RPTOR

regulatory associated protein of MTOR complex 1, the group of Armadillo like helical domain containing|WD repeat domain containing|MTOR complex 1

Basic information

Region (hg38): 17:80544818-80966371

Links

ENSG00000141564 ∙ NCBI:57521 ∙ OMIM:607130 ∙ HGNC:30287 ∙ Uniprot:Q8N122 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

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

• Inborn genetic diseases (26 variants)
• not provided (11 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the RPTOR 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				3	6	9
missense			26			26
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				1		1
non coding					1	1
Total	0	0	26	3	7

Variants in RPTOR

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

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

Position	Type	Phenotype	Significance	ClinVar
17-80643745-C-G		not specified	Uncertain significance (Dec 21, 2023)
17-80754019-A-G		not specified	Uncertain significance (Aug 10, 2021)
17-80754115-A-G		not specified	Uncertain significance (Jan 26, 2022)
17-80822218-A-G		not specified	Uncertain significance (Jul 28, 2021)
17-80822229-A-G		not specified	Uncertain significance (Jun 29, 2023)
17-80823169-A-G		not specified	Uncertain significance (Aug 30, 2021)
17-80837969-C-T		not specified	Uncertain significance (Sep 25, 2023)
17-80837970-G-A			Benign (Dec 31, 2019)
17-80846530-G-A		not specified	Uncertain significance (Aug 04, 2021)
17-80857839-C-T		not specified	Uncertain significance (Aug 10, 2021)
17-80857845-G-A		not specified	Uncertain significance (Dec 17, 2023)
17-80880473-C-T		not specified	Uncertain significance (Dec 27, 2022)
17-80883428-C-A			Likely benign (Jul 01, 2023)
17-80883477-C-T		not specified	Uncertain significance (Feb 06, 2024)
17-80883478-G-A			Benign (Jul 11, 2018)
17-80883849-G-T			Likely benign (Apr 24, 2018)
17-80883927-C-T			Benign (Jul 11, 2018)
17-80883970-G-A		not specified	Uncertain significance (Mar 11, 2024)
17-80885016-C-T			Benign (Jul 22, 2018)
17-80885134-C-G		not specified	Uncertain significance (Apr 13, 2022)
17-80885147-A-T		not specified	Uncertain significance (Apr 25, 2023)
17-80891747-G-A		not specified	Uncertain significance (Jan 07, 2022)
17-80891750-G-T		not specified	Uncertain significance (Oct 22, 2021)
17-80893793-C-T		not specified	Likely benign (Feb 13, 2024)
17-80893835-A-G		not specified	Uncertain significance (Dec 19, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
RPTOR	protein_coding	protein_coding	ENST00000306801	34	421553

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	8.31e-11	125742	0	6	125748	0.0000239

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.94	473	887	0.533	0.0000608	8741
Missense in Polyphen		91	301.45	0.30187		2909
Synonymous	-0.175	391	387	1.01	0.0000309	2618
Loss of Function	7.81	3	76.8	0.0390	0.00000406	794

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000638	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000562	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.0000352	0.0000352
Middle Eastern	0.0000562	0.0000544
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in the control of the mammalian target of rapamycin complex 1 (mTORC1) activity which regulates cell growth and survival, and autophagy in response to nutrient and hormonal signals; functions as a scaffold for recruiting mTORC1 substrates. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1- mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Involved in ciliogenesis. {ECO:0000269|PubMed:12150925, ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:23727834}.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Longevity regulating pathway - multiple species - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Autophagy - other - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Thermogenesis - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);AMP-activated Protein Kinase (AMPK) Signaling;Target Of Rapamycin (TOR) Signaling;PI3K-AKT-mTOR signaling pathway and therapeutic opportunities;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Steatosis AOP;Pathways in clear cell renal cell carcinoma;PI3K-Akt Signaling Pathway;Interferon type I signaling pathways;Signal Transduction;Gene expression (Transcription);HSF1-dependent transactivation;Generic Transcription Pathway;Cellular responses to stress;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;Cellular response to heat stress;Transcriptional Regulation by TP53;Intracellular signaling by second messengers;mTOR signaling pathway;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);LKB1 signaling events;insulin (Consensus)

Intolerance Scores

• loftool: 0.0334
• rvis_EVS: -2.58
• rvis_percentile_EVS: 0.83

Haploinsufficiency Scores

• hipred: Y
• hipred_score: 0.825
• ghis: 0.562

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.860

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Rptor
• Phenotype: embryo phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system 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); reproductive system phenotype; hematopoietic system phenotype; digestive/alimentary phenotype; immune system phenotype; skeleton phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype

Gene ontology

• Biological process: regulation of cell growth;positive regulation of endothelial cell proliferation;cell cycle arrest;regulation of cell size;cellular response to starvation;positive regulation of peptidyl-threonine phosphorylation;viral process;regulation of macroautophagy;positive regulation of cell growth;cellular response to nutrient levels;TOR signaling;positive regulation of TOR signaling;activation of protein kinase activity;positive regulation of peptidyl-serine phosphorylation;TORC1 signaling;positive regulation of transcription by RNA polymerase III;cellular response to amino acid stimulus;cellular response to leucine;negative regulation of protein serine/threonine kinase activity;positive regulation of protein serine/threonine kinase activity;regulation of cellular response to heat;positive regulation of G1/S transition of mitotic cell cycle
• Cellular component: nucleoplasm;cytoplasm;lysosome;lysosomal membrane;cytosol;cytoplasmic stress granule;dendrite;TORC1 complex;neuronal cell body
• Molecular function: RNA polymerase III type 1 promoter DNA binding;RNA polymerase III type 2 promoter DNA binding;RNA polymerase III type 3 promoter DNA binding;TFIIIC-class transcription factor complex binding;protein binding;protein kinase binding;protein serine/threonine kinase inhibitor activity;protein kinase activator activity;protein binding, bridging;protein-containing complex binding;14-3-3 protein binding