ISG20
protein-codinginterferon stimulated exonuclease gene 20, the group of Exonucleases
Gene summary
Enables 3'-5' exonuclease activity and RNA binding activity. Involved in several processes, including DNA catabolic process; defense response to virus; and negative regulation of viral genome replication. Located in cytoplasm and nuclear lumen. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~20.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ISG20 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_002201.6. 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 | 2 | 4 | 6 | |||
| missense | 37 | 1 | 1 | 39 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 37 | 3 | 5 | 45 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_002192.2 | 3 | MANE Select | |
| Ensembl | ENSP00000306565.5 | 3 | MANE Select | |
| RefSeq | NP_001290162.1 | 3 | Standard | |
| RefSeq | NP_001290163.1 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cytokine Signaling in Immune system
- Immune System
- Interferon alpha/beta signaling
- Interferon Signaling
Biological Process
- DNA catabolic process, exonucleolytic
- rRNA processing
- RNA catabolic process
- cell population proliferation
- response to virus
Molecular Function
- 3'-5'-exoribonuclease activity
- exonuclease activity
- single-stranded DNA 3'-5' exodeoxyribonuclease activity
- exoribonuclease II activity
- U1 snRNA binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
- Cajal body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000306072
- Coding exons
- 3
- Length
- 20331
- Individuals with no LoFs
- 125717
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 22
- Defined
- 125739
- p
- 0.0000875
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.212 | 119 | 126 | 0.947 | 0.00000848 | 1163 |
| Missense (PolyPhen) | 37 | 46.389 | 0.79761 | 413 | ||
| Synonymous | -0.400 | 56 | 52.3 | 1.07 | 0.00000344 | 391 |
| Loss of Function | 0.394 | 4 | 4.95 | 0.809 | 2.10e-7 | 57 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00044 | 0.00043 | rare |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000090 | 0.0000088 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Interferon-induced antiviral exoribonuclease that acts on single-stranded RNA and also has minor activity towards single- stranded DNA. Exhibits antiviral activity against RNA viruses including hepatitis C virus (HCV), hepatitis A virus (HAV) and yellow fever virus (YFV) in an exonuclease-dependent manner. May also play additional roles in the maturation of snRNAs and rRNAs, and in ribosome biogenesis. {ECO:0000269|PubMed:11401564, ECO:0000269|PubMed:12594219, ECO:0000269|PubMed:16033969, ECO:0000269|PubMed:21036379}.;
Intolerance Scores
- RVIS EVS
- -0.23
- RVIS percentile EVS
- 36.86
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.866
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |