RHEB

Chr 7q36.1

Ras homolog, mTORC1 binding

MANE:: ENST00000262187.10

OMIM: 601293 ↗NCBI: 6009 ↗Ensembl ↗

Annotations refreshed 9 hours ago.

Predicted protein structure

AlphaFold predicted structure

RHEB · Q15382

v62025-08-01

Predicted Aligned Error matrix for RHEB — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

92.5/ 100

Very high

184 residues

Confidence breakdown

Very high(≥ 90)83%
Confident(70–90)10%
Low(50–70)4%
Very low(< 50)3%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Early onset or syndromic epilepsy
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Intellectual disability
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Fetal anomalies
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Disease associations (Open Targets)

isolated focal cortical dysplasia type II
0.34
neurodegenerative disease
0.29
coronary artery disorder
0.27
hemimegalencephaly
0.27
response to xenobiotic stimulus
0.27
Intellectual disability
0.27
deficiency anemia
0.25
poisoning
0.25
coronary atherosclerosis
0.17
gout
0.13

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

GTP-binding protein Rheb

Small GTPase that acts as an allosteric activator of the canonical mTORC1 complex, an evolutionarily conserved central nutrient sensor that stimulates anabolic reactions and macromolecule biosynthesis to promote cellular biomass generation and growth (PubMed:12172553, PubMed:12271141, PubMed:12842888, PubMed:12869586, PubMed:12906785, PubMed:15340059, PubMed:15854902, PubMed:16098514, PubMed:20381137, PubMed:22819219, PubMed:24529379, PubMed:29416044, PubMed:32470140, PubMed:33157014, PubMed:25816988). In response to nutrients, growth factors or amino acids, specifically activates the protein kinase activity of MTOR, the catalytic component of the mTORC1 complex: acts by causing a conformational change that allows the alignment of residues in the active site of MTOR, thereby enhancing the phosphorylation of ribosomal protein S6 kinase (RPS6KB1 and RPS6KB2) and EIF4EBP1 (4E-BP1) (PubMed:29236692, PubMed:33157014). RHEB is also required for localization of the TSC-TBC complex to lysosomal membranes (PubMed:24529379). In response to starvation, RHEB is inactivated by the TSC-TBC complex, preventing activation of mTORC1 (PubMed:24529379, PubMed:33157014). Has low intrinsic GTPase activity (PubMed:15340059)