OAS2

protein-coding

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

Gene summary

This gene encodes a member of the 2-5A synthetase family, essential proteins involved in the innate immune response to viral infection. The encoded protein is induced by interferons and uses adenosine triphosphate in 2'-specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates (2-5As). These molecules activate latent RNase L, which results in viral RNA degradation and the inhibition of viral replication. The three known members of this gene family are located in a cluster on chromosome 12. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

MANE transcript

NM_002535.3

Inheritance

ClinVar variants

P:1U:91B:16

Top phenotype

multisystem inflammatory syndrome in children and adults

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr12:112,978,395-113,011,723

External References & Databases

Ensembl (ENSG00000111335)

Transcript & Mutation Effects

hg38 • Region Span ~33.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

multisystem inflammatory syndrome in children and adultsSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0035375

Submitter: PanelApp Australia

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to OAS2 variants in ClinVar

3 Conditions Cataloged

not specifiedTotal: 95

not providedTotal: 5

Autoinflammation and autoimmunity with immune dysregulation 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002535.3. 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			3 clinvar	1 clinvar	4 clinvar	8
missense	1 clinvar		86 clinvar	11 clinvar		98
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	91	12	4	108

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002535.3	RefSeq	NP_002526.2	10	MANE Select
ENST00000392583.7	Ensembl	ENSP00000376362.3	10	MANE Select
NM_001032731.2	RefSeq	NP_001027903.1	2	Standard
NM_016817.3	RefSeq	NP_058197.2	11	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

nucleobase-containing compound metabolic process
RNA catabolic process
response to virus
response to bacterium
defense response to virus

Molecular Function

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

Cellular Component

nucleus
nucleoplasm
cytosol
membrane
intracellular membrane-bounded organelle

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000342315
Coding exons: 11
Length: 33329
Individuals with no LoFs: 125588
Homozygous LoFs: 0
Heterozygous LoFs: 159
Defined: 125747
p: 0.000632

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.378	371	392	0.946	0.0000215	4728
Missense (PolyPhen)		118	129.28	0.91275		1719
Synonymous	-0.0868	161	160	1.01	0.00000930	1347
Loss of Function	0.365	33	35.3	0.934	0.00000174	399

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0031	0.0031	notable
Latino/Admixed American	0.00090	0.00090	rare
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00049	0.00049	rare
Finnish	0.00028	0.00028	rare
European (Non-Finnish)	0.00035	0.00033	rare
South Asian	0.00062	0.00062	rare
Other	0.00065	0.00065	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response (PubMed:10464285, PubMed:9880569). Activated by detection of double stranded RNA (dsRNA): polymerizes higher oligomers of 2'- 5'-oligoadenylates (2-5A) from ATP which then bind to the inactive monomeric form of ribonuclease L (RNASEL) leading to its dimerization and subsequent activation (PubMed:10464285, PubMed:9880569, PubMed:11682059). Activation of RNASEL leads to degradation of cellular as well as viral RNA, resulting in the inhibition of protein synthesis, thus terminating viral replication (PubMed:10464285, PubMed:9880569). Can mediate the antiviral effect via the classical RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL (PubMed:21142819). In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation (PubMed:21142819). May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates (By similarity). Non-infected lobules would not be affected, allowing efficient pup feeding during infection (By similarity). {ECO:0000250|UniProtKB:E9Q9A9, ECO:0000269|PubMed:10464285, ECO:0000269|PubMed:11682059, ECO:0000269|PubMed:19923450, ECO:0000269|PubMed:9880569, ECO:0000303|PubMed:21142819}.;

Recessive Scores

pRec: 0.104

Intolerance Scores

LoFtool: 0.983
RVIS EVS: -1.08
RVIS percentile EVS: 7.2

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.186

Gene Damage Prediction

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