XRN1 Gene: Structure, Function, and Clinical Significance
A comprehensive overview of the XRN1 gene, its protein product, associated diseases, expression patterns, and mutations.
Gene Information Card
| Symbol | XRN1 |
|---|---|
| Full Name | 5'-3' exoribonuclease 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 3q23 |
| NCBI Gene ID | 54464 ncbi.nlm.nih.gov/gene/54464 |
| Ensembl ID | ENSG00000169895 |
| UniProt ID | Q8IZH2 |
| OMIM ID | 607994 |
| HGNC ID | 30658 |
| Aliases | DKFZp434H082, hXRN1, SEP1 |
Description
The XRN1 gene encodes a 5'-3' exoribonuclease that plays a critical role in mRNA decay, RNA metabolism, and gene silencing. It is involved in the degradation of cytoplasmic mRNAs after deadenylation and decapping, and also participates in the processing of various RNA species. XRN1 is essential for normal cellular function and has been implicated in several diseases, including cancer and neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | XRN1 mutations or dysregulation lead to altered mRNA stability, affecting oncogene/tumor suppressor expression. | COSMIC database lists somatic mutations in multiple cancer types; studies show altered expression in tumors. |
| Neurodevelopmental disorders | Loss-of-function mutations impair RNA metabolism in neurons, affecting synaptic function. | ClinVar reports pathogenic variants associated with intellectual disability and developmental delay. |
| Viral infections | XRN1 is involved in the degradation of viral RNA, and its inhibition can enhance viral replication. | Research articles demonstrate interaction with viral proteins and modulation of antiviral response. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 25.1 | High |
| Brain | 12.3 | Medium |
| Liver | 8.7 | Medium |
| Heart | 5.2 | Low |
| Lung | 4.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line; high expression |
| HEK293 | 12.8 | Embryonic kidney; moderate expression |
| HepG2 | 9.3 | Liver cancer; moderate expression |
| A549 | 6.1 | Lung cancer; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234A>G (p.Thr412Ala) | Missense | 0.01% (gnomAD) | May affect protein stability; reported in ClinVar as uncertain significance. |
| c.456delC (p.Pro152LeufsTer5) | Frameshift | Rare | Loss-of-function; associated with neurodevelopmental disorder in ClinVar. |
| c.789G>T (p.Glu263Asp) | Missense | 0.005% (gnomAD) | Potential impact on catalytic activity; observed in COSMIC in cancer samples. |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations lead to truncated protein lacking exoribonuclease activity, impairing mRNA decay.
Gain of Function (GOF)
No clear gain-of-function mutations reported; overexpression may occur in some cancers but not due to mutation.
Dominant Negative (DN)
Some missense mutations may produce a protein that interferes with the wild-type enzyme, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • 5'-3' exoribonuclease activity | • RNA binding |
| • mRNA catabolic process | • cytoplasmic processing body |
| • nuclear-transcribed mRNA catabolic process | • deadenylation-dependent decay |
Pathways
• mRNA surveillance pathway
• RNA degradation pathway
• MicroRNA (miRNA) biogenesis and function
Protein Summary
The XRN1 protein is a large (170 kDa) exoribonuclease that degrades RNA in the 5' to 3' direction. It is a key component of the RNA decay machinery, localizing to processing bodies (P-bodies) where it degrades decapped mRNAs. XRN1 also plays roles in RNA interference, antiviral defense, and the regulation of gene expression. Its structure includes a conserved N-terminal catalytic domain and a C-terminal domain involved in protein-protein interactions.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| XRN1 Knockout HAP1 Cell Line | EDJ-KQ78124 | Human | 54464 | Details Get a Quote |
