ISG20

Chr 15

interferon stimulated exonuclease gene 20

Also known as: CD25, HEM45

NCBI Gene: 3669 ENSG00000172183 UniProt: Q96AZ6 OMIM: 604533

ISG20 encodes an interferon-induced antiviral exoribonuclease that degrades single-stranded RNA and inhibits viral genome replication and translation. The gene shows low constraint against loss-of-function variants (pLI 0.003, LOEUF 1.69), and no established Mendelian disease associations have been reported in the provided data. This protein functions as part of the innate immune response against RNA viruses and may also contribute to ribosome biogenesis.

OMIM ResearchSummary from RefSeq, UniProt

Enables 3'-5' exonuclease activity and RNA binding activity. Involved in defense response to virus; negative regulation of viral genome replication; and nucleobase-containing compound catabolic process. Located in cytoplasm and nuclear lumen. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

DNmechanismLOEUF 1.69

Clinical Summary— ISG20

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

34 VUS of 46 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.69LOEUF

pLI 0.003

Z-score 0.39

OE 0.81 (0.39–1.69)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.21Z-score

OE missense 0.95 (0.81–1.10)

119 obs / 125.7 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.81 (0.39–1.69)

0≤0.351.4

Missense OE?0.95 (0.81–1.10)

0≤0.61.4

Synonymous OE?1.07

0≤1.21.6

LoF obs/exp: 4 / 4.9Missense obs/exp: 119 / 125.7Syn Z: -0.40

This gene — mechanism propensity

0.6938th %ile

GOF

0.5955th %ile

LOF

0.2873th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

46 submitted variants in ClinVar

ClinVar

Classification Summary

VUS34

Likely Benign3

Benign5

VUS

Likely Benign

Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	Missense + Inframe	Synonymous	Total
Pathogenic	0	0	0
Likely Pathogenic	0	0	0
VUS	34	0	34
Likely Benign	1	2	3
Benign	1	4	5
Total	36	6	42

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

33 pathogenic / likely-pathogenic (of 36) ClinVar copy-number / structural variants overlap ISG20 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →