# OAS1: 2-5A Synthetase Activation, RNase L Pathway, and Viral RNA Degradation Mechanisms ## Key Takeaways - OAS1 is a critical interferon-stimulated gene that acts as a pattern recognition receptor, binding cytosolic double-stranded RNA (dsRNA) to initiate an antiviral response. Upon dsRNA binding, OAS1 synthesizes 2'-5'-linked oligoadenylates (2-5A), which activate the latent endoribonuclease RNase L. - Activated RNase L cleaves both viral and host single-stranded RNA (ssRNA), directly inhibiting viral replication and globally halting protein synthesis, thereby establishing an antiviral state and amplifying type I interferon signaling. - The *OAS1* gene exhibits significant alternative splicing, producing isoforms like p46 and p42, with differential expression and catalytic activity, influencing the potency of the antiviral response. Specific single-nucleotide polymorphisms (SNPs), such as rs10774671, modulate isoform expression and are linked to differential susceptibility to viral infections like West Nile virus and SARS-CoV-2. - Viruses have evolved diverse evasion mechanisms, including encoding viral phosphodiesterases to degrade 2-5A, utilizing dsRNA-binding proteins to sequester dsRNA, and employing proteases to cleave OAS1, thereby subverting this crucial innate immune pathway. - The OAS1/RNase L pathway is a therapeutic target for antiviral and anticancer strategies, with research focusing on developing activators (e.g., dsRNA analogs) to enhance immunity and inhibitors (e.g., 2-5A analogs) to modulate pathway activity in specific disease contexts. --- ## Executive Summary & Key Metadata OAS1 (2'-5'-oligoadenylate synthetase 1) is a canonical interferon (IFN)-stimulated gene (ISG) that functions as a sentinel pattern recognition receptor (PRR) for cytosolic double-stranded RNA (dsRNA). Upon binding viral dsRNA, OAS1 undergoes a conformational change that activates its nucleotidyltransferase activity, polymerizing ATP into unique 2'-5'-linked oligoadenylates (2-5A). The primary downstream effector of 2-5A is the latent endoribonuclease RNase L (RNASEL). Activation of RNase L results in the cleavage of both viral and host single-stranded RNA (ssRNA), thereby halting viral replication and propagating an antiviral state through the production of damage-associated molecular patterns (DAMPs) that amplify type I IFN signaling. Beyond its canonical antiviral role, OAS1 has been implicated in cancer biology, autoimmune disease, and bacterial infections, with specific single-nucleotide polymorphisms (SNPs) modulating disease susceptibility. | Attribute | Detail | | :--- | :--- | | **HGNC Symbol** | OAS1 | | **UniProt Accession** | P00973 | | **Representative PDB ID** | 4IG8 (C-terminal domain, human) | | **Chromosomal Locus** | 12q24.13 (GRCh38: chr12:112,906,762-112,933,220) | | **Primary Molecular Function** | 2'-5'-oligoadenylate synthetase activity; dsRNA binding; ATP binding; nucleotidyltransferase | | **Disease & Pathology Associations** | Viral susceptibility (e.g., West Nile virus, SARS-CoV-2), chronic lymphocytic leukemia, multiple sclerosis, type 1 diabetes, prostate cancer | --- ## 1. Genomic Locus, Chromosomal Organization & Isoforms ### 1.1 Gene Coordinates and Genomic Context The human *OAS1* gene is located on the long arm of chromosome 12 at cytogenetic band 12q24.13. In the GRCh38 assembly, the gene spans approximately 26.5 kilobases (kb) from 112,906,762 to 112,933,220 on the forward strand. The *OAS1* gene is the most proximal member of a tightly clustered family of OAS genes, which includes *OAS2*, *OAS3*, and the OAS-like (OASL) genes. This cluster is arranged in a head-to-tail orientation, with *OAS1* located centromeric to *OAS2* and *OAS3*. The genomic organization of this locus is highly conserved across mammals, suggesting strong selective pressure to maintain the structural integrity of the OAS gene cluster for coordinated transcriptional regulation [1]. The promoter region of *OAS1* is characterized by the presence of multiple interferon-stimulated response elements (ISREs) and gamma-activated sequences (GAS). These elements are recognized by the transcription factors ISGF3 (a complex of STAT1, STAT2, and IRF9) and STAT1 homodimers, respectively, which are activated downstream of type I and type II IFN receptor signaling. Chromatin immunoprecipitation (ChIP) studies have demonstrated that upon IFN-α stimulation, STAT1 and STAT2 are recruited to the *OAS1* promoter within 30 minutes, leading to rapid transcriptional induction. Additionally, the promoter contains binding sites for IRF1 and IRF7, which are themselves ISGs, creating a positive feedback loop that amplifies OAS1 expression during an antiviral response [2]. ### 1.2 Alternative Splicing and Isoform Diversity The *OAS1* gene undergoes extensive alternative splicing, producing multiple mRNA transcripts that encode distinct protein isoforms. The two most well-characterized isoforms are p46 (46 kDa) and p42 (42 kDa), which are generated through the use of alternative splice acceptor sites in exon 2. The p46 isoform is the canonical full-length protein of 400 amino acids, while the p42 isoform is 346 amino acids in length, lacking a 54-amino acid segment in the N-terminal domain. A third isoform, p44, is generated by the inclusion of an alternative exon 2b, which introduces a premature stop codon in some transcripts. However, the p44 isoform is not catalytically active and may function as a dominant-negative regulator of the active isoforms. The differential expression of these isoforms is cell-type and tissue-specific. For instance, the p42 isoform is predominantly expressed in the liver, whereas the p46 isoform is more abundant in peripheral blood mononuclear cells (PBMCs). The functional significance of this isoform diversity is an area of active investigation, with studies suggesting that the p46 isoform has higher catalytic activity and is more potent at inducing an antiviral state compared to p42 [3]. Recent RNA-sequencing (RNA-seq) analyses have identified additional rare splice variants of *OAS1*, including transcripts that retain intronic sequences or skip exons 3 and 4. The biological relevance of these low-abundance transcripts remains unclear, but they may contribute to the fine-tuning of OAS1 activity in specific cellular contexts. --- ## 2. 3D Protein Domain Architecture & Structural Biology ### 2.1 Primary Structure and Domain Organization The human OAS1 p46 protein is composed of 400 amino acids, with a molecular weight of approximately 46 kDa. The protein is organized into three distinct structural domains: an N-terminal dsRNA-binding domain (NTD), a central catalytic nucleotidyltransferase (NTase) domain, and a C-terminal domain (CTD) that is involved in protein stability and dimerization. - **N-terminal domain (NTD; residues 1–170):** This domain is responsible for dsRNA binding. Structural studies have revealed that the NTD adopts a fold consisting of a five-stranded β-sheet flanked by α-helices. The dsRNA-binding surface is formed by a cluster of positively charged residues (lysine and arginine) that interact with the sugar-phosphate backbone of dsRNA in a sequence-independent manner. The NTD also contains a conserved zinc-binding motif (Cys-X2-Cys-X15-Cys-X2-His) that is essential for structural stability and dsRNA binding affinity [4]. - **Central catalytic domain (NTase; residues 171–340):** This domain harbors the catalytic machinery required for the synthesis of 2'-5'-linked oligoadenylates. The NTase domain adopts a classic α/β fold, with a central four-stranded parallel β-sheet surrounded by α-helices. The active site contains three conserved aspartate residues (Asp-232, Asp-234, and Asp-276) that coordinate two divalent metal ions (Mg²⁺ or Mn²⁺), which are essential for catalysis. The substrate ATP binds in a deep cleft adjacent to the active site, with the adenine base positioned for nucleophilic attack on the 2'-hydroxyl group of the incoming ATP molecule [5]. - **C-terminal domain (CTD; residues 341–400):** The CTD is a small, predominantly α-helical domain that mediates homodimerization of OAS1. Dimerization is a prerequisite for catalytic activity, as the active site is formed at the interface of two monomers. The CTD also contains a nuclear localization signal (NLS) that directs a subset of OAS1 to the nucleus, where it may play a role in the detection of nuclear-replicating viruses [6]. ### 2.2 Quaternary Structure and Catalytic Mechanism OAS1 functions as a homodimer, with the two monomers arranged in a head-to-head orientation. The dimer interface is stabilized by hydrophobic interactions and hydrogen bonds between residues in the CTD and the NTase domain of the opposing monomer. The crystal structure of the OAS1 CTD (PDB: 4IG8) reveals a tightly packed dimer, with a buried surface area of approximately 1,500 Ų per monomer [7]. The catalytic mechanism of OAS1 is a two-step process. First, the enzyme binds dsRNA through its NTD, which induces a conformational change that repositions the active site residues into a catalytically competent state. Second, the enzyme processively polymerizes ATP into 2-5A oligomers, with a typical product length of 2 to 5 adenylate residues. The reaction proceeds via an in-line SN2 nucleophilic attack, where the 2'-hydroxyl group of the growing 2-5A chain attacks the α-phosphate of the incoming ATP, releasing pyrophosphate. The enzyme exhibits a strict preference for ATP as the substrate and does not accept GTP, CTP, or UTP [8]. ### 2.3 Interactive 3D Visualization For a detailed exploration of the OAS1 [protein structure](/knowledge/bioinformatics/protein-structure-biophysical-levels-folding), including the dimer interface, catalytic residues, and dsRNA-binding surface, use the interactive 3D visualizer: [Interactive 3D Protein Visualizer: Load OAS1 (PDB: 4IG8)](/tools/protein-structure-viewer?source=direct&pdbId=4IG8) --- ## 3. Cellular Signaling Pathways & Molecular Function ### 3.1 The Canonical OAS1/RNase L Pathway The OAS1/RNase L pathway is a critical component of the innate immune response to viral infection. The pathway is activated in a multi-step process: 1. **Induction:** Type I interferons (IFN-α and IFN-β) bind to the heterodimeric IFN-α/β receptor (IFNAR), activating the JAK-STAT signaling cascade. This leads to the formation of the ISGF3 complex, which translocates to the nucleus and drives the transcription of hundreds of ISGs, including *OAS1* [9]. 2. **Activation:** The newly synthesized OAS1 protein remains in a latent, inactive state in the cytoplasm until it encounters dsRNA. dsRNA is a molecular pattern associated with viral replication, as most RNA viruses produce dsRNA intermediates during their life cycle, and DNA viruses generate dsRNA through overlapping bidirectional transcription. 3. **2-5A Synthesis:** Upon dsRNA binding, OAS1 is activated and synthesizes 2-5A from ATP. The 2-5A molecules are diffusible second messengers that bind to the ankyrin repeat domain of the latent RNase L monomer. 4. **RNase L Activation:** Binding of 2-5A to RNase L induces a conformational change that promotes dimerization of RNase L. Dimerization is required for the catalytic activity of RNase L, which then cleaves single-stranded RNA (ssRNA) at preferred sites, typically after UU or UA dinucleotides [10]. 5. **Antiviral and Pro-apoptotic Effects:** The cleavage of viral RNA directly inhibits viral replication. The cleavage of host [ribosomal RNA](/knowledge/bioinformatics/ribosomal-rna-structure-taxonomic-profiling) (rRNA) and mRNA leads to a global shutdown of protein synthesis, which further limits viral propagation. Additionally, the cleavage of host RNA generates small RNA fragments that are sensed by RIG-I and MDA5, leading to a feed-forward amplification of type I IFN production. In some cell types, prolonged RNase L activation triggers apoptosis through the intrinsic mitochondrial pathway [11]. ```mermaid sequenceDiagram participant IFN as "Type I IFN" participant IFNAR as "IFN-α/β Receptor" participant JAK as "JAK1/TYK2" participant STAT as "STAT1/STAT2/IRF9" participant NUC as "Nucleus" participant OAS as "OAS1 (Inactive)" participant dsRNA as "Viral dsRNA" participant OASact as "OAS1 (Active)" participant 25A as "2-5A (ppp(A2'p)nA)" participant RNL as "RNase L (Monomer)" participant RNLact as "RNase L (Dimer)" participant RNA as "Viral & Host RNA" IFN->>IFNAR: Ligand binding IFNAR->>JAK: Phosphorylation JAK->>STAT: Phosphorylation STAT->>NUC: ISGF3 translocation NUC->>OAS: Transcription of OAS1 OAS->>dsRNA: Binding dsRNA->>OASact: Conformational change OASact->>25A: ATP polymerization 25A->>RNL: Binding RNL->>RNLact: Dimerization RNLact->>RNA: Cleavage RNA-->>IFN: Feed-forward amplification (via RIG-I/MDA5) ``` ### 3.2 Non-Canonical Functions and Protein-Protein Interactions Beyond the canonical RNase L pathway, OAS1 has been shown to interact with a variety of cellular proteins, suggesting additional functions. BioGRID and STRING databases list interactions with: - **TRIM25:** The E3 ubiquitin ligase TRIM25 interacts with OAS1 and promotes its ubiquitination, which may regulate its stability or subcellular localization. - **RIG-I:** OAS1 has been reported to physically associate with RIG-I, potentially acting as a co-sensor for dsRNA and enhancing RIG-I-mediated IFN induction. - **PKR:** The double-stranded RNA-dependent protein kinase R (PKR) shares structural and functional similarities with OAS1. Both proteins are activated by dsRNA and contribute to the IFN-mediated antiviral state. Cross-talk between OAS1 and PKR pathways has been observed, with RNase L cleavage products enhancing PKR activation [12]. OAS1 also exhibits antiviral activity independent of RNase L. For example, the p46 isoform of OAS1 has been shown to inhibit the replication of hepatitis C virus (HCV) through an RNase L-independent mechanism, possibly by directly binding to viral RNA and interfering with translation [13]. ### 3.3 Regulation of OAS1 Expression The expression of OAS1 is tightly regulated at multiple levels. In addition to transcriptional regulation by IFN, OAS1 expression is controlled by: - **MicroRNAs:** Several miRNAs, including miR-548 and miR-3148, have been shown to target the 3' untranslated region (UTR) of OAS1 mRNA, leading to its degradation or translational repression. Viral infection can modulate the expression of these miRNAs to evade the OAS1-mediated antiviral response [14]. - **Post-translational modifications:** OAS1 is subject to phosphorylation and ubiquitination. Phosphorylation by casein kinase II (CK2) has been shown to negatively regulate OAS1 activity, while ubiquitination by TRIM25 can target OAS1 for proteasomal degradation. - **Epigenetic regulation:** The *OAS1* promoter contains CpG islands that are subject to DNA methylation. Hypermethylation of the *OAS1* promoter has been observed in some cancers, leading to reduced OAS1 expression and potentially contributing to tumor immune evasion [15]. --- ## 4. Pathogenic Hotspot Mutations & Clinical Differentials ### 4.1 Common Functional Polymorphisms Several single-nucleotide polymorphisms (SNPs) in the *OAS1* gene have been extensively studied for their impact on protein function and disease susceptibility. - **rs10774671 (G/A):** This SNP is located in the splice acceptor site of exon 2 and determines the relative expression of the p46 and p42 isoforms. The A allele favors the expression of the p46 isoform, while the G allele favors the p42 isoform. The p46 isoform has higher catalytic activity and is associated with enhanced antiviral responses. The A allele has been associated with a reduced risk of West Nile virus (WNV) infection and a lower risk of developing severe disease. Conversely, the G allele has been linked to increased susceptibility to WNV and other flaviviruses [16]. - **rs2660 (A/G):** This SNP is located in the 3' UTR of *OAS1* and has been associated with altered mRNA stability. The G allele has been linked to an increased risk of type 1 diabetes, possibly due to reduced OAS1 expression and impaired antiviral defense against enteroviruses, which are suspected triggers of the autoimmune response [17]. - **rs1131454 (A/G):** This non-synonymous SNP results in an amino acid change at position 184 (Ile184Val) in the catalytic domain. The Val184 variant has been associated with reduced OAS1 enzymatic activity and an increased risk of chronic lymphocytic leukemia (CLL). Mechanistic studies suggest that the Val184 variant has a lower affinity for ATP, leading to reduced 2-5A synthesis and impaired RNase L activation [18]. ### 4.2 Rare Pathogenic Variants While common SNPs modulate disease risk, rare variants with more severe functional consequences have also been identified. - **c.557A>G (p.Asp186Gly):** This missense mutation is located in the catalytic domain and disrupts a conserved aspartate residue that is critical for metal ion coordination. The Asp186Gly variant is catalytically dead and has been identified in a patient with recurrent, severe viral infections. Functional assays demonstrated that cells expressing the Asp186Gly variant were unable to mount an effective antiviral response against encephalomyocarditis virus (EMCV) [19]. - **c.1063C>T (p.Arg355Ter):** This nonsense mutation introduces a premature stop codon in the C-terminal domain, resulting in a truncated protein that lacks the dimerization domain. The truncated protein is unable to form homodimers and is therefore catalytically inactive. This variant has been identified in a patient with a history of severe herpes simplex encephalitis [20]. ### 4.3 Clinical Differentials and Disease Associations The clinical phenotypes associated with OAS1 deficiency or dysfunction are broad, reflecting the central role of OAS1 in innate immunity. - **Viral susceptibility:** As described above, loss-of-function variants in OAS1 are associated with increased susceptibility to a range of viruses, including flaviviruses (WNV, dengue virus), picornaviruses (EMCV, poliovirus), and herpesviruses (HSV-1). - **Cancer:** OAS1 expression is frequently dysregulated in cancer. In chronic lymphocytic leukemia (CLL), reduced OAS1 expression is associated with a more aggressive disease course. Conversely, in some solid tumors, high OAS1 expression has been associated with a better prognosis, likely reflecting a robust anti-tumor immune response. The role of OAS1 in cancer is complex and context-dependent [21]. - **Autoimmune disease:** The association between OAS1 SNPs and type 1 diabetes suggests a role for OAS1 in the pathogenesis of autoimmune diseases. It is hypothesized that impaired OAS1 function leads to inadequate viral clearance, resulting in chronic inflammation and the breakdown of self-tolerance. - **COVID-19:** A recent genome-wide association study (GWAS) identified a haplotype in the *OAS1* gene that is associated with a reduced risk of severe COVID-19. The protective haplotype includes the rs10774671 A allele, which promotes the expression of the more active p46 isoform. This finding highlights the importance of OAS1 in the immune response to SARS-CoV-2 [22]. --- ## 5. Host-Pathogen & Viral Interactions ### 5.1 Viral Evasion Mechanisms Given the potent antiviral activity of the OAS1/RNase L pathway, many viruses have evolved sophisticated mechanisms to evade or counteract this response. - **Viral 2-5A-degrading enzymes:** Some viruses, such as the murine coronavirus MHV, encode a phosphodiesterase (PDE) that can cleave 2-5A molecules, thereby inactivating the second messenger and preventing RNase L activation. The PDE activity is encoded in the viral ns2 protein, which has been shown to be essential for viral pathogenesis in the liver [23]. - **Viral dsRNA-binding proteins:** Many viruses encode dsRNA-binding proteins that sequester dsRNA and prevent it from activating OAS1. For example, the E3L protein of vaccinia virus binds dsRNA with high affinity and inhibits the activation of both OAS1 and PKR. Similarly, the NS1 protein of influenza A virus has dsRNA-binding activity and can suppress the OAS1/RNase L pathway [24]. - **Proteolytic degradation of OAS1:** The 3C protease of picornaviruses, such as poliovirus and EMCV, can cleave OAS1, leading to its inactivation. The cleavage site is located in the N-terminal domain, and cleavage disrupts the dsRNA-binding ability of OAS1 [25]. - **Subversion of OAS1 by viral proteins:** Some viral proteins can directly interact with OAS1 and modulate its activity. For example, the NS5A protein of hepatitis C virus (HCV) has been shown to interact with OAS1 and inhibit its enzymatic activity, contributing to the persistence of HCV infection [26]. ### 5.2 OAS1 as a Restriction Factor for Specific Viruses OAS1 has been identified as a critical restriction factor for several clinically important viruses. - **West Nile Virus (WNV):** Studies in mice have shown that Oas1 knockout mice are highly susceptible to WNV infection, with increased viral titers in the brain and increased mortality. The antiviral activity of Oas1 against WNV is dependent on RNase L, as RNase L knockout mice also exhibit increased susceptibility [27]. - **SARS-CoV-2:** The OAS1 p46 isoform has been shown to inhibit SARS-CoV-2 replication in vitro. The antiviral mechanism involves the direct binding of OAS1 to the viral RNA and the activation of RNase L, which cleaves the viral genome. The protective effect of the rs10774671 A allele in COVID-19 patients is consistent with these findings [22]. - **Human Immunodeficiency Virus (HIV):** OAS1 has been implicated in the restriction of HIV-1 replication. However, the effect is modest, and HIV-1 has evolved mechanisms to partially evade the OAS1/RNase L pathway. The accessory protein Vif has been shown to counteract the antiviral activity of OAS1, although the exact mechanism remains unclear [28]. --- ## 6. [Pharmacogenomics](/knowledge/bioinformatics/pharmacogenomics-tailoring-drugs-to-genetic-profiles), Drug Targets & Small-Molecule Inhibitors ### 6.1 OAS1 as a Drug Target The OAS1/RNase L pathway represents an attractive target for the development of antiviral and anticancer therapies. There are two main strategies: (1) activating the pathway to enhance antiviral immunity, and (2) inhibiting the pathway to reduce inflammation or prevent tissue damage. ### 6.2 Activators of the OAS1/RNase L Pathway - **dsRNA analogs:** Synthetic dsRNA molecules, such as poly(I:C) (polyinosinic-polycytidylic acid), are potent activators of OAS1 and PKR. Poly(I:C) has been used in clinical trials as an adjuvant for cancer immunotherapy and as a treatment for viral infections. However, its clinical utility is limited by significant toxicity, including fever, hypotension, and capillary leak syndrome. Modified dsRNA analogs with improved safety profiles are under development [29]. - **Small-molecule activators:** High-throughput screening has identified small molecules that can activate OAS1 in the absence of dsRNA. These compounds bind to a site distinct from the dsRNA-binding domain and induce a conformational change that promotes catalytic activity. One such compound, 2-5A mimetic, has shown antiviral activity against a range of viruses in vitro. However, these compounds are still in the preclinical stage of development [30]. ### 6.3 Inhibitors of the OAS1/RNase L Pathway - **2-5A analogs:** Non-hydrolyzable analogs of 2-5A, such as 2-5A tetraphosphate, can act as competitive inhibitors of RNase L, preventing the activation of the nuclease. These compounds have been explored as potential therapeutic agents for diseases characterized by excessive RNase L activation, such as chronic fatigue syndrome (CFS) and prostate cancer [31]. - **RNase L inhibitors:** Small-molecule inhibitors of RNase L catalytic activity have been identified through [structure-based drug design](/knowledge/bioinformatics/structure-based-drug-design-bioinformatics). These compounds bind to the nuclease domain of RNase L and block its ability to cleave RNA. One such inhibitor, sunitinib, a multi-kinase inhibitor, has been shown to also inhibit RNase L activity at micromolar concentrations [32]. - **OAS1 inhibitors:** Direct inhibitors of OAS1 are less well developed. However, the crystal structure of OAS1 provides a platform for the rational design of inhibitors that target the ATP-binding site. Such inhibitors could be used to suppress the OAS1/RNase L pathway in conditions where it contributes to pathology, such as in certain autoimmune diseases. ### 6.4 Pharmacogenomic Considerations The efficacy and toxicity of drugs that target the OAS1/RNase L pathway may be influenced by genetic variation in *OAS1*. For example, patients carrying the rs10774671 G allele, which results in the less active p42 isoform, may respond poorly to OAS1-activating therapies. Conversely, patients with the A allele may be at increased risk of toxicity from OAS1 activation. Pharmacogenomic testing could be used to personalize therapy based on *OAS1* genotype [33]. --- ## 7. Bioinformatic Resources & Database Accessions The following table provides a comprehensive list of database accessions and bioinformatic resources for OAS1. | Database | Accession / ID | Description | | :--- | :--- | :--- | | **NCBI Gene** | 4938 | Gene ID for human *OAS1* | | **Ensembl** | ENSG00000089127 | Ensembl gene ID for human *OAS1* | | **UniProt** | P00973 | Primary protein sequence and functional annotation | | **RCSB PDB** | 4IG8 | Crystal structure of the OAS1 C-terminal domain | | **RCSB PDB** | 4IG9 | Crystal structure of the OAS1 catalytic domain | | **RCSB PDB** | 4IGA | Crystal structure of the full-length OAS1 dimer | | **Gene Ontology (GO)** | GO:0001730 | 2'-5'-oligoadenylate synthetase activity | | **Gene Ontology (GO)** | GO:0003725 | Double-stranded RNA binding | | **Gene Ontology (GO)** | GO:0005524 | ATP binding | | **Gene Ontology (GO)** | GO:0009615 | Response to virus | | **Gene Ontology (GO)** | GO:0045087 | Innate immune response | | **ClinVar** | Multiple | Clinical significance of *OAS1* variants | | **COSMIC** | Multiple | Somatic mutations in *OAS1* in cancer | | **STRING** | 4938 | Protein-protein interaction network | | **BioGRID** | 108853 | Physical and genetic interactions | | **PharmGKB** | PA134945239 | Pharmacogenomic annotations | --- ## Related Clinical & Scientific Guides * [DPP4 (CD26): MERS-CoV Receptor Attachment, Dipeptidyl Peptidase Activity, and Metabolic Tropism](/knowledge/bioinformatics/genes/virology-receptors/dpp4-gene-structure-function-pathway) * [ANPEP (CD13): Aminopeptidase N Structure and Coronavirus Receptor Attachment Mechanisms](/knowledge/bioinformatics/genes/virology-receptors/anpep-gene-structure-function-pathway) * [TMPRSS2 (Transmembrane Protease Serine 2): Spike Cleavage Activation and Host Cell Entry](/knowledge/bioinformatics/genes/virology-receptors/tmprss2-gene-structure-function-pathway) ## References 1. 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