MIB2
Chr 1MIB E3 ubiquitin protein ligase 2
Also known as: ZZANK1, ZZZ5
The encoded protein is an E3 ubiquitin-protein ligase that mediates ubiquitination of Delta receptors to positively regulate Notch signaling through receptor endocytosis. Mutations cause autosomal recessive developmental delay, intellectual disability, and distinctive facial features. This gene is highly constrained against loss-of-function variants (LOEUF 0.62), suggesting that complete protein loss is likely pathogenic.
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Typical tolerance to LoF variation
Mild missense constraint
The highest-scoring mechanism for this gene is gain-of-function.
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
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
MIB2 · 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 →External Resources
Links to major genomics databases and tools