RHEB (GTP-binding protein Rheb) variants and mutations

RHEB (also known as GTP-binding protein Rheb) is a human protein-coding gene encoding a GTP-binding protein. Its GTP-bound form directly activates mTORC1 in response to growth and nutrient signals and is normally restrained by the TSC1-TSC2 complex. Activating variants can cause neurodevelopmental overgrowth and epilepsy phenotypes through excessive mTOR signaling. This analysis covers 293 RHEB variants and mutations. Of these, 77% have computational variant effect predictions. Disease context includes isolated focal cortical dysplasia type II, neurodegenerative disease, and coronary artery disorder. Example RHEB variants include S4Y, S6A, and I11M.

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, MaveDB, LitVar.

Notable RHEB variants

Examples include S4Y, S6A, I11M, G13D, G13S, Y14C, R15P, R15Q. Listed records include available protein-change notation, database identifiers, clinical classifications, computational predictions, population evidence, experimental measurements, and disease context.