XRN2
Chr 205'-3' exoribonuclease 2
The protein encoded by this gene is a 5'-3' exoribonuclease that promotes transcription termination by RNA polymerase II through degradation of cleaved RNA fragments. Biallelic pathogenic variants cause Chudley-McCullough syndrome, an autosomal recessive disorder characterized by early-onset sensorineural hearing loss and brain malformations including hydrocephalus, agenesis of the corpus callosum, and colpocephaly. The gene is highly constrained against loss-of-function variants (LOEUF 0.355), indicating that such variants are likely to be pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Moderately missense-constrained (top ~2.5%)
ClinVar Variant Classifications
166 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 22 | 0 | 22 |
Likely Pathogenic | 0 | 0 | 3 | 0 | 3 |
VUS | 0 | 85 | 5 | 0 | 90 |
Likely Benign | 0 | 2 | 0 | 0 | 2 |
Benign | 0 | 1 | 0 | 0 | 1 |
| Total | 0 | 88 | 30 | 0 | 118 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
XRN2 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools