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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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XRN2
5'-3' exoribonuclease 2
Chromosome 20 · 20p11.22
NCBI Gene: 22803Ensembl: ENSG00000088930.9HGNC: HGNC:12836UniProt: B4DZC3
238PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
membranetermination of RNA polymerase II transcriptiontranscription termination site sequence-specific DNA bindingspermatogenesisattention deficit hyperactivity disorderatrial fibrillationneurodegenerative diseaseautism
✦AI Summary

XRN2 is a nuclear 5'→3' exoribonuclease that plays multifaceted roles in RNA processing and transcription termination 1. Its primary function involves processively degrading single-stranded RNA with 5'-terminal monophosphates to mononucleotides 1. During transcription termination, XRN2 executes the "torpedo" mechanism, whereby cleavage at polyadenylation sites generates a 5'-end on the nascent transcript that recruits XRN2, enabling it to degrade the 3' fragment tethered to RNA polymerase II and thereby dislodging the polymerase 23. XRN2 also participates in R-loop resolution through functional cooperation with the HELQ helicase, where HELQ unwinds R-loops while XRN2 degrades the exposed RNA strand 4. At transcription termination regions, XRN2 functions downstream of the DDX21-METTL3 co-transcriptional m6A modification axis, promoting proper termination and genome stability 5. RNF8-mediated ubiquitylation facilitates XRN2 recruitment to R-loop-prone loci, preventing R-loop accumulation and genomic instability 6. Beyond transcription regulation, XRN2 functions in rRNA and snoRNA maturation 1, Polycomb-mediated heterochromatin silencing 7, and glioblastoma cell motility and invasion 8. Elevated XRN2 expression in glioblastomas correlates with poor patient survival, suggesting clinical relevance as a therapeutic target 8.

Sources cited
1
XRN2 is a conserved nuclear 5'→3' exoribonuclease that processively degrades single-stranded RNA and functions in pre-mRNA, rRNA, and snoRNA processing
PMID: 23863139
2
XRN2 executes the torpedo mechanism of transcription termination by degrading the 3' RNA fragment after polyadenylation-site cleavage, dislodging RNAPII
PMID: 39496457
3
XRN2 (Rat1-Rai1 homolog) greatly stimulates transcription termination at T-tract containing sequences and loads onto newly exposed 5' RNA ends
PMID: 37683646
4
XRN2 cooperates with HELQ helicase in R-loop resolution, coordinating RNA digestion with R-loop unwinding
PMID: 39965657
5
XRN2-mediated termination functions downstream of the DDX21-METTL3 co-transcriptional m6A modification nexus at transcription termination regions
PMID: 38569554
6
RNF8 ubiquitylates XRN2 to facilitate its recruitment to R-loop-prone loci, preventing R-loop accumulation and genomic instability
PMID: 37697435
7
XRN2 exoribonuclease activity is required downstream of the rixosome for Polycomb-mediated silencing of target genes
PMID: 35355014
8
XRN2 is required for glioblastoma cell motility and invasion; elevated XRN2 expression correlates with poor patient survival
PMID: 35563787
Disease Associationsⓘ20
attention deficit hyperactivity disorderOpen Targets
0.37Weak
atrial fibrillationOpen Targets
0.34Weak
neurodegenerative diseaseOpen Targets
0.33Weak
autismOpen Targets
0.30Weak
autism spectrum disorderOpen Targets
0.25Weak
adolescent idiopathic scoliosisOpen Targets
0.22Weak
food allergyOpen Targets
0.22Weak
insomniaOpen Targets
0.22Weak
risk-taking behaviourOpen Targets
0.15Weak
oligodendrogliomaOpen Targets
0.09Suggestive
cardiac arrhythmiaOpen Targets
0.08Suggestive
non-small cell lung carcinomaOpen Targets
0.08Suggestive
glioblastoma multiformeOpen Targets
0.08Suggestive
cancerOpen Targets
0.08Suggestive
atrial flutterOpen Targets
0.07Suggestive
chronic obstructive pulmonary diseaseOpen Targets
0.06Suggestive
Abnormality of the skeletal systemOpen Targets
0.06Suggestive
neoplasmOpen Targets
0.04Suggestive
oral squamous cell carcinomaOpen Targets
0.04Suggestive
ovarian neoplasmOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
DCP2Protein interaction100%DCP1AProtein interaction100%MTREXProtein interaction100%CPSF3Protein interaction99%DXOProtein interaction99%NKRFProtein interaction98%
Tissue Expression6 tissues
Bone Marrow
100%
Lung
91%
Ovary
70%
Heart
63%
Brain
62%
Liver
56%
Gene Interaction Network
Click a node to explore
XRN2DCP2DCP1AMTREXCPSF3DXONKRF
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q9H0D6
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.41Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.32 [0.25–0.41]
RankingsWhere XRN2 stands among ~20K protein-coding genes
  • #1,659of 20,598
    Most Researched238 · top 10%
  • #2,138of 17,882
    Most Constrained (LOEUF)0.41 · top quartile
Genes detectedXRN2
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
DDX21 mediates co-transcriptional RNA m
PMID: 38569554
Mol Cell · 2024
1.00
2
The human HELQ helicase and XRN2 exoribonuclease cooperate in R-loop resolution.
PMID: 39965657
Open Biol · 2025
0.90
3
The multifunctional RNase XRN2.
PMID: 23863139
Biochem Soc Trans · 2013
0.80
4
RNF8 ubiquitylation of XRN2 facilitates R-loop resolution and restrains genomic instability in BRCA1 mutant cells.
PMID: 37697435
Nucleic Acids Res · 2023
0.70
5
A novel splice variant of human XRN2 gene is mainly expressed in blood leukocyte.
PMID: 16147866
DNA Seq · 2005
0.64