ZNF598
protein-codingzinc finger protein 598, E3 ubiquitin ligase, the group of Zinc fingers C2H2-type|Ring finger proteins
Gene summary
Zinc-finger proteins bind nucleic acids and play important roles in various cellular functions, including cell proliferation, differentiation, and apoptosis. This protein and Grb10-interacting GYF protein 2 have been identified as a components of the mammalian 4EHP (m4EHP) complex. The complex is thought to function as a translation repressor in embryonic development. [provided by RefSeq, Oct 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~12.2 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZNF598 variants in ClinVar
No annotated ClinVar phenotypes.
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript . Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | ||||
| missense | 44 | 3 | 47 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 44 | 5 | 0 | 49 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001392593.1 | 14 | Standard | |
| RefSeq | NP_001392594.1 | 14 | Standard | |
| RefSeq | NP_835461.2 | 14 | Standard | |
| Ensembl | ENSP00000455308.2 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- protein monoubiquitination
- protein ubiquitination
- rescue of stalled ribosome
Molecular Function
- RNA binding
- protein binding
- ribosome binding
- metal ion binding
- ubiquitin protein ligase activity
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000431526
- Coding exons
- 14
- Length
- 12170
- Individuals with no LoFs
- 124397
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 124404
- p
- 0.0000281
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | -0.924 | 590 | 530 | 1.11 | 0.0000373 | 5726 |
| Missense (PolyPhen) | 182 | 209.06 | 0.87055 | 2364 | ||
| Synonymous | -4.48 | 319 | 232 | 1.37 | 0.0000175 | 1804 |
| Loss of Function | 4.19 | 7 | 32.9 | 0.213 | 0.00000165 | 393 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000038 | 0.000036 | rare |
| South Asian | 0.00017 | 0.000098 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 ubiquitin-protein ligase that plays a key role in the ribosome quality control (RQC), a pathway that takes place when a ribosome has stalled during translation (PubMed:28065601, PubMed:28132843). Required for ribosomes to terminally stall during translation of poly(A) sequences by mediating monoubiquitination of 40S ribosomal protein RPS10/eS10, RPS20/uS10 and RPS3/uS3 (PubMed:28065601, PubMed:28132843). Stalling precludes synthesis of a long poly-lysine tail and initiates the RQC pathway to degrade the potentially detrimental aberrant nascent polypeptide (PubMed:28065601, PubMed:28132843). Also acts as a component of the 4EHP-GYF2 complex, a multiprotein complex that acts as a repressor of translation initiation (PubMed:22751931). {ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:28065601, ECO:0000269|PubMed:28132843}.;
Essentials
- Essential (CRISPR2)
- S
- Indispensability pred.
- N
- Indispensability score
- 0.367
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |