RNASEL Gene: Ribonuclease L in Innate Immunity and Prostate Cancer Susceptibility
A comprehensive biomedical overview of RNASEL, its function, associated diseases, expression, mutations, and clinical significance.
Gene Information Card
| Symbol | RNASEL |
|---|---|
| Full Name | Ribonuclease L |
| Gene Type | Protein coding |
| Chromosomal Location | 1q25.3 |
| NCBI Gene ID | 6041 ncbi.nlm.nih.gov/gene/6041 |
| Ensembl ID | ENSG00000137968 |
| UniProt ID | Q05823 |
| OMIM ID | 180435 |
| HGNC ID | 10050 |
| Aliases | PRCA1, RNS4, 2-5A-dependent ribonuclease |
Description
RNASEL encodes ribonuclease L, a key enzyme in the interferon-regulated 2-5A system that degrades viral and cellular RNA to limit viral replication. It also plays roles in apoptosis, cell proliferation, and tumor suppression. Germline mutations in RNASEL are associated with hereditary prostate cancer 1 (HPC1) and increased susceptibility to prostate cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Prostate cancer (hereditary, HPC1) | Loss-of-function mutations reduce RNase L activity, impairing antiviral and pro-apoptotic functions, potentially allowing oncogenic viral infections or unchecked cell proliferation. | ClinVar, OMIM, COSMIC |
| Prostate cancer (sporadic) | Reduced RNase L expression or activity due to polymorphic variants (e.g., R462Q) may increase susceptibility to viral triggers and genomic instability. | ClinVar, COSMIC |
| Chronic fatigue syndrome (CFS) (controversial) | RNase L pathway dysregulation, including altered 2-5A binding and cleavage products, has been reported in some CFS patients, though causality is debated. | UniProt, literature (not in primary databases) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Prostate | 9.2 | Medium |
| Spleen | 7.8 | Medium |
| Lung | 6.5 | Low |
| Liver | 5.1 | Low |
| Kidney | 4.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| PC-3 (prostate cancer) | 12.5 | High expression; used in functional studies |
| MCF7 (breast cancer) | 8.0 | Moderate expression |
| HeLa (cervical cancer) | 7.2 | Moderate expression |
| A549 (lung cancer) | 6.0 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R462Q (rs486907) | Missense | ~13% allele frequency in some populations | Reduces enzymatic activity; associated with increased prostate cancer risk |
| M1I (rs12757998) | Missense | ~5% allele frequency | Potential loss of function; reported in prostate cancer cases |
| 471delAAAG | Frameshift | Rare | Premature truncation; loss of function; linked to HPC1 |
| E265X | Nonsense | Rare | Truncated protein; loss of function; found in prostate cancer families |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations (e.g., frameshift, nonsense, and some missense) reduce or abolish ribonuclease activity, impairing antiviral defense and apoptosis.
Gain of Function (GOF)
No gain-of-function mutations have been reported; all known pathogenic variants are loss-of-function.
Dominant Negative (DN)
Some missense variants (e.g., R462Q) may exert a dominant-negative effect by forming inactive dimers with wild-type protein, reducing overall activity.
View complete mutation data：
Gene Ontology (GO)
| • ribonuclease activity | • 2-5A binding |
| • RNA binding | • endoribonuclease activity |
| • protein homodimerization activity | • zinc ion binding |
| • innate immune response | • apoptotic process |
| • response to virus | • mRNA catabolic process |
Pathways
• OAS/RNase L pathway (antiviral innate immunity)
• Interferon signaling
• Apoptosis signaling
• 2-5A system
Protein Summary
RNase L is a 741-amino acid protein with ankyrin repeats, a protein kinase-like domain, and a ribonuclease domain. It exists as a monomer and dimerizes upon binding to 2-5A (oligoadenylates synthesized by OAS enzymes). The activated RNase L cleaves single-stranded RNA, leading to viral RNA degradation and inhibition of protein synthesis. It also induces apoptosis via mitochondrial pathways and modulates cell proliferation. Mutations affecting its catalytic activity are linked to cancer susceptibility.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RNASEL Knockout HEK293T Cell Line | EDJ-KQ160 | Human | 6041 | Details Get a Quote |
| RNASEL Knockout HEK293 Cell Line | EDJ-KQ15093 | Human | 6041 | Details Get a Quote |
| RNASEL Knockout HeLa Cell Line | EDJ-KQ44427 | Human | 6041 | Details Get a Quote |
| RNASEL Knockout A-549 Cell Line | EDJ-KQ45667 | Human | 6041 | Details Get a Quote |
| RNASEL Knockout HCT 116 Cell Line | EDJ-KQ45668 | Human | 6041 | Details Get a Quote |
