ZNF598

Chr 16

zinc finger protein 598, E3 ubiquitin ligase

Also known as: HEL2

NCBI Gene: 90850ENSG00000167962UniProt: Q86UK7

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]

143
ClinVar variants
44
Pathogenic / LP
0.55
pLI score
0
Active trials
Clinical Summary— ZNF598
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.55) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
44 Pathogenic / Likely Pathogenic· 91 VUS of 143 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.40LOEUF
pLI 0.548
Z-score 4.19
OE 0.21 (0.12–0.40)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.92Z-score
OE missense 1.11 (1.04–1.19)
590 obs / 530.1 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.21 (0.12–0.40)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.11 (1.04–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.37
0≤1.21.6
LoF obs/exp: 7 / 32.9Missense obs/exp: 590 / 530.1Syn Z: -4.48

ClinVar Variant Classifications

143 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic43
Likely Pathogenic1
VUS91
Likely Benign7
Benign1
43
Pathogenic
1
Likely Pathogenic
91
VUS
7
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
43
0
43
Likely Pathogenic
0
0
1
0
1
VUS
0
75
16
0
91
Likely Benign
0
5
0
2
7
Benign
0
0
1
0
1
Total080612143

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ZNF598 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Single-protein/RNA imaging reveals ZNF598 as a limiting factor in resolving collided ribosomes.
De La Cruz AC et al.·EMBO J
2025🔓 Open Access
Translation of zinc finger domains induces ribosome collision and Znf598-dependent mRNA decay in zebrafish.
Ishibashi K et al.·PLoS Biol
2024🔓 Open AccessFunctional
Ribosomal collision is not a prerequisite for ZNF598-mediated ribosome ubiquitination and disassembly of ribosomal complexes by ASCC.
Miścicka A et al.·Nucleic Acids Res
2024🔓 Open Access
Stalled translation by mitochondrial stress upregulates a CNOT4-ZNF598 ribosomal quality control pathway important for tissue homeostasis.
Geng J et al.·Nat Commun
2024🔓 Open Access
Znf598-mediated Rps10/eS10 ubiquitination contributes to the ribosome ubiquitination dynamics during zebrafish development.
Ugajin N et al.·RNA
2023🔓 Open AccessFunctional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools