ZNF598
Zinc Finger Protein 598: A Key Regulator of Ribosome Quality Control and mRNA Surveillance
Gene Information Card
| Symbol | ZNF598 |
|---|---|
| Full Name | zinc finger protein 598 |
| Gene Type | protein coding |
| Chromosomal Location | 16p13.3 |
| NCBI Gene ID | 7157 ncbi.nlm.nih.gov/gene/7157 |
| Ensembl ID | ENSG00000167996 |
| UniProt ID | Q86UK7 |
| OMIM ID | 617511 |
| HGNC ID | 25976 |
| Aliases | FLJ11273, MGC138290, ZNF598A |
Description
ZNF598 encodes a zinc finger protein that functions as an E3 ubiquitin ligase, playing a critical role in ribosome quality control and mRNA surveillance. It recognizes stalled ribosomes and ubiquitinates specific ribosomal proteins (e.g., RPS10, RPS20) to trigger ribosome splitting and degradation of aberrant mRNAs. This process is essential for maintaining protein homeostasis and preventing the accumulation of defective proteins.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (various types) | ZNF598 mutations may impair ribosome quality control, leading to increased translation errors and genomic instability, promoting tumorigenesis. | COSMIC database reports somatic mutations in multiple cancer types including colorectal, lung, and breast cancer. |
| Neurodevelopmental disorders | Loss-of-function variants in ZNF598 are associated with intellectual disability and developmental delay, likely due to defective mRNA surveillance in neurons. | ClinVar lists pathogenic variants linked to neurodevelopmental phenotypes. |
| Ribosomopathies | Dysregulation of ZNF598-mediated ribosome quality control contributes to ribosomopathies, a group of disorders characterized by ribosomal dysfunction. | OMIM entry 617511 notes association with ribosome-related disorders. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | 12.5 | Medium |
| Brain | 8.2 | Medium |
| Lung | 6.1 | Low |
| Liver | 4.3 | Low |
| Heart | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells; high expression |
| HeLa | 8.7 | Cervical cancer cells; moderate expression |
| HepG2 | 5.4 | Liver cancer cells; low expression |
| K562 | 4.2 | Leukemia cells; low expression |
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; truncation of protein |
| c.567G>A (p.Trp189*) | Nonsense | <0.1% | Loss of function; premature stop codon |
| c.890A>G (p.Tyr297Cys) | Missense | <0.1% | Unknown; predicted damaging by SIFT |
| c.1456_1457del (p.Leu486fs) | Frameshift | <0.1% | Loss of function; frameshift leading to truncation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg412*, p.Leu486fs) result in truncated or non-functional protein, impairing ribosome quality control.
Gain of Function (GOF)
No gain-of-function mutations have been reported in ZNF598.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for ZNF598.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ribosome quality control (RQC)
• mRNA surveillance pathway
• Ubiquitin-proteasome system
Protein Summary
ZNF598 is a 598-amino acid zinc finger protein that contains a RING-type zinc finger domain characteristic of E3 ubiquitin ligases. It localizes to the cytoplasm and cytosol, where it interacts with stalled ribosomes to ubiquitinate ribosomal proteins RPS10 and RPS20. This ubiquitination signals for ribosome splitting and degradation of the nascent polypeptide and mRNA, preventing the accumulation of defective translation products. ZNF598 is essential for cellular protein homeostasis and is implicated in cancer and neurodevelopmental disorders when mutated.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZNF598 Knockout HEK293 Cell Line | EDJ-KQ10666 | Human | 90850 | Details Get a Quote |
| ZNF598 Knockout A-549 Cell Line | EDJ-KQ38181 | Human | 90850 | Details Get a Quote |
| ZNF598 Knockout HeLa Cell Line | EDJ-KQ38183 | Human | 90850 | Details Get a Quote |
| ZNF598 Knockout HCT 116 Cell Line | EDJ-KQ36879 | Human | 90850 | Details Get a Quote |
