DIS3 Gene (DIS3 Homolog, Exosome Endoribonuclease and 3'-5' Exoribonuclease)
A critical component of the RNA exosome complex involved in RNA processing and degradation; mutations are linked to multiple myeloma and other cancers.
Gene Information Card
| Symbol | DIS3 |
|---|---|
| Full Name | DIS3 homolog, exosome endoribonuclease and 3'-5' exoribonuclease |
| Gene Type | Protein coding |
| Chromosomal Location | 13q22.1 |
| NCBI Gene ID | 22894 ncbi.nlm.nih.gov/gene/22894 |
| Ensembl ID | ENSG00000100320 |
| UniProt ID | Q9Y2L1 |
| OMIM ID | 607533 |
| HGNC ID | 20604 |
| Aliases | KIAA1008, EXOSC11, RRP44, DIS3P1 |
Description
DIS3 encodes a catalytic subunit of the RNA exosome complex, possessing both endoribonuclease and 3'-5' exoribonuclease activities. It is essential for processing and degradation of various RNA species, including ribosomal RNA, messenger RNA, and non-coding RNAs. The gene is located on chromosome 13q22.1 and is frequently mutated in multiple myeloma, where loss-of-function mutations contribute to genomic instability and tumorigenesis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Multiple Myeloma | Loss-of-function mutations in DIS3 impair RNA exosome activity, leading to aberrant RNA processing and genomic instability. | PMID: 22158538; COSMIC; ClinVar |
| Acute Myeloid Leukemia | Recurrent somatic mutations in DIS3 are observed, suggesting a role in myeloid malignancies through disrupted RNA surveillance. | PMID: 23539503; COSMIC |
| Chronic Lymphocytic Leukemia | Rare DIS3 mutations identified in CLL, potentially affecting RNA metabolism and contributing to disease progression. | PMID: 26014290; COSMIC |
| Breast Cancer | DIS3 mutations reported in breast cancer, though functional impact remains under investigation. | COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 15.2 | Medium |
| Bone Marrow | 10.8 | Medium |
| Spleen | 9.5 | Medium |
| Lymph Node | 8.3 | Medium |
| Brain | 6.1 | Low |
| Liver | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (leukemia) | 12.3 | High expression |
| HeLa (cervical) | 9.8 | Medium expression |
| A549 (lung) | 8.5 | Medium expression |
| MCF7 (breast) | 7.2 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Glu665Lys (E665K) | Missense | ~3% in multiple myeloma | Loss of exoribonuclease activity |
| p.Asp488Asn (D488N) | Missense | ~2% in multiple myeloma | Impaired catalytic function |
| p.Arg780* | Nonsense | <1% | Truncation, loss of function |
| p.Leu813Pro (L813P) | Missense | <1% | Structural disruption, reduced activity |
Mutation functional classification
Loss of Function (LOF)
Most DIS3 mutations in multiple myeloma are loss-of-function, reducing or abolishing exoribonuclease activity, leading to RNA processing defects and genomic instability.
Gain of Function (GOF)
No well-characterized gain-of-function mutations have been reported for DIS3.
Dominant Negative (DN)
Some missense mutations (e.g., E665K) may exert a dominant-negative effect by disrupting exosome complex assembly or function.
View complete mutation data：
Gene Ontology (GO)
| • 3'-5' exoribonuclease activity | • endoribonuclease activity |
| • RNA binding | • exosome (RNase complex) |
| • nuclear exosome (RNase complex) | • cytoplasmic exosome (RNase complex) |
| • RNA processing | • rRNA processing |
| • mRNA catabolic process | • nuclear-transcribed mRNA catabolic process |
| • exonucleolytic |
Pathways
• RNA degradation (KEGG: hsa03018)
• Exosome pathway (Reactome: R-HSA-73886)
Protein Summary
DIS3 (RRP44) is a 958-amino-acid protein that serves as the catalytic core of the RNA exosome complex. It contains an N-terminal PIN domain with endoribonuclease activity and a C-terminal RNB domain with processive 3'-5' exoribonuclease activity. The protein is highly conserved and localizes to both the nucleus and cytoplasm, where it participates in RNA surveillance, turnover, and quality control. Loss of DIS3 function is strongly associated with multiple myeloma and other cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DIS3L Knockout HEK293 Cell Line | EDJ-KQ7531 | Human | 115752 | Details Get a Quote |
| DIS3L2 Knockout HEK293 Cell Line | EDJ-KQ8441 | Human | 129563 | Details Get a Quote |
| DIS3L Knockout HCT 116 Cell Line | EDJ-KQ31464 | Human | 115752 | Details Get a Quote |
| DIS3L Knockout A-549 Cell Line | EDJ-KQ32816 | Human | 115752 | Details Get a Quote |
| DIS3L Knockout HeLa Cell Line | EDJ-KQ32818 | Human | 115752 | Details Get a Quote |
| DIS3L2 Knockout A-549 Cell Line | EDJ-KQ35788 | Human | 129563 | Details Get a Quote |
| DIS3L2 Knockout HCT 116 Cell Line | EDJ-KQ35790 | Human | 129563 | Details Get a Quote |
| DIS3L2 Knockout HeLa Cell Line | EDJ-KQ35791 | Human | 129563 | Details Get a Quote |
| DIS3L2 (p.N529=) Point Mutation in HAP1 Cell Line | EDC03450 | Human | 129563 | Details Get a Quote |
