Protein Summary
The OAS2 protein is a member of the 2'-5'-oligoadenylate synthetase family. It is a 69-71 kDa protein that exists in multiple isoforms due to alternative splicing. The protein is primarily localized in the cytoplasm, where it binds to double-stranded RNA (dsRNA) via its C-terminal domain. Upon dsRNA binding, it catalyzes the polymerization of ATP into 2'-5'-linked oligoadenylates (2-5A). These 2-5A molecules act as second messengers that bind to and activate latent RNase L. Activated RNase L then degrades both viral and cellular RNA, thereby inhibiting protein synthesis and viral replication. OAS2 is a critical component of the innate immune response and is strongly induced by type I interferons.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| OAS2 Knockout HEK293 Cell Line | EDJ-KQ4597 | Human | 4939 | Details Get a Quote |
| OAS2 Knockout HeLa Cell Line | EDJ-KQ54036 | Human | 4939 | Details Get a Quote |
| OAS2 Knockout A-549 Cell Line | EDJ-KQ62524 | Human | 4939 | Details Get a Quote |
| OAS2 Knockout HCT 116 Cell Line | EDJ-KQ70995 | Human | 4939 | Details Get a Quote |
