CUL3 (Cullin-3) variants and mutations

CUL3 (also known as Cullin-3) is a human protein-coding gene encoding a cullin-3 protein. It serves as a scaffold for multiple ubiquitin-ligase complexes that control degradation of signaling and regulatory proteins, including components of the KEAP1-NRF2 pathway. Pathogenic variants can cause pseudohypoaldosteronism type II and neurodevelopmental disorders, while somatic alterations affect cancer signaling. This analysis covers 2,587 CUL3 variants and mutations. Of these, 27% have computational variant effect predictions. Disease context includes neurodevelopmental disorder with or without autism or seizures, pseudohypoaldosteronism type 2E, and neurodegenerative disease. Example CUL3 variants include S2*, S2W, and S2C.

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 CUL3 variants

Examples include S2*, S2W, S2C, N3S, S5I, S5N, S5R, K6N. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.