RHEB

Ras homolog, mTORC1 binding, the group of RAS type GTPase family

Basic information

Region (hg38): 7:151466011-151520120

Previous symbols: [ "RHEB2" ]

Links

ENSG00000106615 ∙ NCBI:6009 ∙ OMIM:601293 ∙ HGNC:10011 ∙ Uniprot:Q15382 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• complex neurodevelopmental disorder (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the RHEB gene.

• not provided (7 variants)
• Malignant neoplasm of body of uterus (1 variants)
• Transitional cell carcinoma of the bladder (1 variants)
• Papillary renal cell carcinoma type 1 (1 variants)
• Hemimegalencephaly (1 variants)
• Neurodevelopmental delay;Seizure (1 variants)
• Papillary renal cell carcinoma, sporadic (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RHEB gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous						0
missense	2	1	4			7
nonsense						0
start loss						0
frameshift			1			1
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region					1	1
non coding						0
Total	2	1	5	0	0

Variants in RHEB

This is a list of pathogenic ClinVar variants found in the RHEB region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-151467187-T-C			Uncertain significance (Jan 19, 2023)
7-151470624-A-C			Uncertain significance (Feb 15, 2023)
7-151470644-C-G		not specified	Uncertain significance (Mar 08, 2024)
7-151471448-G-A		RHEB-related disorder	Benign (May 12, 2021)
7-151490948-T-A		Hemimegalencephaly	Likely pathogenic (-)
7-151490963-T-C		Papillary renal cell carcinoma type 1 • Malignant neoplasm of body of uterus • Papillary renal cell carcinoma, sporadic • Transitional cell carcinoma of the bladder	Pathogenic (Mar 30, 2021)
7-151490963-T-G			Pathogenic (Aug 18, 2022)
7-151490964-A-T		Malignant neoplasm of body of uterus • Papillary renal cell carcinoma type 1 • Papillary renal cell carcinoma, sporadic • Transitional cell carcinoma of the bladder	Likely pathogenic (May 31, 2016)
7-151490996-A-G			Uncertain significance (Aug 02, 2023)
7-151519460-CCA-C			Uncertain significance (Jul 19, 2022)
7-151519465-G-A		Seizure;Neurodevelopmental delay	Uncertain significance (Sep 30, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RHEB	protein_coding	protein_coding	ENST00000262187	8	54109

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.981	0.0188	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.30	33	96.6	0.342	0.00000458	1205
Missense in Polyphen		2	38.917	0.051392		508
Synonymous	0.127	35	36.0	0.973	0.00000199	337
Loss of Function	3.23	0	12.1	0.00	5.79e-7	150

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Activates the protein kinase activity of mTORC1, and thereby plays a role in the regulation of apoptosis. Stimulates the phosphorylation of S6K1 and EIF4EBP1 through activation of mTORC1 signaling. Has low intrinsic GTPase activity. {ECO:0000269|PubMed:12271141, ECO:0000269|PubMed:12869586, ECO:0000269|PubMed:15340059, ECO:0000269|PubMed:15854902, ECO:0000269|PubMed:16098514, ECO:0000269|PubMed:20381137}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Choline metabolism in cancer - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Thyroid hormone signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Cellular senescence - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Leucine Stimulation on Insulin Signaling;Target Of Rapamycin (TOR) Signaling;miR-targeted genes in epithelium - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;miR-targeted genes in squamous cell - TarBase;Follicle Stimulating Hormone (FSH) signaling pathway;Polycystic Kidney Disease Pathway;BDNF-TrkB Signaling;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Pathways in clear cell renal cell carcinoma;PI3K-Akt Signaling Pathway;Insulin Signaling;Signal Transduction;Gene expression (Transcription);mtor signaling pathway;Generic Transcription Pathway;RNA Polymerase II Transcription;mTORC1-mediated signalling;Energy dependent regulation of mTOR by LKB1-AMPK;mTOR signalling;insulin Mam;TP53 Regulates Metabolic Genes;Macroautophagy;Cellular responses to external stimuli;Regulation of PTEN gene transcription;PTEN Regulation;PIP3 activates AKT signaling;Transcriptional Regulation by TP53;Intracellular signaling by second messengers;mTOR signaling pathway;insulin (Consensus)

Recessive Scores

• pRec: 0.171

Intolerance Scores

• rvis_EVS: 0.01
• rvis_percentile_EVS: 54.63

Haploinsufficiency Scores

• pHI: 0.783
• hipred: Y
• hipred_score: 0.729
• ghis: 0.681

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.942

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Low	Medium
Primary Immunodeficiency	Medium	Low	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Rheb
• Phenotype: homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype; growth/size/body region phenotype; embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Gene ontology

• Biological process: cell cycle arrest;signal transduction;regulation of macroautophagy;positive regulation of TOR signaling;positive regulation of oligodendrocyte differentiation;negative regulation of cold-induced thermogenesis;regulation of type B pancreatic cell development
• Cellular component: Golgi membrane;spliceosomal complex;lysosomal membrane;endoplasmic reticulum membrane;cytosol;postsynaptic density;membrane;extracellular exosome
• Molecular function: magnesium ion binding;GTPase activity;protein binding;GTP binding;GDP binding;protein kinase binding