XRN2: 5'-3' Exoribonuclease 2
Key regulator of RNA processing, transcription termination, and genome stability
Gene Information Card
| Symbol | XRN2 |
|---|---|
| Full Name | 5'-3' Exoribonuclease 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 20p11.22 |
| NCBI Gene ID | 22803 ncbi.nlm.nih.gov/gene/22803 |
| Ensembl ID | ENSG00000101282 |
| UniProt ID | Q9H0D6 |
| OMIM ID | 606199 |
| HGNC ID | 12841 |
| Aliases | DHM1, DHP1, RAT1, RNH2 |
Description
XRN2 encodes a 5'-3' exoribonuclease that degrades RNA substrates from the 5' end, playing essential roles in RNA metabolism including transcription termination by RNA polymerase II, processing of ribosomal RNA, and decay of defective mRNAs. The enzyme is involved in the torpedo model of transcription termination, where it degrades the nascent transcript after cleavage by the polyadenylation machinery. XRN2 also contributes to genome stability by resolving R-loops and preventing DNA damage.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (multiple types) | XRN2 mutations or altered expression disrupt RNA processing and transcription termination, leading to aberrant gene expression and genomic instability. | COSMIC; PMID: 23582326 |
| Neurodevelopmental disorders | Loss-of-function variants impair RNA surveillance and neuronal gene expression. | ClinVar; PMID: 27545674 |
| Pulmonary fibrosis | Dysregulation of XRN2-mediated RNA decay contributes to fibrotic pathways. | PMID: 31358969 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | High |
| Lymph node | 10.8 | Medium |
| Brain (cortex) | 8.5 | Medium |
| Liver | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 12.4 | Cervical cancer cell line |
| HEK293 | 11.0 | Embryonic kidney cells |
| K562 | 9.8 | Leukemia cell line |
| HepG2 | 7.2 | Hepatocellular carcinoma |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; truncated protein |
| c.567_568del (p.Glu190fs) | Frameshift | <0.1% | Loss of function; premature stop |
| c.890A>G (p.Tyr297Cys) | Missense | 0.2% | Unknown; predicted damaging |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations that truncate the protein or disrupt the catalytic domain lead to loss of exoribonuclease activity, impairing RNA decay and transcription termination.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in XRN2.
Dominant Negative (DN)
Not established; XRN2 functions as a monomer, and dominant-negative effects have not been documented.
View complete mutation data：
Gene Ontology (GO)
| • 5'-3' exoribonuclease activity | • RNA binding |
| • nucleic acid binding | • nucleus |
| • cytoplasm | • transcription termination by RNA polymerase II |
| • RNA catabolic process | • rRNA processing |
| • mRNA catabolic process |
Pathways
• RNA polymerase II transcription termination
• mRNA surveillance pathway
• rRNA processing in the nucleus and cytosol
Protein Summary
XRN2 is a 950-amino acid protein with a conserved 5'-3' exoribonuclease domain. It localizes to the nucleus and cytoplasm, where it degrades RNA substrates processively from the 5' end. The protein interacts with the nuclear exosome and other RNA processing factors to ensure proper termination of transcription and clearance of aberrant RNAs. Structural studies reveal a toroidal shape with a central channel that accommodates single-stranded RNA.
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