Alt. symbols: OIAS | OIASI | IFI-4

Approved name: 2'-5'-oligoadenylate synthetase 1
Alt. names: 2',5'-oligoadenylate synthetase 1 (40-46 kD), 2'-5'-oligoadenylate synthetase 1, 40/46kDa | 2'-5' oligoadenylate synthase 1

Location: 12q24.13: 112905856 - 112933219 (+)
Gene type: protein_coding, 33 transcripts.

Scores: LoFtool: 0.979000 | pLI: 0.00123924 | LOEUF: 0.927

HGNC: 8086

NCBI: 4938, RefSeq: NG_011530.2

Ensembl: ENSG00000089127.15

LRG_ | Status: none

OMIM: 164350

Expression | ProteinAtlas

OAS1 encodes an interferon-induced, dsRNA-activated antiviral enzyme, which belongs to the 2-5A synthetase family and that plays a critical role in cellular innate antiviral response. This enyzme 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. OAS1 can mediate the antiviral effect either via the classical RNase L-dependent pathway or via 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. In addition, OAS1 may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation.

OAS1 polymorphisms have been implicated as both protective and risk alleles for severe responses to viral infections including COVID-19 (PMID: 33633408, 33791713, 34282422, 34581622). Cho et al. (2018) identified 3 different rare de novo heterozygous missense OAS1 variants in 5 Japanese patients, including 3 siblings, with infantile-onset pulmonary alveolar proteinosis (PAP) and hypogammaglobulinemia (PMID: 29455859), in some cases after documented viral infection. 3 of 5 individuals surviving b eyond age 1 year old showed low IgG, IgA, and IgM despite the lack of an overt B cell deficiency, 3 showed significant inflammation, and 4 showed splenomegaly. BAL in one patient showed small and non-foamy alveolar macrophages (AMs), suggesting dysfunction of maturation and/or phagocytosis of AMs rather than impaired catabolism of phagocytosed lung surfactant. The authors hypothesized that these variants exerted a GOF effect, leading to an exaggerated immune reaction in response to viral infections, AM dysfunction and impaired catabolism of lung surfactant. Magg et al. (2021) identified the same 3 variants and one additional de novo heterozygous missense variant in 6 patients (1 previously reported) with early-onset recurrent fevers, dermatitis, IBD, PAP, and hypogammaglobulinemia (PMID: 34145065). Patients had normal T-cell counts, but low monocytes and B-cells during flares. The authors showed that the OAS1 variants resulted in gain of dsRNA-independent activity upon IFN induction, resulting in RNase L-mediated RNA cleavage, transcriptomic alteration, translational arrest and monocyte/macrophage and B cell dysfunction and apoptosis. RNase L inhibition by curcumin modulated the clinical phenotype, which was corrected in 2 of 4 patients receiving alloHSCT. Lee et al. (2023) identified biallelic OAS1 LOF mutations in children with MIS-C, acting via production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes (PMID: 36538032). [Load More]