OAS1

Summary

OAS1 (2’-5’-oligoadenylate synthetase 1, HGNC:8086) is a protein-coding gene on chromosome 12q24.13, encoding 2’-5’-oligoadenylate synthase 1 (P00973). Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response.

This interferon-induced gene encodes a protein that synthesizes 2’,5’-oligoadenylates (2-5As). This protein plays a key role in innate cellular antiviral response, and has been implicated in other cellular processes like cell growth and apoptosis. Alternative splicing results in multiple transcript variants with different enzymatic activities. Polymorphisms in this gene have been associated with susceptibility to viral infection, including SARS-CoV-2, and diabetes mellitus, type 1. This gene is located in a cluster of related genes on chromosome 12.

Source: NCBI Gene 4938 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pulmonary alveolar proteinosis with hypogammaglobulinemia (Strong, GenCC)
• GWAS associations: 8
• Clinical variants (ClinVar): 344 total — 1 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 11
• MANE Select transcript: NM_016816

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8086
Approved symbol	OAS1
Name	2’-5’-oligoadenylate synthetase 1
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Aliases	OIASI, IFI-4
Ensembl gene	ENSG00000089127
Ensembl biotype	protein_coding
OMIM	164350
Entrez	4938

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 22 protein_coding, 5 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000202917, ENST00000445409, ENST00000452357, ENST00000540589, ENST00000549820, ENST00000550689, ENST00000550883, ENST00000551241, ENST00000552526, ENST00000553152, ENST00000553185, ENST00000675868, ENST00000679413, ENST00000679467, ENST00000679494, ENST00000679767, ENST00000679841, ENST00000679971, ENST00000679987, ENST00000680189, ENST00000680455, ENST00000680522, ENST00000680659, ENST00000680919, ENST00000680934, ENST00000681194, ENST00000681228, ENST00000681436, ENST00000681466, ENST00000681505, ENST00000681700, ENST00000681831, ENST00000681934

RefSeq mRNA: 15 — MANE Select: NM_016816 NM_001032409, NM_001320151, NM_001406020, NM_001406021, NM_001406022, NM_001406023, NM_001406024, NM_001406025, NM_001406026, NM_001406027, NM_001406029, NM_001406030, NM_001412228, NM_002534, NM_016816

CCDS: CCDS31905, CCDS41838, CCDS44980, CCDS81742, CCDS91752, CCDS91755

Canonical transcript exons

ENST00000202917 — 6 exons

Exon	Start	End
ENSE00000755368	112911051	112911235
ENSE00000755369	112916509	112916738
ENSE00001000320	112917547	112917700
ENSE00001104120	112919389	112919903
ENSE00002324997	112906962	112907219
ENSE00003541038	112908536	112908824

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.7802 / max 1211.8814, expressed in 1138 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128108	15.4255	1077
128109	8.6889	747
128110	0.3898	139
128107	0.2645	138
128114	0.0115	4

Top tissues by expression

286 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.34	gold quality
leukocyte	CL:0000738	97.92	gold quality
mononuclear cell	CL:0000842	97.92	gold quality
mucosa of transverse colon	UBERON:0004991	97.64	gold quality
granulocyte	CL:0000094	97.60	gold quality
rectum	UBERON:0001052	95.63	gold quality
esophagus mucosa	UBERON:0002469	94.30	gold quality
ileal mucosa	UBERON:0000331	93.82	gold quality
lower esophagus mucosa	UBERON:0035834	93.30	gold quality
spleen	UBERON:0002106	93.28	gold quality
gall bladder	UBERON:0002110	92.54	gold quality
nasal cavity epithelium	UBERON:0005384	92.04	gold quality
right lobe of liver	UBERON:0001114	91.46	gold quality
blood	UBERON:0000178	91.37	gold quality
transverse colon	UBERON:0001157	91.33	gold quality
colonic mucosa	UBERON:0000317	91.09	gold quality
duodenum	UBERON:0002114	90.67	gold quality
lymph node	UBERON:0000029	90.27	gold quality
esophagus squamous epithelium	UBERON:0006920	89.96	gold quality
vermiform appendix	UBERON:0001154	89.92	gold quality
epithelium of esophagus	UBERON:0001976	89.82	gold quality
jejunal mucosa	UBERON:0000399	89.58	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.58	gold quality
mucosa of sigmoid colon	UBERON:0004993	89.19	gold quality
small intestine	UBERON:0002108	89.17	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.99	gold quality
pancreatic ductal cell	CL:0002079	88.53	silver quality
right lung	UBERON:0002167	88.50	gold quality
apex of heart	UBERON:0002098	88.45	gold quality
decidua	UBERON:0002450	88.45	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	14.22
E-HCAD-13	yes	12.03
E-MTAB-7606	no	79.93
E-GEOD-83139	no	3.71

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CUX1, IFI16, IRF9, SATB1, SP1, SP3, SPI1, STAT1, STAT2, STAT3, ZNF148

miRNA regulators (miRDB)

29 targeting OAS1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-3616-5P	99.55	67.02	989
HSA-MIR-573	99.55	67.44	955
HSA-MIR-4316	99.37	65.75	1360
HSA-MIR-7974	99.24	65.48	1137
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-6873-5P	98.45	66.14	1417
HSA-MIR-4518	98.12	66.82	1030
HSA-MIR-1266-5P	97.71	66.92	1052
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-6815-5P	96.05	65.55	662
HSA-MIR-6865-5P	96.05	65.58	675
HSA-MIR-7848-3P	95.69	65.00	363
HSA-MIR-6802-5P	94.94	65.95	366
HSA-MIR-764	94.16	64.85	656

Literature-anchored findings (GeneRIF, showing 40)

• role in interferon-gamma inhibition of respiratory syncytial virus infection of human epithelial cells (PMID:11980899)
• identification of the substrate-binding sites (PMID:11986302)
• sequence motifs in OAS1 regulate polyadenylation (PMID:12082089)
• Polymorphisms in the OSA1 gene is associated with outcome of hepatitis C virus infection (PMID:12944978)
• This genetic polymorphism makes OAS1 an excellent candidate for a human gene that influences host susceptibility to viral infection. (PMID:15732009)
• polymorphisms of two interferon-inducible genes OAS-1 and myxovirus resistance-A might affect susceptibility to the disease and progression of severe acute respiratory syndrome at each level (PMID:15766558)
• IL-28A and IL-29 induced mRNA expression of the antiviral proteins 2’,5’-OAS and MxA was abolished by overexpression of SOCS-1 (PMID:15850793)
• OAS1 single nucleotide polymorphisms were significantly increased in diabetic compared with healthy siblings. (PMID:15855350)
• Naturally mutated residues Lys404, Pro500 and Ser471 of E17 isozyme of 2’,5’-oligoadenylate synthetase from a transgenic mouse serve an essential function in maintaining the enzyme activity of the protein. (PMID:15865429)
• single nucleotide polymorphisms (SNPs) identified in OAS exons in hospitalized patients with West Nile Virus infection (PMID:16235172)
• No evidence of association with either type 1 diabetic affcted or unaffected siblings in terms of relative risk. (PMID:16644715)
• Polymorphisms within the OAS1 gene are associated with susceptibility to severe acute respiratory syndrome. (PMID:16824203)
• findings indicate that the OAS1 gene polymorphisms may confer susceptibility to multiple sclerosis or serve as markers of functional variants and suggest that OAS1 activity is involved in the etiology of the disease (PMID:17092260)
• 2’-5’ oligoadenylate synthetase 1 gene polymorphism in associated with hepatitis B susceptibility. (PMID:17963609)
• The pronounced difference in gene regulation between the OAS1 gene agrees with a functional difference between these genes, which must exist as a consequence of the lack of the 2-5A synthetase activity of the OASL protein. (PMID:19203244)
• Data identifies OAS1 single nucleotide polymorphism rs10774671 as a host genetic risk factor for initial infection with West Nile Virus in humans. (PMID:19247438)
• The expression levels of both MX1 and OAS1 in systemic lupus erythematosus patients are up-regulated, and he expression levels of OAS1 genes are associated with SLE disease activity. (PMID:19462904)
• The SNP of OAS-1 at the exon 3 of its coding sequence was associated with progression of disease in Japanese patients with HCV infection. (PMID:19515215)
• Data show that the hepatitis C virus core protein specifically and effectively activates the 2’-5’oligoadenylate synthetase gene promoter. (PMID:19575500)
• mechanism of 2’-5’-oligoadenylate synthetase activation by double stranded RNA was studied. (PMID:19665006)
• SNP rs10774671 of OAS-1 gene benefits patients with chronic HBV infection to achieve spontaneous HBeAg seroconversion. (PMID:19799013)
• OAS1 data suggest that there may be a weak association with type I diabetes for two OAS1 polymorphisms, rs3741981 and rs10774671, in populations of European descent. (PMID:19956105)
• association between gene haplotypes and rubella virus-specific cytokine secretion in children immunized with rubella vaccine (PMID:20079393)
• These findings indicate that the expression of MxA, 2’,5’-OAS and PKR are up-regulate by PI3K-AKT signal pathway, and Raf-MEK-ERK signal pathway has a negative regulatory effect on the expression of MxA and no significant effect on 2’,5’-OAS and PKR. (PMID:20309637)
• A functional OAS1 single nucleotide polymorphism, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity. (PMID:20679634)
• Show a significant association between the functional SNP at exon 7 SAS of OAS1 gene and the viral response to interferon in chronic hepatitis c patients. (PMID:21182542)
• The authors report that expression of human herpesvirus 5 ORF94 protein leads to decreased 2’,5’-oligoadenylate synthetase (OAS) expression in transfected cells with and without interferon stimulation. (PMID:21450824)
• The OAS1 SNP rs2660 AA genotype was associated significantly with prostate cancer, whereas the GG genotype protected against prostate cancer. (PMID:21638280)
• Polymorphisms in OAS1 is associated with multiple sclerosis. (PMID:21735172)
• A single SNP in OAS1 (OR 9.79, p = 0.003) was associated with increased risk for West Nile encephalitis and paralysis (WNE/P). (PMID:21935451)
• Taken together, these data suggest a plausible strategy whereby the adenovirus produces a single RNA transcript capable of inhibiting a variety of members of the innate immune response, including OAS1. (PMID:22709583)
• These results identify OAS1 single nucleotide polymorphism rs2660, rs10774671, and rs3741981 as genetic risk factors for chronic hepatitis C. (PMID:22710942)
• Data show that transfection of ORMDL3 in bronchial epithelial cells induced expression of MMP-9, ADAM-8, CCL-20, IL-8, CXCL-10, CXCL-11, oligoadenylate synthetases (OAS) genes, and selectively activated activating transcription factor 6 (ATF6). (PMID:23011799)
• among the members of the OAS family, OAS1 p46 and OAS3 p100 mediate the RNase L-dependent antiviral activity against HCV (PMID:23196181)
• Findings provide insights into the potential role of OAS1 polymorphisms in respiratory infection. (PMID:23220500)
• Data show that oligoadenylate synthetase 1 (hOAS1) undergoes more than 20,000-fold activation upon double-stranded RNA (dsRNA) binding. (PMID:23319625)
• The results suggest that OAS1-OAS3-OAS2 haplotypes are associated with differential susceptibility to clinical outcomes of dengue infection. (PMID:23337612)
• protein expression is inhibited by hepatitis C virus (PMID:23529855)
• Newly implicated variants (MYL2, C12orf51 and OAS1) were found to be significantly associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes. (PMID:23575436)
• The IFNs inhibit viral infections in part through the 2’,5’-oligoadenylate (2-5A) synthetase (OAS)/RNase L pathway. (PMID:24905202)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
mus_musculus	Oas1c	ENSMUSG00000001166
mus_musculus	Oas1h	ENSMUSG00000001168
mus_musculus	Oas1b	ENSMUSG00000029605
mus_musculus	Oas1d	ENSMUSG00000032623
mus_musculus	Oas1a	ENSMUSG00000052776
mus_musculus	Oas1f	ENSMUSG00000053765
mus_musculus	Oas1g	ENSMUSG00000066861
mus_musculus	Oas1e	ENSMUSG00000066867
rattus_norvegicus	Oas1a	ENSRNOG00000001369
rattus_norvegicus	Oas1d	ENSRNOG00000024462
rattus_norvegicus	Oas1e	ENSRNOG00000031726
rattus_norvegicus	Oas1b	ENSRNOG00000033220
rattus_norvegicus	Oas1h	ENSRNOG00000057769
rattus_norvegicus	Oas1k	ENSRNOG00000062846
rattus_norvegicus	Oas1f	ENSRNOG00000068922

Paralogs (3): OAS3 (ENSG00000111331), OAS2 (ENSG00000111335), OASL (ENSG00000135114)

Protein

Protein identifiers

2’-5’-oligoadenylate synthase 1 — P00973 (reviewed: P00973)

Alternative names: E18/E16, p46/p42 OAS

All UniProt accessions (21): P00973, A0A6Q8PHR1, A0A7P0T854, A0A7P0T879, A0A7P0T8E1, A0A7P0T8F9, A0A7P0T960, A0A7P0T9J4, A0A7P0T9Q4, A0A7P0TAY6, A0A7P0TB35, A0A7P0TBG0, A0A7P0Z444, A0A7P0Z4B6, A0A7P0Z4N8, B4DWE7, F8VPW7, F8VUC8, H0YIB8, S4R3A5, S4R467

UniProt curated annotations — full annotation on UniProt →

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 higher oligomers 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. Involved in intercellular immune signaling that limits local spread of RNA virus infection and protects against tumorigenesis. Can generate high levels of 2’,5’-oligoadenylates in transformed cells, targeting them to innate and adaptive immunesurveillance mechanisms. Can mediate the antiviral effect via the classical RNase L-dependent pathway or an alternative antiviral pathway independent of RNase L. The secreted form displays antiviral effect against vesicular stomatitis virus (VSV), herpes simplex virus type 2 (HSV-2), and encephalomyocarditis virus (EMCV) and stimulates the alternative antiviral pathway independent of RNase L. When prenylated at C-terminal, acts as a double-stranded RNA (dsRNA) sensor specifically targeted to membranous replicative organelles in SARS coronavirus-2/SARS-CoV-2 infected cells where it binds to dsRNA structures in the SARS-CoV-2 5’-UTR and initiates a potent block to SARS-CoV-2 replication. Recognizes short stretches of dsRNA and activates RNase L. The binding is remarkably specific, with two conserved stem loops in the SARS-CoV-2 5’- untranslated region (UTR) constituting the principal viral target. The same mechanism is necessary to initiate a block to cardiovirus EMCV. Not prenylated at C-terminal, is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.

Subunit / interactions. Monomer. Homotetramer.

Subcellular location. Cytoplasm. Mitochondrion. Nucleus. Microsome. Endoplasmic reticulum. Secreted.

Tissue specificity. Expressed in lungs.

Post-translational modifications. Prenylated at C-terminal. C-terminal prenylation is necessary to initiate a block to SARS-CoV-2 and is associated with protection from severe COVID-1. The prenylated form is targeted to perinuclear structures rich in viral dsRNA, whereas the non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication. C-terminal prenylation is also necessary to initiate a block to cardiovirus EMCV. Not prenylated at C-terminal. The non-prenylated form is diffusely localized and unable to initiate a detectable block to SARS-CoV-2 replication.

Disease relevance. Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia (IMD100) [MIM:618042] An autosomal dominant disorder characterized by onset of respiratory insufficiency due to pulmonary alveolar proteinosis in the first months of life. Disease development appears to be influenced or triggered by viral infection. Patients also have hypogammaglobulinemia, leukocytosis, and splenomegaly. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Produced as a latent enzyme which is activated by dsRNA generated during the course of viral infection. The dsRNA activator must be at least 15 nucleotides long, and no modification of the 2’-hydroxyl group is tolerated. ssRNA or dsDNA do not act as activators.

Induction. By type I interferon (IFN) and viruses.

Polymorphism. Polymorphism dbSNP:rs10774671 is associated with protection against severe COVID-19 disease. In humans, the OAS1 protein is expressed as two major forms designated p46 and p42. The longer p46 isoform is generated by alternative splicing to an exon downstream of the terminal exon used by the p42 isoform. Although all human genotypes contain the exon that completes the transcript encoding p46, an intronic SNP (rs10774671) determines OAS1 exon usage. Alleles with a G at this SNP (G alleles) specify expression of the p46 isoform and some p42, whereas alleles with A at this position predominantly encode the p42 isoform and cannot express the p46 isoform. The p42 isoform, which is the most common isoform in humans (~61% of alleles), has no detectable anti-SARS-CoV-2 activity. The p46 isoform has anti-SARS-CoV-2 activity.

Similarity. Belongs to the 2-5A synthase family.

Isoforms (4)

UniProt ID	Names	Canonical?
P00973-1	p46, 46 kDa, E18	yes
P00973-2	p42, 41 kDa, E16, 3-9, p41
P00973-3	p48, 9-2
P00973-4	p44

RefSeq proteins (15): NP_001027581, NP_001307080, NP_001392949, NP_001392950, NP_001392951, NP_001392952, NP_001392953, NP_001392954, NP_001392955, NP_001392956, NP_001392958, NP_001392959, NP_001399157, NP_002525, NP_058132* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002934	Polymerase_NTP_transf_dom	Domain
IPR006116	NT_2-5OAS_ClassI-CCAase	Domain
IPR006117	2-5OAS_C_CS	Conserved_site
IPR018952	2-5-oligoAdlate_synth_1_dom2/C	Domain
IPR043518	2-5OAS_N_CS	Conserved_site
IPR043519	NT_sf	Homologous_superfamily

Pfam: PF01909, PF10421

Enzyme classification (BRENDA):

• EC 2.7.7.84 — 2’-5’ oligoadenylate synthase (BRENDA: 12 organisms, 43 substrates, 21 inhibitors, 5 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
NAD+	0.0011–0.0014	3
ATP	0.0004–0.0017	2

Catalyzed reactions (Rhea), 1 shown:

• 3 ATP = 5’-triphosphoadenylyl-(2’->5’)-adenylyl-(2’->5’)-adenosine + 2 diphosphate (RHEA:34407)

UniProt features (78 total): helix 15, sequence variant 10, sequence conflict 10, strand 10, mutagenesis site 9, binding site 7, turn 7, splice variant 5, region of interest 2, chain 1, site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
4IG8	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P00973-F1	84.17	0.67

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 158 (interaction with dsrna)

Ligand- & substrate-binding residues (7): 63; 75; 77; 148; 210; 213; 229

Post-translational modifications (1): 397

Mutagenesis-validated functional residues (9):

Position	Phenotype
66	decreased enzyme activity.
75	loss of activity; when associated with a-77.
77	loss of activity; when associated with a-75.
148	strongly reduced enzyme activity.
233	loss of enzyme activity.
331	loss of activity; when associated with a-332 and a-333.
332	loss of activity; when associated with a-331 and a-333.
333	loss of activity; when associated with a-331 and a-332.
397	not prenylated and diffusely distributed. loss of antiviral activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-8983711	OAS antiviral response
R-HSA-909733	Interferon alpha/beta signaling

MSigDB gene sets: 532 (showing top): TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_CELLULAR_RESPONSE_TO_VIRUS, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, BROWNE_HCMV_INFECTION_8HR_UP, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GOBP_NEGATIVE_REGULATION_OF_VIRAL_PROCESS, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION

GO Biological Process (28): glucose metabolic process (GO:0006006), response to virus (GO:0009615), positive regulation of interferon-beta production (GO:0032728), positive regulation of tumor necrosis factor production (GO:0032760), toll-like receptor 3 signaling pathway (GO:0034138), toll-like receptor 4 signaling pathway (GO:0034142), cellular response to interferon-alpha (GO:0035457), cellular response to interferon-beta (GO:0035458), glucose homeostasis (GO:0042593), defense response to bacterium (GO:0042742), surfactant homeostasis (GO:0043129), negative regulation of viral genome replication (GO:0045071), protein complex oligomerization (GO:0051259), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), regulation of ribonuclease activity (GO:0060700), interleukin-27-mediated signaling pathway (GO:0070106), cellular response to exogenous dsRNA (GO:0071360), positive regulation of monocyte chemotactic protein-1 production (GO:0071639), negative regulation of IP-10 production (GO:0071659), cellular response to virus (GO:0098586), antiviral innate immune response (GO:0140374), positive regulation of cellular respiration (GO:1901857), negative regulation of chemokine (C-X-C motif) ligand 2 production (GO:2000342), immune system process (GO:0002376), innate immune response (GO:0045087), defense response to other organism (GO:0098542)

GO Molecular Function (9): 2’-5’-oligoadenylate synthetase activity (GO:0001730), double-stranded RNA binding (GO:0003725), ATP binding (GO:0005524), metal ion binding (GO:0046872), nucleotide binding (GO:0000166), RNA binding (GO:0003723), protein binding (GO:0005515), transferase activity (GO:0016740), nucleotidyltransferase activity (GO:0016779)

GO Cellular Component (9): extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrion (GO:0005739), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), ribosome (GO:0005840), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Interferon Signaling	2
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
intracellular membrane-bounded organelle	3
cytoplasm	3
cellular response to cytokine stimulus	2
defense response	2
hexose metabolic process	1
response to other organism	1
positive regulation of type I interferon production	1
interferon-beta production	1
regulation of interferon-beta production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
positive regulation of tumor necrosis factor superfamily cytokine production	1
endolysosomal toll-like receptor signaling pathway	1
cell surface toll-like receptor signaling pathway	1
response to interferon-alpha	1
response to interferon-beta	1
carbohydrate homeostasis	1
response to bacterium	1
multicellular organismal-level chemical homeostasis	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
protein-containing complex assembly	1
response to virus	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
RNA nuclease activity	1
regulation of catalytic activity	1
regulation of RNA metabolic process	1
cytokine-mediated signaling pathway	1
response to exogenous dsRNA	1
cellular response to dsRNA	1
positive regulation of chemokine production	1
monocyte chemotactic protein-1 production	1
regulation of monocyte chemotactic protein-1 production	1

Protein interactions and networks

STRING

1624 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OAS1	RNASEL	Q05823	924
OAS1	ISG15	P05161	923
OAS1	MX1	P20591	922
OAS1	EIF2AK2	P19525	847
OAS1	IFIT2	P09913	831
OAS1	RSAD2	Q8WXG1	821
OAS1	IFI44	Q8TCB0	820
OAS1	IRF7	Q92985	817
OAS1	STAT1	P42224	816
OAS1	IFI6	P09912	815
OAS1	IFI27	P40305	814
OAS1	IFIT1	P09914	811
OAS1	IFI44L	Q53G44	806
OAS1	USP18	Q9UMW8	805
OAS1	IFITM1	P13164	782

IntAct

23 interactions, top by confidence:

A	B	Type	Score
ACTN1	OAS1	psi-mi:“MI:0915”(physical association)	0.670
TRIM27	OAS1	psi-mi:“MI:0915”(physical association)	0.670
OAS1	ACTN1	psi-mi:“MI:0915”(physical association)	0.670
OAS1	TRIM27	psi-mi:“MI:0915”(physical association)	0.670
EXOC5	OAS1	psi-mi:“MI:0915”(physical association)	0.560
OAS1	EXOC5	psi-mi:“MI:0915”(physical association)	0.560
PRMT6	OAS1	psi-mi:“MI:0915”(physical association)	0.510
OAS1	PRPF8	psi-mi:“MI:0915”(physical association)	0.400
	OAS1	psi-mi:“MI:0915”(physical association)	0.400
RPL30	OAS1	psi-mi:“MI:0915”(physical association)	0.370
BUD23	OAS1	psi-mi:“MI:0915”(physical association)	0.370
GRN	OPA1	psi-mi:“MI:0914”(association)	0.350
OAS1	UBA6	psi-mi:“MI:0914”(association)	0.350
INSR	ATOX1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): OAS1 (Two-hybrid), TRIM27 (Two-hybrid), EXOC5 (Two-hybrid), ACTN1 (Two-hybrid), EXOC5 (Two-hybrid), TRIM27 (Two-hybrid), OAS1 (Co-localization), OAS1 (Proximity Label-MS), OAS1 (Two-hybrid), HOOK2 (Two-hybrid), COG6 (Two-hybrid), BBS4 (Two-hybrid), GOLGA2 (Two-hybrid), RUFY1 (Two-hybrid), TRIM27 (Two-hybrid)

ESM2 similar proteins: A0A2B4RP11, A0A482WD11, A0A6J1SUS3, A0A8B6XWW9, A1ZA55, A4FV14, A4IIW0, A7SFB5, A8DYP7, A8E4S7, B3NQ14, B4QGZ2, D6WI29, G2SLH8, O70299, P00973, P0DV11, P0DV12, P0DXB4, P0DXB5, P0DXB6, P0DXB7, P0DXB8, P0DXC0, P11928, Q05961, Q0IES7, Q0IES8, Q0V9X7, Q13394, Q20054, Q29H55, Q29H56, Q5BKD0, Q5TW90, Q60856, Q6DCQ5, Q6GQD9, Q6NYB4, Q7QHX4

Diamond homologs: E9Q9A9, F1N3B8, G3V645, P00973, P11928, P29728, Q05961, Q15646, Q29599, Q5BKD0, Q5MYT7, Q5MYT9, Q5MYU0, Q60856, Q8VI93, Q8VI94, Q8VI95, Q924S2, Q9Y6K5, Q9Z2F2, G1SK22, P0C224, P0C273, P0C275, P0C276, P0DXC2, P14794, P14795, P14799, P15357, P16709, P18101, P19848, P29504, P46575, P49633, P62975, P62978, P62979, P62982

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

344 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	1
Uncertain significance	165
Likely benign	110
Benign	37

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
1686989	NM_016816.4(OAS1):c.362T>G (p.Val121Gly)	Pathogenic
548129	NM_016816.4(OAS1):c.592C>G (p.Leu198Val)	Likely pathogenic

SpliceAI

1052 predictions. Top by Δscore:

Variant	Effect	Δscore
12:112908656:GAAAT:G	donor_gain	1.0000
12:112908534:AG:A	acceptor_gain	0.9900
12:112908534:AGGGT:A	acceptor_gain	0.9900
12:112908535:GG:G	acceptor_gain	0.9900
12:112908535:GGGT:G	acceptor_gain	0.9900
12:112908535:GGGTG:G	acceptor_gain	0.9900
12:112908657:A:T	donor_gain	0.9900
12:112908674:G:GT	donor_gain	0.9900
12:112908706:G:GT	donor_gain	0.9900
12:112911236:G:GG	donor_gain	0.9900
12:112916507:A:AG	acceptor_gain	0.9900
12:112916507:AGT:A	acceptor_gain	0.9900
12:112916508:G:GG	acceptor_gain	0.9900
12:112916508:GT:G	acceptor_gain	0.9900
12:112916508:GTG:G	acceptor_gain	0.9900
12:112916676:G:GG	donor_gain	0.9900
12:112916679:T:TG	donor_gain	0.9900
12:112908531:TTCA:T	acceptor_loss	0.9800
12:112908532:TCA:T	acceptor_loss	0.9800
12:112908533:CAG:C	acceptor_loss	0.9800
12:112908534:A:AC	acceptor_loss	0.9800
12:112908623:GA:G	donor_gain	0.9800
12:112908717:TCC:T	donor_gain	0.9800
12:112908754:C:G	donor_gain	0.9800
12:112908760:ACTG:A	donor_gain	0.9800
12:112916508:GTGTA:G	acceptor_gain	0.9800
12:112916675:A:AG	donor_gain	0.9800
12:112918771:C:G	donor_gain	0.9800
12:112908629:T:G	donor_gain	0.9700
12:112908705:TG:T	donor_gain	0.9700

AlphaMissense

2627 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:112911170:T:C	F197L	0.996
12:112911172:C:A	F197L	0.996
12:112911172:C:G	F197L	0.996
12:112911137:T:C	F186L	0.995
12:112911139:C:A	F186L	0.995
12:112911139:C:G	F186L	0.995
12:112917608:T:A	W316R	0.994
12:112917608:T:C	W316R	0.994
12:112911099:T:C	L173P	0.992
12:112911171:T:C	F197S	0.992
12:112911224:T:A	W215R	0.992
12:112911224:T:C	W215R	0.992
12:112916555:T:C	L234P	0.991
12:112917610:G:C	W316C	0.991
12:112917610:G:T	W316C	0.991
12:112908596:T:C	F81L	0.990
12:112908598:C:A	F81L	0.990
12:112908598:C:G	F81L	0.990
12:112908617:T:C	F88L	0.990
12:112908619:T:A	F88L	0.990
12:112908619:T:G	F88L	0.990
12:112916668:T:A	W272R	0.990
12:112916668:T:C	W272R	0.990
12:112917561:A:G	D300G	0.990
12:112917564:C:A	P301Q	0.990
12:112908812:T:C	F153L	0.989
12:112908814:T:A	F153L	0.989
12:112908814:T:G	F153L	0.989
12:112911149:T:C	F190L	0.989
12:112911151:C:A	F190L	0.989

dbSNP variants (sampled 300 via entrez): RS1000101788 (12:112929102 C>A,G), RS1000290508 (12:112911094 C>G,T), RS1000349725 (12:112929292 G>A), RS1000418876 (12:112917988 C>G,T), RS1000476965 (12:112905205 A>G), RS1000641106 (12:112910846 C>T), RS1000858817 (12:112924349 T>TGGCCCTTTTTATCGA), RS1000877523 (12:112928462 T>C), RS1000884175 (12:112924976 T>C), RS1000956788 (12:112930569 G>A,T), RS1000978235 (12:112922388 G>A), RS1000981740 (12:112924668 C>T), RS1001149812 (12:112928176 A>G), RS1001221057 (12:112928782 T>G), RS1001273391 (12:112929070 T>A)

Disease associations

OMIM: gene MIM:164350 | disease phenotypes: MIM:618042

GenCC curated gene-disease

Disease	Classification	Inheritance
pulmonary alveolar proteinosis with hypogammaglobulinemia	Strong	Autosomal dominant

Mondo (1): pulmonary alveolar proteinosis with hypogammaglobulinemia (MONDO:0020840)

Orphanet (1): Infantile-onset pulmonary alveolar proteinosis-hypogammaglobulinemia (Orphanet:572428)

HPO phenotypes

11 total (11 of 11 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0001522	Death in infancy
HP:0001744	Splenomegaly
HP:0001974	Increased total leukocyte count
HP:0002093	Respiratory insufficiency
HP:0002205	Recurrent respiratory infections
HP:0003593	Infantile onset
HP:0003819	Death in childhood
HP:0004313	Decreased circulating immunoglobulin concentration
HP:0006517	Intraalveolar phospholipid accumulation
HP:0011421	Death in adolescence

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001738_6	Response to fenofibrate (adiponectin levels)	5.000000e-08
GCST001965_4	Glycemic traits	5.000000e-09
GCST005951_2	Body mass index	9.000000e-09
GCST006585_2766	Blood protein levels	6.000000e-08
GCST007840_2	Low HDL-cholesterol levels	2.000000e-07
GCST007840_3	Low HDL-cholesterol levels	6.000000e-12
GCST007921_2	Right-sided colonic diverticulosis	7.000000e-06
GCST008972_117	Urate levels	5.000000e-19

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2660	OAS1		0.00	0

CTD chemical–gene interactions

106 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, decreases reaction	6
Poly I-C	decreases reaction, increases expression, affects cotreatment, increases activity, increases abundance	4
Tretinoin	affects expression, increases expression	4
Cyclosporine	decreases expression, increases expression	4
2’,5’-oligoadenylate	affects binding, increases activity, increases expression, increases chemical synthesis, increases metabolic processing (+2 more)	3
Estradiol	affects cotreatment, increases expression, decreases expression	3
Lipopolysaccharides	affects expression, increases expression, affects reaction, affects response to substance	3
Nickel	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	increases expression, decreases expression, affects cotreatment	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
bisphenol A	decreases expression, decreases methylation	2
Air Pollutants	increases expression, decreases expression, increases abundance	2
Nicotine	decreases reaction, increases expression	2
Plant Extracts	affects expression, affects reaction, increases expression	2
Silicon Dioxide	increases expression	2
Testosterone	affects cotreatment, increases expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
aristolochic acid I	increases expression	1
6-hydroxy-3-O-methylkaempferol 6-O-glucopyranoside	increases expression, increases reaction	1
sotorasib	affects cotreatment, increases expression	1
tetrabromobisphenol S	decreases expression	1
propionaldehyde	increases expression	1
chlorophyllin	decreases reaction, increases expression	1
sodium arsenate	decreases expression, increases abundance	1
arsenite	affects binding, increases reaction	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	increases expression	1
tetrabromobisphenol A	decreases expression	1
perfluorooctanoic acid	decreases expression	1

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1ZF	Abcam HeLa OAS1 KO	Cancer cell line	Female
CVCL_B2P8	Abcam A-549 OAS1 KO 2	Cancer cell line	Male
CVCL_B9CR	Abcam A-549 OAS1 KO 1	Cancer cell line	Male
CVCL_E0JG	Ubigene HeLa OAS1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.