ISG20

Chr 15

interferon stimulated exonuclease gene 20

Also known as: CD25, HEM45

NCBI Gene: 3669 ENSG00000172183 UniProt: Q96AZ6

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.

ResearchSummary from RefSeq, UniProt

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]

ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.69

LOEUF

Mechanism· predicted

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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

Background carrier burden — how many people carry a rare variant somewhere in ISG20?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 170

264 rare PASS variants

Rare truncating (LoF)

1 in 4,500

42 rare PASS variants

Rare synonymous (reference)

1 in 580

115 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for ISG20. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 240	1 in 4,400
South Asian	~43k	1 in 280	1 in 5,400
Remaining (unassigned)	~30k	1 in 250	1 in 2,700
European (Finnish)	~27k	1 in 1,300	none seen
Admixed American	~22k	1 in 220	1 in 1,100
African / African American	~21k	1 in 200	1 in 3,500
East Asian	~20k	1 in 190	none seen
Ashkenazi Jewish	~13k	1 in 820	≈ 1 in 6,500
Middle Eastern	~2,884	1 in 170	≈ 1 in 2,900

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓