ZNF521
Chr 18zinc finger protein 521
Also known as: EHZF, Evi3
This transcription factor acts as both an activator and repressor depending on context, regulating BMP signaling and hematopoietic system development while also controlling neuronal fate commitment through interactions with other transcription factors like EBF1. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delays. The gene is highly constrained against loss-of-function variants, indicating intolerance to haploinsufficiency.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
192 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 | 33 | 0 | 33 |
Likely Pathogenic | 0 | 0 | 1 | 0 | 1 |
VUS | 0 | 130 | 6 | 0 | 136 |
Likely Benign | 0 | 1 | 1 | 3 | 5 |
Benign | 0 | 0 | 0 | 1 | 1 |
| Total | 0 | 131 | 41 | 4 | 176 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZNF521 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
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 →External Resources
Links to major genomics databases and tools