ZNF658
Chr 9zinc finger protein 658
This gene encodes a zinc-sensitive transcriptional repressor that regulates cellular zinc homeostasis by binding to zinc transcriptional regulatory elements in gene promoters and controls ribosome biogenesis by modulating rRNA and ribosomal protein levels. The gene is extremely intolerant to loss-of-function variants (pLI ~1.0, LOEUF 1.9), suggesting that haploinsufficiency would be highly deleterious, but no established human disease phenotype has been reported to date. Given its critical role in zinc homeostasis and ribosome biogenesis, mutations would likely affect cellular metabolism and protein synthesis.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Tolerant to missense variation
This gene has evidence for multiple mechanisms of pathogenicity (dominant-negative and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to dominant-negative as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
247 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 0 | 0 | 41 | 0 | 41 |
Likely Pathogenic | 0 | 0 | 4 | 0 | 4 |
VUS | 0 | 182 | 1 | 0 | 183 |
Likely Benign | 0 | 12 | 1 | 2 | 15 |
Benign | 0 | 0 | 1 | 0 | 1 |
| Total | 0 | 194 | 48 | 2 | 244 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZNF658 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →No open access results found
External Resources
Links to major genomics databases and tools