ZEB2
Chr 2ADzinc finger E-box binding homeobox 2
Also known as: HSPC082, SIP-1, SIP1, SMADIP1, ZFHX1B
The encoded protein is a DNA-binding transcriptional repressor that interacts with activated SMADs and localizes to the nucleus. Loss-of-function mutations cause Mowat-Wilson syndrome through an autosomal dominant inheritance pattern. The gene is highly intolerant to loss-of-function variation, consistent with haploinsufficiency as the disease mechanism.
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%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ZEB2 · 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
Nirogacestat in Patients With Kaposi Sarcoma
NOT YET RECRUITINGExpression of Epithelial-Mesenchymal Transition Associated Markers in Peri-implant Tissues
RECRUITINGOral Health, Dento-facial Condition and OHRQoL in Subjects With Mowat-Wilson Syndrome: an Epidemiologic Study.
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools