OAS1

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

Basic information

Region (hg38): 12:112905856-112933219

Previous symbols: [ "OIAS" ]

Links

ENSG00000089127 ∙ NCBI:4938 ∙ OMIM:164350 ∙ HGNC:8086 ∙ Uniprot:P00973 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pulmonary alveolar proteinosis with hypogammaglobulinemia (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 100 with pulmonary alveolar proteinosis and hypogammaglobulinemia	AD	Allergy/Immunology/Infectious; Pulmonary	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	Allergy/Immunology/Infectious; Pulmonary	29185156; 29455859; 34145065

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the OAS1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the OAS1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	51	4	56
missense			129	22	13	164
nonsense			5	1		6
start loss			1			1
frameshift			6	1	1	8
inframe indel			1			1
splice donor/acceptor (+/-2bp)			3			3
splice region			4	2	2	8
non coding			2	16	12	30
Total	0	0	148	91	30

Variants in OAS1

This is a list of pathogenic ClinVar variants found in the OAS1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-112906823-G-A			Benign (May 13, 2021)
12-112907040-A-G			Uncertain significance (Apr 12, 2023)
12-112907044-T-C			Uncertain significance (Oct 07, 2022)
12-112907047-A-G			Uncertain significance (Jul 25, 2022)
12-112907051-C-G			Likely benign (Dec 02, 2023)
12-112907057-T-C			Likely benign (Oct 07, 2022)
12-112907061-C-G			Uncertain significance (Nov 04, 2023)
12-112907066-C-T			Likely benign (Nov 03, 2020)
12-112907071-C-A			Uncertain significance (Nov 29, 2022)
12-112907077-AC-A			Uncertain significance (Sep 23, 2023)
12-112907078-C-CCCA			Uncertain significance (Jul 17, 2021)
12-112907092-A-G		OAS1-related disorder	Uncertain significance (Jan 08, 2024)
12-112907097-C-T			Uncertain significance (Dec 20, 2023)
12-112907099-C-G			Likely benign (Dec 05, 2022)
12-112907102-G-A			Likely benign (Mar 10, 2023)
12-112907104-C-T			Uncertain significance (Nov 01, 2022)
12-112907109-A-C		not specified	Uncertain significance (Mar 30, 2024)
12-112907117-C-T			Likely benign (Jan 08, 2021)
12-112907118-C-T			Uncertain significance (Aug 22, 2023)
12-112907119-G-A			Uncertain significance (Jan 04, 2024)
12-112907119-G-T			Uncertain significance (May 02, 2023)
12-112907125-A-G			Likely benign (Jan 08, 2024)
12-112907135-T-C			Likely benign (May 15, 2018)
12-112907141-T-C			Likely benign (Mar 08, 2023)
12-112907152-G-A		not specified	Uncertain significance (May 28, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
OAS1	protein_coding	protein_coding	ENST00000445409	6	25409

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000345	0.950	125659	0	89	125748	0.000354

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.426	247	229	1.08	0.0000124	2697
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00104	0.00104
Ashkenazi Jewish	0.0000993	0.0000992
East Asian	0.00207	0.00207
Finnish	0.000370	0.000370
European (Non-Finnish)	0.000123	0.000123
Middle Eastern	0.00207	0.00207
South Asian	0.0000980	0.0000980
Other	0.000815	0.000815

dbNSFP

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}.
• Pathway: 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);The human immune response to tuberculosis;Type II interferon signaling (IFNG);Cytokine Signaling in Immune system;Immune System;Interferon gamma signaling;Interferon alpha/beta signaling;Interferon Signaling (Consensus)

Recessive Scores

• pRec: 0.190

Intolerance Scores

• loftool: 0.979
• rvis_EVS: 1.31
• rvis_percentile_EVS: 94.04

Haploinsufficiency Scores

• pHI: 0.0239
• hipred: N
• hipred_score: 0.145
• ghis: 0.479

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.613

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Oas1h

Gene ontology

• Biological process: glucose metabolic process;response to virus;glucose homeostasis;negative regulation of viral genome replication;defense response to virus;interferon-gamma-mediated signaling pathway;type I interferon signaling pathway;regulation of ribonuclease activity
• Cellular component: extracellular region;nucleus;nucleoplasm;cytoplasm;mitochondrion;endoplasmic reticulum;cytosol
• Molecular function: 2'-5'-oligoadenylate synthetase activity;double-stranded RNA binding;protein binding;ATP binding;metal ion binding