ISG20: Interferon-Stimulated Exonuclease Gene 20 - Structure, Function, and Clinical Significance
A comprehensive biomedical overview of ISG20, an interferon-induced 3'→5' exonuclease involved in antiviral immunity and RNA metabolism, with curated data from authoritative databases.
Gene Information Card
| Symbol | ISG20 |
|---|---|
| Full Name | Interferon Stimulated Exonuclease Gene 20 |
| Gene Type | Protein coding |
| Chromosomal Location | 15q26.3 |
| NCBI Gene ID | 3669 ncbi.nlm.nih.gov/gene/3669 |
| Ensembl ID | ENSG00000172183 |
| UniProt ID | Q9Y2Z4 |
| OMIM ID | 604533 |
| HGNC ID | 6130 |
| Aliases | CDAM; DKFZp686J15120 |
Description
ISG20 encodes an interferon-stimulated 3'→5' exonuclease that plays a critical role in antiviral defense by degrading viral RNA. It is induced by type I interferons and participates in RNA metabolism, including the processing of ribosomal RNA and small nucleolar RNAs. The protein localizes to the nucleus and cytoplasm, and its expression is upregulated in response to viral infections and immune activation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatitis C Virus Infection | ISG20 expression is induced by interferon treatment and contributes to antiviral activity by degrading HCV RNA. | Evidence from in vitro studies and clinical observations (PubMed: 14512541, 2003). |
| Influenza A Virus Infection | ISG20 restricts influenza virus replication by degrading viral RNA in an interferon-dependent manner. | Experimental evidence in cell culture (PubMed: 21775446, 2011). |
| HIV-1 Infection | ISG20 inhibits HIV-1 replication by degrading viral RNA, and its expression is upregulated in response to interferon. | In vitro studies (PubMed: 18032424, 2007). |
| Cancer (Various) | ISG20 expression is altered in certain cancers, potentially affecting tumor progression through RNA metabolism and immune modulation. | Expression data from TCGA and literature (PubMed: 25691820, 2015). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.3 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.5 | Low |
| Lung | 6.2 | Low |
| Liver | 4.1 | Low |
| Kidney | 3.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | High expression; responsive to interferon stimulation |
| A549 | 12.7 | High expression; inducible by interferons |
| HepG2 | 8.9 | Moderate expression; upregulated upon viral infection |
| K562 | 5.4 | Low expression; minimal basal activity |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1Val) | Missense | Rare (MAF <0.01) | Potential loss of start codon, affecting protein translation |
| c.245C>T (p.Pro82Leu) | Missense | Rare (MAF <0.01) | May affect exonuclease activity; not well characterized |
| c.398G>A (p.Arg133His) | Missense | Rare (MAF <0.01) | Located in catalytic domain; potential functional impact |
Mutation functional classification
Loss of Function (LOF)
Mutations that disrupt the exonuclease active site or protein stability are predicted to impair RNA degradation, leading to reduced antiviral activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported; overexpression of wild-type ISG20 enhances antiviral effects.
Dominant Negative (DN)
No dominant-negative mutations have been described; however, mutations affecting dimerization could theoretically interfere with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • 3'-5' exonuclease activity | • RNA binding |
| • nucleic acid binding | • nucleus |
| • cytoplasm | • interferon-gamma-mediated signaling pathway |
| • defense response to virus | • RNA catabolic process |
Pathways
• Interferon signaling
• Antiviral mechanism by IFN-stimulated genes
• RNA degradation
Protein Summary
ISG20 is a 20 kDa protein consisting of 181 amino acids. It belongs to the DEDD family of 3'→5' exonucleases, characterized by four conserved acidic residues (Asp, Glu, Asp, Asp) essential for catalytic activity. The protein forms homodimers and localizes to both the nucleus and cytoplasm. It exhibits processive 3'→5' exonuclease activity on single-stranded RNA, with a preference for viral RNA. ISG20 is induced by type I and type II interferons, and its expression is regulated by IRF-1 and STAT1. It plays a role in the degradation of viral RNA, thereby limiting viral replication. Additionally, ISG20 is involved in the processing of ribosomal RNA and small nucleolar RNAs, suggesting a broader role in RNA metabolism.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ISG20 Knockout HEK293 Cell Line | EDJ-KQ5006 | Human | 3669 | Details Get a Quote |
| ISG20 Knockout A-549 Cell Line | EDJ-KQ27911 | Human | 3669 | Details Get a Quote |
| ISG20 Knockout HCT 116 Cell Line | EDJ-KQ27912 | Human | 3669 | Details Get a Quote |
| ISG20 Knockout HeLa Cell Line | EDJ-KQ27913 | Human | 3669 | Details Get a Quote |
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