ZNF462
Chr 9ADzinc finger protein 462
Also known as: WSKA, ZFPIP, Zfp462
This zinc finger transcription factor regulates chromatin structure and controls key developmental genes including SOX2, POU5F1/OCT4, and NANOG, while also regulating neuronal development and neural cell differentiation. Mutations cause Weiss-Kruszka syndrome, an autosomal dominant developmental disorder with intellectual disability, distinctive facial features, and growth abnormalities. The gene is extremely intolerant to loss-of-function variation (pLI >0.99, LOEUF 0.085), indicating that functional copies are critical for normal development.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Among the most LoF-intolerant genes (~top 3%)
Highly missense-constrained (top ~0.1%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
500 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 | 20 | 0 | 3 | 0 | 23 |
Likely Pathogenic | 19 | 0 | 0 | 0 | 19 |
VUS | 3 | 328 | 7 | 1 | 339 |
Likely Benign | 0 | 50 | 1 | 38 | 89 |
Benign | 0 | 2 | 0 | 0 | 2 |
Conflicting | — | 9 | |||
| Total | 42 | 380 | 11 | 39 | 481 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
ZNF462 · 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
External Resources
Links to major genomics databases and tools