OAS2

Summary

OAS2 (2’-5’-oligoadenylate synthetase 2, HGNC:8087) is a protein-coding gene on chromosome 12q24.13, encoding 2’-5’-oligoadenylate synthase 2 (P29728). Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response.

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.

Source: NCBI Gene 4939 — RefSeq curated summary.

At a glance

• Gene–disease (curated): multisystem inflammatory syndrome in children and adults (Strong, GenCC)
• GWAS associations: 9
• Clinical variants (ClinVar): 110 total — 1 pathogenic
• Phenotypes (HPO): 31
• MANE Select transcript: NM_002535

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8087
Approved symbol	OAS2
Name	2’-5’-oligoadenylate synthetase 2
Location	12q24.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000111335
Ensembl biotype	protein_coding
OMIM	603350
Entrez	4939

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 7 protein_coding, 4 nonsense_mediated_decay, 4 retained_intron

ENST00000342315, ENST00000392583, ENST00000449768, ENST00000551603, ENST00000552756, ENST00000620097, ENST00000679877, ENST00000680122, ENST00000680138, ENST00000680514, ENST00000680666, ENST00000680685, ENST00000680898, ENST00000681023, ENST00000681673

RefSeq mRNA: 3 — MANE Select: NM_002535 NM_001032731, NM_002535, NM_016817

CCDS: CCDS31906, CCDS41839, CCDS44982

Canonical transcript exons

ENST00000392583 — 10 exons

Exon	Start	End
ENSE00000755397	113006413	113006600
ENSE00000834927	112987038	112987308
ENSE00000834932	113004934	113005222
ENSE00000834934	113007705	113007943
ENSE00001512433	113009087	113011723
ENSE00002421397	112978519	112978785
ENSE00003588533	112995296	112995474
ENSE00003622776	112998266	112998410
ENSE00003650693	113002932	113003102
ENSE00003670409	112997520	112997755

Expression profiles

Bgee: expression breadth ubiquitous, 226 present calls, max score 95.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.6584 / max 2238.3856, expressed in 1072 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
128126	12.7726	858
128124	5.5646	742
128123	3.5037	575
128125	2.6077	560
128122	0.8709	294
128121	0.3276	166
128128	0.0113	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	95.99	gold quality
leukocyte	CL:0000738	95.92	gold quality
mononuclear cell	CL:0000842	95.87	gold quality
granulocyte	CL:0000094	94.13	gold quality
lymph node	UBERON:0000029	89.22	gold quality
decidua	UBERON:0002450	88.75	gold quality
vermiform appendix	UBERON:0001154	88.66	gold quality
gall bladder	UBERON:0002110	88.14	gold quality
spleen	UBERON:0002106	87.86	gold quality
right lung	UBERON:0002167	85.99	gold quality
blood	UBERON:0000178	85.72	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.21	gold quality
bone marrow cell	CL:0002092	84.08	gold quality
upper lobe of left lung	UBERON:0008952	83.87	gold quality
apex of heart	UBERON:0002098	83.74	gold quality
upper lobe of lung	UBERON:0008948	83.40	gold quality
tonsil	UBERON:0002372	82.36	gold quality
rectum	UBERON:0001052	82.13	gold quality
caecum	UBERON:0001153	81.67	gold quality
esophagus mucosa	UBERON:0002469	81.66	gold quality
smooth muscle tissue	UBERON:0001135	80.91	gold quality
palpebral conjunctiva	UBERON:0001812	80.60	gold quality
right coronary artery	UBERON:0001625	80.32	gold quality
lung	UBERON:0002048	80.27	gold quality
lower esophagus mucosa	UBERON:0035834	79.05	gold quality
calcaneal tendon	UBERON:0003701	79.01	gold quality
omental fat pad	UBERON:0010414	78.82	gold quality
descending thoracic aorta	UBERON:0002345	78.75	gold quality
peritoneum	UBERON:0002358	78.71	gold quality
lower lobe of lung	UBERON:0008949	78.47	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7037	yes	394.18
E-ANND-3	yes	5.67
E-GEOD-98556	no	20.90

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ETS1, STAT1, STAT2

miRNA regulators (miRDB)

72 targeting OAS2, 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-6870-5P	99.99	68.55	2115
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-544A	99.84	68.66	1965
HSA-MIR-6844	99.82	70.69	2423
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-2116-3P	99.74	64.32	889
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-3177-5P	99.65	70.38	1174
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6716-5P	99.56	68.62	1244
HSA-MIR-4753-5P	99.54	68.51	1356
HSA-MIR-136-5P	99.50	67.26	1153

Literature-anchored findings (GeneRIF, showing 16)

• 2’-5’-oligoadenylate synthetase type 2 (OAS2), a dsRNA binding protein involved in the pathway that activates RNase-L, is identified as a new binding partner for NOD2. (PMID:19853919)
• The data suggest a possible association between OAS2 and OAS3 single nucleotide polymorphisms and the outcome of tick-borne encephalitis virus infection in a Russian population. (PMID:21050126)
• The results suggest that OAS1-OAS3-OAS2 haplotypes are associated with differential susceptibility to clinical outcomes of dengue infection. (PMID:23337612)
• Primary mononuclear cells from patients with systemic sclerosis have increased basal levels of OASL and OAS2 genes. (PMID:24328427)
• Data obtained suggest that the OAS2 rs1293762 and CD209 rs2287886 SNPs are associated with predisposition to chronic hepatitis C in Russian population. (PMID:24594345)
• Suggest 2'5’-oligoadenylate synthetase 2 mediates T-cell receptor CD3-zeta chain down-regulation via caspase-3 activation in oral cancer. (PMID:26595239)
• Epigenetic regulation of OAS2 shows disease-specific DNA methylation profiles at individual CpG sites. (PMID:27572959)
• we characterized the functional consequences of the Neandertal haplotype in the transcriptional regulation of OAS genes at baseline and infected conditions. We found that cells from people with the Neandertal-like haplotype express lower levels of OAS3 upon infection, as well as distinct isoforms of OAS1 and OAS2 (PMID:27899133)
• Mx1 and OAS1-2 polymorphisms were associated with the severity of liver disease in HIV/HCV-coinfected patients, suggesting a significant role in the progression of hepatic fibrosis. (PMID:28139728)
• OAS2 rs739901 5’-flanking C/A genetic polymorphisms involve the susceptibility to EV71 infection, and A allele might be a risk factor of the susceptibility to EV-71 infection. (PMID:30128873)
• Low OAS2 expression is associated with colorectal cancer metastasis, mediating perineural and lymphovascular invasion. (PMID:30148861)
• The OAS2 showed a marked increase in activity with increasing dsRNA length with a minimum requirement of 35 bp. (PMID:30965010)
• Structural and Hydrodynamic Characterization of Dimeric Human Oligoadenylate Synthetase 2. (PMID:32413313)
• Quantitative Proteomic Profile of Psoriatic Epidermis Identifies OAS2 as a Novel Biomarker for Disease Activity. (PMID:32849499)
• Long noncoding RNA SATB1-AS1 contributes to the chemotherapy resistance through the microRNA-580/ 2’-5’-oligoadenylate synthetase 2 axis in acute myeloid leukemia. (PMID:34516354)
• OAS1, OAS2, and OAS3 Contribute to Epidermal Keratinocyte Proliferation by Regulating Cell Cycle and Augmenting IFN-1Induced Jak1Signal Transducer and Activator of Transcription 1 Phosphorylation in Psoriasis. (PMID:35305973)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Oas2	ENSMUSG00000032690
rattus_norvegicus	Oas2	ENSRNOG00000049282

Paralogs (3): OAS1 (ENSG00000089127), OAS3 (ENSG00000111331), OASL (ENSG00000135114)

Protein

Protein identifiers

2’-5’-oligoadenylate synthase 2 — P29728 (reviewed: P29728)

Alternative names: p69 OAS / p71 OAS

All UniProt accessions (8): P29728, A0A087X0V5, A0A7P0T8H9, A0A7P0T9B5, A0A7P0TAE6, A0A7P0TAV1, F8VPI5, F8W1C5

UniProt curated annotations — full annotation on UniProt →

Function. Interferon-induced, dsRNA-activated antiviral enzyme which plays a critical role in cellular innate antiviral response. 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. Activation of RNASEL 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 RNASEL-dependent pathway or an alternative antiviral pathway independent of RNASEL. In addition, it may also play a role in other cellular processes such as apoptosis, cell growth, differentiation and gene regulation. May act as a negative regulator of lactation, stopping lactation in virally infected mammary gland lobules, thereby preventing transmission of viruses to neonates. Non-infected lobules would not be affected, allowing efficient pup feeding during infection.

Subunit / interactions. Homodimer.

Subcellular location. Cytoplasm. Perinuclear region.

Post-translational modifications. Myristoylation is not essential for its activity. Glycosylated. Glycosylation is essential for its activity.

Activity regulation. Produced as a latent enzyme which is activated by double stranded RNA (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. Strongly inhibited by copper, iron and zinc ions. Partially inhibited by cobalt and nickel ions.

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

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

Isoforms (3)

UniProt ID	Names	Canonical?
P29728-1	p71, 71 kDa	yes
P29728-2	p69, 69 kDa
P29728-3	3

RefSeq proteins (3): NP_001027903, NP_002526, NP_058197 (=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 (33 total): mutagenesis site 10, sequence conflict 7, binding site 6, splice variant 4, region of interest 2, initiator methionine 1, chain 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9H1Z	ELECTRON MICROSCOPY	3.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P29728-F1	88.57	0.71

Functional residue map

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

Ligand- & substrate-binding residues (6): 396; 408; 410; 481; 544; 547

Post-translational modifications (2): 378, 2

Mutagenesis-validated functional residues (10):

Position	Phenotype
2	no loss of activity.
408	loss of activity; when associated with a-410.
410	loss of activity; when associated with a-408.
421	significant loss of activity.
481	loss of activity.
544	significant loss of activity.
547	partial loss of activity.
668	loss of activity; when associated with a-669 and a-670.
669	loss of activity; when associated with a-668 and a-670.
670	loss of activity; when associated with a-668 and a-669.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-877300	Interferon gamma signaling
R-HSA-8983711	OAS antiviral response
R-HSA-909733	Interferon alpha/beta signaling
R-HSA-9833110	RSV-host interactions

MSigDB gene sets: 443 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, BROWNE_HCMV_INFECTION_8HR_UP, GOZGIT_ESR1_TARGETS_DN, 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, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, MODULE_16

GO Biological Process (16): nucleobase-containing compound metabolic process (GO:0006139), RNA catabolic process (GO:0006401), response to virus (GO:0009615), positive regulation of interferon-beta production (GO:0032728), positive regulation of tumor necrosis factor production (GO:0032760), defense response to bacterium (GO:0042742), negative regulation of viral genome replication (GO:0045071), defense response to virus (GO:0051607), type I interferon-mediated signaling pathway (GO:0060337), interleukin-27-mediated signaling pathway (GO:0070106), antiviral innate immune response (GO:0140374), regulation of lactation (GO:1903487), immune system process (GO:0002376), response to bacterium (GO:0009617), 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 (6): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), intracellular membrane-bounded organelle (GO:0043231), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Interferon Signaling	2
Antimicrobial mechanism of IFN-stimulated genes	1
Respiratory Syncytial Virus Infection Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
response to other organism	3
defense response	3
intracellular anatomical structure	2
cytoplasm	2
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	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
response to bacterium	1
viral genome replication	1
regulation of viral genome replication	1
negative regulation of viral process	1
response to virus	1
cellular response to type I interferon	1
interferon-mediated signaling pathway	1
cytokine-mediated signaling pathway	1
innate immune response	1
defense response to virus	1
lactation	1
regulation of body fluid levels	1
regulation of secretion	1
regulation of multicellular organismal development	1
biological_process	1
immune response	1
defense response to symbiont	1
adenylyltransferase activity	1
RNA binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
nucleic acid binding	1
binding	1

Protein interactions and networks

STRING

1546 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
OAS2	MX1	P20591	878
OAS2	NOD2	Q9HC29	871
OAS2	RNASEL	Q05823	859
OAS2	IFIT1	P09914	838
OAS2	EIF2AK2	P19525	802
OAS2	IRF7	Q92985	802
OAS2	ICA1	P78506	787
OAS2	IFI6	P09912	782
OAS2	ISG15	P05161	773
OAS2	STAT1	P42224	773
OAS2	RIGI	O95786	744
OAS2	IFIT3	O14879	742
OAS2	IFIT2	P09913	742
OAS2	MX2	P20592	730
OAS2	IFI27	P40305	723

IntAct

10 interactions, top by confidence:

A	B	Type	Score
CLK3	OAS2	psi-mi:“MI:0915”(physical association)	0.670
OAS2	CLK3	psi-mi:“MI:0915”(physical association)	0.670
ATG16L1		psi-mi:“MI:0914”(association)	0.350
CKAP2	WDR46	psi-mi:“MI:0914”(association)	0.350
GIMAP8	SRP72	psi-mi:“MI:0914”(association)	0.350
ATMIN	OAS2	psi-mi:“MI:0914”(association)	0.350
OAS2	ACACA	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): OAS2 (Two-hybrid), OAS2 (Affinity Capture-MS), PRKG1 (Affinity Capture-MS), ACACA (Affinity Capture-MS), OAS2 (Affinity Capture-MS), MB21D1 (Affinity Capture-Western), OAS2 (Two-hybrid), OAS2 (Affinity Capture-MS), CLK3 (Two-hybrid), FBXO17 (Two-hybrid), OAS2 (Affinity Capture-MS), OAS2 (Affinity Capture-MS), OAS2 (Affinity Capture-MS), OAS2 (Affinity Capture-MS), PRKG1 (Affinity Capture-MS)

ESM2 similar proteins: A0A2B4RP11, A0A3M6TIF0, A0A482WD11, A0A6J1SUS3, A0A8B6XWW9, A1ZA55, A4FV14, A4IIW0, A7SFB5, A8DYP7, A8E4S7, B3NQ14, B4QGZ2, D6WI29, O70299, P00973, P0DV11, P0DV12, P0DXB4, P0DXB5, P0DXB6, P0DXB7, P0DXB8, P0DXC0, P11928, P29728, Q05961, Q0IES7, Q0IES8, Q0V9X7, Q13394, Q20054, Q29H55, Q29H56, Q5BKD0, Q5TW90, Q60856, Q6DCQ5, Q6GQD9, Q6NYB4

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	73
Likely benign	12
Benign	2

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4528895	NM_002535.3(OAS2):c.1572C>G (p.Phe524Leu)	Pathogenic

SpliceAI

1749 predictions. Top by Δscore:

Variant	Effect	Δscore
12:112978747:G:GT	donor_gain	1.0000
12:112978774:G:GT	donor_gain	1.0000
12:112978786:G:GG	donor_gain	1.0000
12:112987307:GA:G	donor_gain	1.0000
12:112987309:G:GG	donor_gain	1.0000
12:112995289:A:AG	acceptor_gain	1.0000
12:112995290:C:G	acceptor_gain	1.0000
12:112995291:A:AG	acceptor_gain	1.0000
12:112995291:ATCAG:A	acceptor_gain	1.0000
12:112995292:T:G	acceptor_gain	1.0000
12:112995294:A:AG	acceptor_gain	1.0000
12:112995295:G:GC	acceptor_gain	1.0000
12:112995295:GGC:G	acceptor_gain	1.0000
12:112995295:GGCTT:G	acceptor_gain	1.0000
12:112995470:AACAG:A	donor_loss	1.0000
12:112995473:AGGT:A	donor_loss	1.0000
12:112995474:GGTA:G	donor_loss	1.0000
12:112995475:G:GA	donor_loss	1.0000
12:112995476:T:A	donor_loss	1.0000
12:112997723:G:GT	donor_gain	1.0000
12:113002930:A:AG	acceptor_gain	1.0000
12:113002930:AGCCT:A	acceptor_gain	1.0000
12:113002931:G:GG	acceptor_gain	1.0000
12:113002931:GC:G	acceptor_gain	1.0000
12:113002931:GCC:G	acceptor_gain	1.0000
12:113002931:GCCT:G	acceptor_gain	1.0000
12:113002931:GCCTG:G	acceptor_gain	1.0000
12:113003099:CCGGG:C	donor_loss	1.0000
12:113003101:GG:G	donor_gain	1.0000
12:113003102:GG:G	donor_gain	1.0000

AlphaMissense

4526 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:113006502:T:C	F520L	0.978
12:113006504:T:A	F520L	0.978
12:113006504:T:G	F520L	0.978
12:113006514:T:C	F524L	0.978
12:113006516:C:A	F524L	0.978
12:113006516:C:G	F524L	0.978
12:113004994:T:C	F414L	0.975
12:113004996:C:A	F414L	0.975
12:113004996:C:G	F414L	0.975
12:113007873:T:A	W609R	0.975
12:113007873:T:C	W609R	0.975
12:113003049:T:C	F376L	0.974
12:113003051:C:A	F376L	0.974
12:113003051:C:G	F376L	0.974
12:113009148:T:A	W653R	0.974
12:113009148:T:C	W653R	0.974
12:113005154:T:C	F467S	0.973
12:113005210:T:C	F486L	0.973
12:113005212:T:A	F486L	0.973
12:113005212:T:G	F486L	0.973
12:113005153:T:C	F467L	0.971
12:113005155:C:A	F467L	0.971
12:113005155:C:G	F467L	0.971
12:113006535:T:C	F531L	0.967
12:113006537:C:A	F531L	0.967
12:113006537:C:G	F531L	0.967
12:112997616:T:C	F242L	0.964
12:112997618:T:A	F242L	0.964
12:112997618:T:G	F242L	0.964
12:112995376:T:C	F177L	0.961

dbSNP variants (sampled 300 via entrez): RS1000005248 (12:113010488 T>A,C,G), RS1000109097 (12:112979123 C>G,T), RS1000232251 (12:113004283 C>T), RS1000246033 (12:112986597 C>T), RS1000525694 (12:113000095 A>C), RS1000537760 (12:112991747 A>T), RS1000574013 (12:112986782 A>G), RS1000634340 (12:112978843 A>C,G), RS1000640336 (12:112999748 A>T), RS1000672167 (12:113010855 C>G,T), RS1000713194 (12:112985240 T>A), RS1000758190 (12:112998851 T>G), RS1000936060 (12:112977970 C>A), RS1000988290 (12:112977691 A>G,T), RS1001107822 (12:113006431 C>T)

Disease associations

OMIM: gene MIM:603350 | disease phenotypes: MIM:621409

GenCC curated gene-disease

Disease	Classification	Inheritance
multisystem inflammatory syndrome in children and adults	Strong	Autosomal recessive

Mondo (2): autoinflammation and autoimmunity with immune dysregulation 2 (MONDO:0700392), multisystem inflammatory syndrome in children and adults (MONDO:0035375)

Orphanet (0):

HPO phenotypes

31 total (30 of 31 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000092	Renal tubular atrophy
HP:0000096	Glomerular sclerosis
HP:0000099	Glomerulonephritis
HP:0000421	Epistaxis
HP:0000822	Hypertension
HP:0001250	Seizure
HP:0001269	Hemiparesis
HP:0001342	Cerebral hemorrhage
HP:0001658	Myocardial infarction
HP:0001942	Metabolic acidosis
HP:0002153	Hyperkalemia
HP:0002573	Hematochezia
HP:0002633	Vasculitis
HP:0002907	Microscopic hematuria
HP:0003493	Antinuclear antibody positivity
HP:0004719	Hyperechogenic kidneys
HP:0011116	Abnormal circulating interferon concentration
HP:0011463	Childhood onset
HP:0011675	Arrhythmia
HP:0012251	ST segment elevation
HP:0012593	Nephrotic range proteinuria
HP:0012622	Chronic kidney disease
HP:0020062	Decreased hemoglobin concentration
HP:0030151	Cholangitis
HP:0030948	Elevated gamma-glutamyltransferase level
HP:0032436	Abnormal circulating C-reactive protein concentration
HP:0032948	Renal interstitial fibrosis
HP:0033041	Cytokine storm
HP:0033559	Anti-myeloperoxidase antibody positivity

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST001523_11	Visceral adipose tissue adjusted for BMI	1.000000e-06
GCST001738_6	Response to fenofibrate (adiponectin levels)	5.000000e-08
GCST003833_19	Adult asthma	9.000000e-07
GCST003833_7	Adult asthma	2.000000e-06
GCST005329_1	Coffee consumption	2.000000e-16
GCST005951_2	Body mass index	9.000000e-09
GCST007840_3	Low HDL-cholesterol levels	6.000000e-12
GCST009264_13	Thalamus volume	5.000000e-06
GCST90011894_11	Retinitis pigmentosa	8.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006782	cups of coffee per day measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0006935	thalamus volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, decreases reaction, affects methylation	3
Nickel	decreases expression, increases expression	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
Tretinoin	decreases reaction, increases expression	3
Air Pollutants	decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Poly I-C	increases expression	2
Silicon Dioxide	increases expression	2
Smoke	increases abundance, increases expression, decreases expression	2
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
chlorophyllin	decreases reaction, increases expression	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, decreases expression, affects localization	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
2’,5’-oligoadenylate	affects binding, increases activity, increases expression	1
hydroquinone	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	decreases reaction, increases expression	1
7,7’-dimethoxy-(4,4’-bi-1,3-benzodioxole)-5,5’-dicarboxylic acid dimethyl ester	increases expression	1
epigallocatechin gallate	decreases expression	1
pentanal	increases expression	1
S-1,2-dichlorovinyl-N-acetylcysteine	affects expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
Am 580	increases expression, decreases reaction	1
Ro 41-5253	decreases reaction, increases expression	1
CGP 52608	increases reaction, affects binding	1
monomethylarsonous acid	decreases expression	1
tofacitinib	decreases expression	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1GQ	Abcam A-549 OAS2 KO 1	Cancer cell line	Male
CVCL_B1GR	Abcam A-549 OAS2 KO 3	Cancer cell line	Male
CVCL_B2P9	Abcam A-549 OAS2 KO 2	Cancer cell line	Male

Clinical trials (associated diseases)

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