OAS1

protein-coding

2'-5'-oligoadenylate synthetase 1, the group of 2'-5'-oligoadenylate synthetase family

Gene summary

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. [provided by RefSeq, May 2022]

Previous symbols:

OIAS

MANE transcript

NM_016816.4

Inheritance

AD, AR

ClinVar variants

P:2U:178B:147

Top phenotype

Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia

gnomAD constraint

pLI —, LoF o/e 0.55

Max pathogenic AF

—

Genomic locus

chr12:112,905,856-112,933,219

External References & Databases

Ensembl (ENSG00000089127)

Transcript & Mutation Effects

hg38 • Region Span ~27.4 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

pulmonary alveolar proteinosis with hypogammaglobulinemiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020840

Submitter: Labcorp Genetics (formerly Invitae)

pulmonary alveolar proteinosis with hypogammaglobulinemiaSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0020840

Submitter: PanelApp Australia

pulmonary alveolar proteinosis with hypogammaglobulinemiaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0020840

Submitter: PanelApp Australia

Clinical Genomic Database (CGD)

Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemiaAD

Manifestation: Allergy/Immunology/Infectious; Pulmonary

Intervention: Allergy/Immunology/Infectious; Pulmonary

Rationale: Recurrent infections have been described, and preventive measures and awareness allowing early diagnosis and aggressive treatmentment of infections may be beneficial; Individuals may suffer from severe and early-onset respiratory insufficiency, and early awareness may be beneficial for pulmonary management, including related to ventilatory support; HSCT has been described

Refs: 29185156; 29455859; 34145065

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OAS1 variants in ClinVar

4 Conditions Cataloged

not providedTotal: 338

not specifiedTotal: 71

Pulmonary alveolar proteinosis with hypogammaglobulinemiaTotal: 13

OAS1-related disorderTotal: 11

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_016816.4. 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			1 clinvar	69 clinvar	6 clinvar	76
missense	1 clinvar	1 clinvar	153 clinvar	55 clinvar	13 clinvar	223
nonsense			6 clinvar	2 clinvar		8
start loss			2 clinvar			2
frameshift			8 clinvar	2 clinvar		10
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	1	1	178	128	19	327

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 78 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_016816.4	RefSeq	NP_058132.2	6	MANE Select
ENST00000202917.10	Ensembl	ENSP00000202917.5	6	MANE Select
NM_001032409.3	RefSeq	NP_001027581.1	6	Standard
NM_001320151.2	RefSeq	NP_001307080.1	6	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

glucose metabolic process
response to virus
glucose homeostasis
negative regulation of viral genome replication
defense response to virus

Molecular Function

2'-5'-oligoadenylate synthetase activity
double-stranded RNA binding
protein binding
ATP binding
metal ion binding

Cellular Component

extracellular region
nucleus
nucleoplasm
cytoplasm
mitochondrion

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000445409
Coding exons: 6
Length: 25409
Individuals with no LoFs: 125659
Homozygous LoFs: 0
Heterozygous LoFs: 89
Defined: 125748
p: 0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.426	247	229	1.08	0.0000124	2697
Missense (PolyPhen)		89	83.797	1.0621		1020
Synonymous	1.14	80	94.0	0.851	0.00000524	809
Loss of Function	1.80	10	18.3	0.546	0.00000100	197

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00086	0.00086	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.0021	0.0021	notable
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00012	0.00012	rare
South Asian	0.000098	0.000098	rare
Other	0.00082	0.00081	rare

dbNSFP Gene Annotations

Source: dbNSFP

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 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. 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. {ECO:0000269|PubMed:12799444, ECO:0000269|PubMed:18931074, ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:23319625}.;

Recessive Scores

pRec: 0.190

Intolerance Scores

LoFtool: 0.979
RVIS EVS: 1.31
RVIS percentile EVS: 94.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.613

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium