CBL (E3 ubiquitin-protein ligase CBL) variants and mutations

CBL (also known as E3 ubiquitin-protein ligase CBL) is a human protein-coding gene encoding an e3 ubiquitin-protein ligase protein. It limits receptor-tyrosine-kinase signaling by ubiquitinating activated receptors and promoting their internalization and degradation. Germline or somatic pathogenic variants can prolong RAS-MAPK signaling and cause Noonan-like developmental disease or myeloid malignancy. This analysis covers 2,244 CBL variants and mutations. Of these, 59% have computational variant effect predictions. Disease context includes Noonan syndrome-like disorder with juvenile myelomonocytic leukemia, CBL-related disorder, and juvenile myelomonocytic leukemia. Example CBL variants include M1V, A2P, and A2V.

Variant analysis overview

Variant and mutation evidence

Clinical, disease, and population context

Protein structure and variant hotspots

Data sources

Evidence in this analysis draws on EBI Proteins Variation, UniProt, gnomAD v4, EuropePMC, 3D Hotspot Analysis, Interaction Network Analysis, Protein Data Bank, AlphaFold DB, gnomAD constraint, Open Targets, ClinGen, MaveDB, LitVar.

Notable CBL variants

Examples include M1V, A2P, A2V, A2S, A2T, A2D, A2G, A2A. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.