RICTOR

Summary

RICTOR (RPTOR independent companion of MTOR complex 2, HGNC:28611) is a protein-coding gene on chromosome 5p13.1, encoding Rapamycin-insensitive companion of mTOR (Q6R327). Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output. In precision oncology, RICTOR Amplification confers sensitivity to Sapanisertib + Onatasertib in Lung Adenocarcinoma (CIViC Level C); 3 further curated variant–drug associations are listed below. It is a selective cancer dependency (DepMap: 39.2% of cell lines).

RICTOR and MTOR (FRAP1; MIM 601231) are components of a protein complex that integrates nutrient- and growth factor-derived signals to regulate cell growth (Sarbassov et al., 2004 [PubMed 15268862]).

Source: NCBI Gene 253260 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 6
• Clinical variants (ClinVar): 171 total — 2 likely-pathogenic
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 4 curated variant–drug associations
• Cancer dependency (DepMap): dependent in 39.2% of screened cell lines
• MANE Select transcript: NM_152756

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28611
Approved symbol	RICTOR
Name	RPTOR independent companion of MTOR complex 2
Location	5p13.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC39830, AVO3, PIA, KIAA1999
Ensembl gene	ENSG00000164327
Ensembl biotype	protein_coding
OMIM	609022
Entrez	253260

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 6 protein_coding, 4 retained_intron, 1 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000296782, ENST00000357387, ENST00000503698, ENST00000505927, ENST00000509567, ENST00000510711, ENST00000511516, ENST00000513566, ENST00000514735, ENST00000515846, ENST00000711063, ENST00000857125

RefSeq mRNA: 3 — MANE Select: NM_152756 NM_001285439, NM_001285440, NM_152756

CCDS: CCDS34148, CCDS68861

Canonical transcript exons

ENST00000357387 — 38 exons

Exon	Start	End
ENSE00001212788	38945491	38945724
ENSE00002052088	38937920	38942378
ENSE00003464519	38962876	38963041
ENSE00003478344	38971877	38971959
ENSE00003484136	38960398	38960533
ENSE00003503695	38975537	38975604
ENSE00003503710	38953461	38953553
ENSE00003510920	38967337	38967427
ENSE00003512663	38952985	38953091
ENSE00003514402	38942833	38942971
ENSE00003525009	38958443	38958519
ENSE00003527552	38952196	38952425
ENSE00003529956	38957652	38957730
ENSE00003533048	38962315	38962361
ENSE00003533404	38949712	38950720
ENSE00003542107	38978583	38978650
ENSE00003542944	39002535	39002666
ENSE00003552976	38947264	38947441
ENSE00003561502	38959779	38959978
ENSE00003567429	38958667	38958831
ENSE00003568493	38967161	38967227
ENSE00003582795	38954774	38954861
ENSE00003597247	39021039	39021136
ENSE00003599211	38981867	38982036
ENSE00003608771	38990949	38991075
ENSE00003609307	38967943	38968030
ENSE00003615900	39074329	39074399
ENSE00003628293	39003558	39003622
ENSE00003634715	38944913	38945068
ENSE00003635841	38966641	38966721
ENSE00003636347	39074111	39074158
ENSE00003647187	38955595	38955704
ENSE00003650482	38959195	38959321
ENSE00003650674	38944446	38944569
ENSE00003677035	38964792	38964892
ENSE00003679331	38962485	38962586
ENSE00003688690	38946468	38946552
ENSE00003692105	38996819	38996882

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 98.34.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.9552 / max 810.2792, expressed in 1804 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
61366	28.4923	1802
61361	0.2406	92
61365	0.2222	65

Top tissues by expression

263 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	98.34	gold quality
corpus callosum	UBERON:0002336	97.53	gold quality
tibialis anterior	UBERON:0001385	97.52	gold quality
mucosa of paranasal sinus	UBERON:0005030	97.04	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.94	gold quality
superficial temporal artery	UBERON:0001614	96.67	gold quality
left ventricle myocardium	UBERON:0006566	96.51	gold quality
Brodmann (1909) area 23	UBERON:0013554	96.32	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	96.29	gold quality
deltoid	UBERON:0001476	96.12	gold quality
cauda epididymis	UBERON:0004360	96.04	gold quality
caput epididymis	UBERON:0004358	95.99	gold quality
myocardium	UBERON:0002349	95.97	gold quality
lower lobe of lung	UBERON:0008949	95.81	gold quality
inferior vagus X ganglion	UBERON:0005363	95.72	gold quality
nipple	UBERON:0002030	95.53	gold quality
upper arm skin	UBERON:0004263	95.34	gold quality
subthalamic nucleus	UBERON:0001906	95.23	gold quality
germinal epithelium of ovary	UBERON:0001304	95.16	gold quality
ileal mucosa	UBERON:0000331	95.04	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.97	gold quality
epithelial cell of pancreas	CL:0000083	94.82	gold quality
medulla oblongata	UBERON:0001896	94.82	gold quality
corpus epididymis	UBERON:0004359	94.78	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	94.75	gold quality
saphenous vein	UBERON:0007318	94.72	gold quality
medial globus pallidus	UBERON:0002477	94.70	gold quality
mammary duct	UBERON:0001765	94.66	gold quality
epithelium of mammary gland	UBERON:0003244	94.60	gold quality
calcaneal tendon	UBERON:0003701	94.59	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-8142	yes	16.80
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB

miRNA regulators (miRDB)

363 targeting RICTOR, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-4803	99.98	71.99	3117

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 39.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• results show show that target of rapamycin (TOR) kinase and its associated protein rictor are necessary for AKT/PKB Ser473 phosphorylation and that a reduction in rictor or mammalian TOR (mTOR) expression inhibited an Akt/PKB effector (PMID:15718470)
• These data suggest that, during HCMV infection, the rictor- and raptor-containing complexes are modified such that their substrate specificities and rapamycin sensitivities are altered. (PMID:16959881)
• Results reveal that the SIN1-rictor-mTOR function in Akt-Ser473 phosphorylation is required for TORC2 function in cell survival but is dispensable for TORC1 function. (PMID:16962653)
• Sin1 together with Rictor are key components of mTORC2 and play an essential role in Akt phosphorylation and signaling (PMID:17043309)
• ASCT2 silencing inhibits mTORC1 (mTOR/raptor) signaling and leads to growth repression, followed by enhanced survival signaling via mTORC2 (mTOR/rictor) and apoptosis of hepatoma cells. (PMID:17329400)
• It was demonstrated that immunoprecipitation of Protor-1 or Protor-2 results in the co-immunoprecipitation of other mTORC2 subunits, but not Raptor, a specific component of mTORC1. (PMID:17461779)
• mTORC2 is hyperactivated in gliomas and promotes tumor cell proliferation and invasive potential due to increased complex formation as a result of the overexpression of rictor. (PMID:18089801)
• Hsp70 was isolated as a putative Rictor interacting protein. (PMID:18505677)
• there are two parallel cell-survival pathways in prostate cancer cells: a strong Akt-independent, but rapamycin-sensitive pathway downstream of mTORC1, and an AR-dependent pathway downstream of mTORC2 and Akt, that is stimulated by mTORC1 inhibition (PMID:18776922)
• TORC2 inhibition reduced proliferation and anchorage-independent growth of breast cancer and prostate cancer cell lines. (PMID:18831768)
• mTORC2 and Akt facilitate CD40-inducible expression of VEGF in endothelial cells (PMID:19018001)
• S2448 phosphorylated mTOR binds to both raptor and rictor. (PMID:19145465)
• mTORC1 and mTORC2 complexes have distinct, non-redundant functions in MO7e MK cell proliferation, and development (PMID:19341427)
• This study describes the small molecule Ku-0063794, which inhibits both mTORC1 and mTORC2, but does not suppress the activity of 76 other protein kinases or seven lipid kinases. (PMID:19402821)
• Report involvement of mTORC1 and mTORC2 in regulation of glioblastoma multiforme growth and motility. (PMID:19724909)
• inhibition of the mTORC2 protein Rictor leads to growth inhibition and induces apoptosis in both rapamycin-sensitive and rapamycin-resistant colorectal cancers (PMID:19934294)
• found that Rictor phosphorylation requires mTOR complex 1 activity and, more specifically, the p70 ribosomal S6 kinase 1 (S6K1). (PMID:19995915)
• The inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo. (PMID:20226010)
• SGK1 interacted selectively with rictor but not with raptor, suggesting selective recruitment of SGK1 to mTORC2. (PMID:20338997)
• FoxOs inhibit mTORC1 and activate Akt by inducing the expression of Sestrin3 and Rictor (PMID:20412774)
• This study reveals that mTORC2 is a critical target of PLD-mediated survival signals and identifies SGK1 as a downstream target of mTORC2 for the stabilization of HDM2. (PMID:20438709)
• Rictor phosphorylation takes place in mammalian target of rapamycin (mTORC)2-deficient cells; this modification may play a role in regulating not only mTORC2 but also the mTORC2-independent function of rictor. (PMID:20501647)
• Rictor forms a complex with Cullin-1 to promote SGK1 ubiquitination and destruction. (PMID:20832730)
• Fndings identify Rictor as an important mediator of chemotaxis and metastasis in breast cancer cells. (PMID:20978191)
• There is an increased mitochondrial dependence upon mTORC2 dependent cell growth due to PTEN loss (PMID:21170086)
• PINK1 exerts its cytoprotective function not only in mitochondria but also in the cytoplasm through activation of mTORC2 (PMID:21177249)
• in response to cellular stress, GSK-3beta restrains mTORC2-Akt signaling by specifically phosphorylating rictor, thereby balancing the activities of GSK-3beta and Akt, two opposing players in glucose metabolism (PMID:21343617)
• Rictor is a novel target of miR-218, suggesting that activation of the mTOR-Akt signaling pathway induced by Rictor contributes centrally to oral carcinogenesis. (PMID:21795477)
• RICTOR overexpression in sarcomas and its links to therapeutic response need to be assessed (PMID:22080063)
• multiple-site acetylation of Rictor signals for increased activation of mTORC2, providing a critical link between nutrient-sensitive deacetylases and mTORC2 signaling to Akt (PMID:22084251)
• these results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells. (PMID:22285861)
• analysis of the role of RICTOR in beta1 integrin-mediated cell survival and how receptor-specific mechanisms regulate phosphorylation of AKT at Ser473 (PMID:22384145)
• Rictor by suppressing RhoGDI2 promotes activity of the Rho proteins and cell migration. (PMID:22777355)
• High rictor expression is associated with hemangioendothelioma. (PMID:23067215)
• Reduced mTORC2 activity impairs both long-term memory and the late phase of hippocampal long-term potentiation. (PMID:23455608)
• The expression of Raptor was associated with a higher tumour grade. (PMID:23503572)
• combined silencing of EGFR and Rictor should be an effective means of treating glioblastoma (PMID:23555046)
• NBS1 interacts with the mTOR/Rictor/SIN1 complex through the a.a. 221-402 domain and contributes to the activation of Akt activity. (PMID:23762398)
• IKK interacts with rictor and regulates the function of mTORC2 including phosphorylation of AKT (at Serine473) and organization of actin cytoskeleton. (PMID:23872070)
• Histolopathological and clinical information including tumour stage, invasion characteristic and endocrine status were analysed against the gene transcript expression of mTOR, RAPTOR and RICTOR. (PMID:23898069)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	rictorb	ENSDARG00000002020
danio_rerio	rictora	ENSDARG00000100867
mus_musculus	Rictor	ENSMUSG00000050310
rattus_norvegicus	Rictor	ENSRNOG00000011341
drosophila_melanogaster	rictor	FBGN0031006
caenorhabditis_elegans		WBGENE00009245

Protein

Protein identifiers

Rapamycin-insensitive companion of mTOR — Q6R327 (reviewed: Q6R327)

Alternative names: AVO3 homolog

All UniProt accessions (4): A0AA34QVL6, A0AA34QVX7, D6R9S6, Q6R327

UniProt curated annotations — full annotation on UniProt →

Function. Component of the mechanistic target of rapamycin complex 2 (mTORC2), which transduces signals from growth factors to pathways involved in proliferation, cytoskeletal organization, lipogenesis and anabolic output. In response to growth factors, mTORC2 phosphorylates and activates AGC protein kinase family members, including AKT (AKT1, AKT2 and AKT3), PKC (PRKCA, PRKCB and PRKCE) and SGK1. In contrast to mTORC1, mTORC2 is nutrient-insensitive. Within the mTORC2 complex, RICTOR probably acts as a molecular adapter. RICTOR is responsible for the FKBP12-rapamycin-insensitivity of mTORC2. mTORC2 plays a critical role in AKT1 activation by mediating phosphorylation of different sites depending on the context, such as ‘Thr-450’, ‘Ser-473’, ‘Ser-477’ or ‘Thr-479’, facilitating the phosphorylation of the activation loop of AKT1 on ‘Thr-308’ by PDPK1/PDK1 which is a prerequisite for full activation. mTORC2 catalyzes the phosphorylation of SGK1 at ‘Ser-422’ and of PRKCA on ‘Ser-657’. The mTORC2 complex also phosphorylates various proteins involved in insulin signaling, such as FBXW8 and IGF2BP1. mTORC2 acts upstream of Rho GTPases to regulate the actin cytoskeleton, probably by activating one or more Rho-type guanine nucleotide exchange factors. mTORC2 promotes the serum-induced formation of stress-fibers or F-actin.

Subunit / interactions. Component of the mechanistic target of rapamycin complex 2 (mTORC2), consisting in two heterotretramers composed of MTOR, MLST8, RICTOR and MAPKAP1/SIN1. The mTORC2 core complex associates with PRR5/PROTOR1 and/or PRR5L/PROTOR2. Contrary to mTORC1, mTORC2 does not bind to and is not sensitive to FKBP12-rapamycin. Binds directly to MTOR and PRR5 within the TORC2 complex; interaction with MTOR is enhanced by deubiquitination of RICTOR by USP9X. Interaction with MAPKAP1 is not enhanced by RICTOR deubiquitination by USP9X. Interacts with CCDC28B. Interacts with NBN. Interacts with SIK3. Interacts with NCKAP1L. Interacts with kinases GSK3A and GSK3B; the interactions lead to phosphorylation of RICTOR at Thr-1695 which facilitates its FBXW7-mediated ubiquitination and subsequent degradation. Interacts with FBXW7; the interaction is enhanced by GSK3-mediated phosphorylation of Thr-1695 and results in RICTOR ubiquitination and degradation. Interacts with ARMH4 (via cytoplasmic tail); this interaction bridges ARMH4 to the mTORC2 complex and inhibits the mTORC2 kinase activity. Interacts with UBXN2A. Interacts with TSPAN8. (Microbial infection) Interacts with vaccinia virus protein F17; this interaction dysregulates MTOR.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Lysosome membrane.

Post-translational modifications. Phosphorylated by MTOR; when part of mTORC2. Phosphorylated at Thr-1135 by RPS6KB1 downstream of the mTORC1 complex: phosphorylation of RICTOR inhibits mTORC2 signaling by creating a binding site for 14-3-3 proteins. Phosphorylated at Thr-1695 by GSK3A and GSK3B which facilitates RICTOR ubiquitination and subsequent degradation. Phosphorylated at Ser-1235 by GSK3B in response to endoplasmic stress, inhibiting mTORC2 signaling. Ubiquitinated by the SCF(FBXW7) complex, leading to its degradation by the proteasome. Deubiquitinated by USP9X; deubiquitination stabilizes RICTOR and enhances its binding to MTOR, thus promoting mTORC2 complex assembly. Acetylated by EP300/p300 in response to glucose, leading to activate the mTORC2 complex. Acetylation by BLOC1S1/GCN5L1 in response to hypotoxic stress protects RICTOR against ubiquitination and subsequent degradation by the proteasome.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the RICTOR family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q6R327-1	1	yes
Q6R327-4	2
Q6R327-3	3

RefSeq proteins (3): NP_001272368, NP_001272369, NP_689969* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR016024	ARM-type_fold	Homologous_superfamily
IPR028267	Pianissimo_N	Domain
IPR028268	Pianissimo_fam	Family
IPR029259	RICTOR_phospho	PTM
IPR029451	RICTOR_M	Domain
IPR029452	RICTOR_V	Domain
IPR029453	Rictor_IV	Domain

Pfam: PF14663, PF14664, PF14665, PF14666, PF14668

UniProt features (176 total): helix 73, modified residue 36, strand 18, turn 14, mutagenesis site 9, binding site 7, region of interest 6, sequence conflict 4, splice variant 3, compositionally biased region 3, chain 1, cross-link 1, sequence variant 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
9T94	ELECTRON MICROSCOPY	2.6
9ZBK	ELECTRON MICROSCOPY	2.6
9T93	ELECTRON MICROSCOPY	2.86
6ZWO	ELECTRON MICROSCOPY	3
9T7J	ELECTRON MICROSCOPY	3
9TDT	ELECTRON MICROSCOPY	3
9T92	ELECTRON MICROSCOPY	3.1
6ZWM	ELECTRON MICROSCOPY	3.2
7PE8	ELECTRON MICROSCOPY	3.2
9ZBJ	ELECTRON MICROSCOPY	3.2
7TZO	ELECTRON MICROSCOPY	3.28
9TDS	ELECTRON MICROSCOPY	3.3
7PE7	ELECTRON MICROSCOPY	3.41
7PE9	ELECTRON MICROSCOPY	3.7
5ZCS	ELECTRON MICROSCOPY	4.9
9TPW	ELECTRON MICROSCOPY	6.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6R327-F1	66.57	0.26

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (7): 543; 572; 576; 1515; 1520; 1523; 1651

Post-translational modifications (37): 21, 35, 265, 1092, 1095, 1103, 1116, 1119, 1125, 1135, 1138, 1162, 1219, 1235, 1271, 1274, 1278, 1282, 1284, 1295 …

Mutagenesis-validated functional residues (9):

Position	Phenotype
274	abolishes deubiquitination by usp9x and increases interaction with mtor. no effect on interaction with sin1.
1080–1082	in m1; does not affect acetylation.
1092–1095	in m2; decreased acetylation and activity of the mtorc2 complex.
1107–1108	in m3; does not affect acetylation.
1116–1125	in m4; decreased acetylation and activity of the mtorc2 complex.
1135	impaired phosphorylation by rps6kb1, leading to increased activity of the mtorc2 complex.
1235	impaired phosphorylation by gsk3b in response to stress, leading to increased mtorc2 activity.
1235	mimics phosphorylation; decreased activity of mtorc2.
1695	reduced gsk3-mediated phosphorylation, reduced interaction with fbxw7, reduced fbxw7-mediated ubiquitination and increas

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-5218920	VEGFR2 mediated vascular permeability
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-6804757	Regulation of TP53 Degradation
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9920951	Dengue virus modulates apoptosis

MSigDB gene sets: 431 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, ACTACCT_MIR196A_MIR196B, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, TGCACTT_MIR519C_MIR519B_MIR519A, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_GROWTH, ATGCAGT_MIR217, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS

GO Biological Process (22): positive regulation of endothelial cell proliferation (GO:0001938), cytoskeleton organization (GO:0007010), lipid biosynthetic process (GO:0008610), embryo development ending in birth or egg hatching (GO:0009792), regulation of gene expression (GO:0010468), actin cytoskeleton organization (GO:0030036), positive regulation of cell growth (GO:0030307), positive regulation of cell migration (GO:0030335), positive regulation of actin filament polymerization (GO:0030838), cellular response to nutrient levels (GO:0031669), positive regulation of TOR signaling (GO:0032008), regulation of actin cytoskeleton organization (GO:0032956), TORC2 signaling (GO:0038203), negative regulation of apoptotic process (GO:0043066), regulation of inflammatory response (GO:0050727), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), regulation of establishment of cell polarity (GO:2000114), TOR signaling (GO:0031929), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), cGAS/STING signaling pathway (GO:0140896), negative regulation of cGAS/STING signaling pathway (GO:0160049)

GO Molecular Function (9): ATP binding (GO:0005524), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), ribosome binding (GO:0043022), protein serine/threonine kinase activator activity (GO:0043539), molecular adaptor activity (GO:0060090), enzyme-substrate adaptor activity (GO:0140767), nucleotide binding (GO:0000166), protein binding (GO:0005515)

GO Cellular Component (10): lysosome (GO:0005764), lysosomal membrane (GO:0005765), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), TORC2 complex (GO:0031932), membrane (GO:0016020), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Intracellular signaling by second messengers	1
Co-stimulation by CD28	1
VEGFA-VEGFR2 Pathway	1
PI3K/AKT Signaling in Cancer	1
Regulation of TP53 Expression and Degradation	1
Response of endothelial cells to shear stress	1
Dengue Virus-Host Interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	3
TOR signaling	2
positive regulation of intracellular signal transduction	2
phosphatidylinositol 3-kinase/protein kinase B signal transduction	2
binding	2
endomembrane system	2
intracellular membrane-bounded organelle	2
cellular anatomical structure	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
organelle organization	1
lipid metabolic process	1
biosynthetic process	1
embryo development	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cytoskeleton organization	1
actin filament-based process	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
actin filament polymerization	1
regulation of actin filament polymerization	1
positive regulation of protein polymerization	1
positive regulation of cytoskeleton organization	1
positive regulation of supramolecular fiber organization	1
response to nutrient levels	1
cellular response to stimulus	1
regulation of TOR signaling	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1

Protein interactions and networks

STRING

2702 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RICTOR	MAPKAP1	Q9BPZ7	999
RICTOR	MTOR	P42345	999
RICTOR	PRR5	P85299	999
RICTOR	RPTOR	Q8N122	999
RICTOR	MLST8	Q9BVC4	999
RICTOR	PRR5L	Q6MZQ0	998
RICTOR	DEPTOR	Q8TB45	997
RICTOR	TTI1	O43156	996
RICTOR	AKT1S1	Q96B36	994
RICTOR	ILK	P57043	968
RICTOR	FKBP1A	P20071	921
RICTOR	RPS6KB1	P23443	903
RICTOR	TSC2	P49815	901
RICTOR	CUL1	Q13616	901
RICTOR	HSPA4	P34932	893

IntAct

264 interactions, top by confidence:

A	B	Type	Score
RPTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.980
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
RICTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.970
MTOR	RICTOR	psi-mi:“MI:0915”(physical association)	0.970
MTOR	RICTOR	psi-mi:“MI:0914”(association)	0.970
ILK	LIMS1	psi-mi:“MI:0914”(association)	0.960
MAPKAP1	MTOR	psi-mi:“MI:0914”(association)	0.860
TUBGCP5	TUBG1	psi-mi:“MI:0914”(association)	0.840
RACK1	RPL7	psi-mi:“MI:0403”(colocalization)	0.730
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
ILK	RICTOR	psi-mi:“MI:0915”(physical association)	0.660
RICTOR	ILK	psi-mi:“MI:0915”(physical association)	0.660

BioGRID (1089): RICTOR (Affinity Capture-Western), MTOR (Affinity Capture-Western), PRR5L (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), RICTOR (Affinity Capture-Western), RICTOR (Affinity Capture-MS), RICTOR (Affinity Capture-Western), ILK (Affinity Capture-Western), MTOR (Affinity Capture-Western), RICTOR (Affinity Capture-Western), RICTOR (Two-hybrid), MTOR (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), RICTOR (Affinity Capture-Western), RICTOR (Affinity Capture-Western)

ESM2 similar proteins: A0A3L7I2I8, A0JMZ3, A5HK05, A7MB89, A7YWD2, O60733, O75031, O94829, O94955, P0C7A6, P42694, P49754, P97570, P97819, Q05AL1, Q1LVW0, Q29RM5, Q2KI54, Q2T9K6, Q3UFS0, Q3UJZ3, Q4V890, Q5KU39, Q5R6S3, Q5R974, Q5T9G4, Q5TYQ1, Q5VZK9, Q68FK4, Q6DFV5, Q6EDY6, Q6NYU2, Q6QI06, Q6R327, Q7T3P8, Q8C0T1, Q8CEF1, Q8IUR7, Q8NFZ0, Q91W86

Diamond homologs: O77203, Q6QI06, Q6R327

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
RPS6KB1	down-regulates	RICTOR	phosphorylation
RICTOR	“form complex”	mTORC2	binding
GSK3B	“down-regulates quantity by destabilization”	RICTOR	phosphorylation
GSK3A	“down-regulates quantity by destabilization”	RICTOR	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 187 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Activation of BAD and translocation to mitochondria	7	48.5×	1e-08
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	42.8×	2e-08
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	42.8×	2e-08
Activation of BH3-only proteins	7	31.6×	1e-07
Intrinsic Pathway for Apoptosis	8	21.3×	3e-07
RHO GTPases activate PKNs	7	20.2×	2e-06
HSF1-dependent transactivation	6	17.3×	4e-05
FOXO-mediated transcription	5	15.3×	4e-04

GO biological processes:

GO term	Partners	Fold	FDR
cellular response to nutrient levels	5	14.6×	9e-03
cytoplasmic translation	7	8.1×	9e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

171 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	116
Likely benign	8
Benign	2

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
521034	NM_152756.5(RICTOR):c.4346del (p.Asn1449fs)	Likely pathogenic
929749	NM_152756.5(RICTOR):c.1325A>G (p.His442Arg)	Likely pathogenic

SpliceAI

5448 predictions. Top by Δscore:

Variant	Effect	Δscore
5:38942831:A:AC	donor_gain	1.0000
5:38942832:C:CT	donor_gain	1.0000
5:38942832:CT:C	donor_gain	1.0000
5:38942832:CTT:C	donor_gain	1.0000
5:38942970:TT:T	acceptor_gain	1.0000
5:38942972:C:CC	acceptor_gain	1.0000
5:38944444:A:AC	donor_gain	1.0000
5:38944445:C:CC	donor_gain	1.0000
5:38944505:T:C	donor_gain	1.0000
5:38944515:T:TA	donor_gain	1.0000
5:38944567:CAC:C	acceptor_gain	1.0000
5:38944568:ACC:A	acceptor_loss	1.0000
5:38944908:CTCA:C	donor_loss	1.0000
5:38944909:TCA:T	donor_loss	1.0000
5:38944910:CACCT:C	donor_loss	1.0000
5:38944911:A:AC	donor_gain	1.0000
5:38944911:ACCT:A	donor_loss	1.0000
5:38944912:C:CC	donor_gain	1.0000
5:38944912:CCT:C	donor_gain	1.0000
5:38944912:CCTA:C	donor_gain	1.0000
5:38945065:AAGT:A	acceptor_gain	1.0000
5:38945065:AAGTC:A	acceptor_gain	1.0000
5:38945066:AGT:A	acceptor_gain	1.0000
5:38945066:AGTCT:A	acceptor_gain	1.0000
5:38945067:GT:G	acceptor_gain	1.0000
5:38945067:GTCTG:G	acceptor_gain	1.0000
5:38945068:TCTGA:T	acceptor_gain	1.0000
5:38945069:C:CA	acceptor_loss	1.0000
5:38945069:C:CC	acceptor_gain	1.0000
5:38945069:CTG:C	acceptor_gain	1.0000

AlphaMissense

11256 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:38944452:A:G	L1636P	1.000
5:38953067:C:G	G939R	1.000
5:38953469:A:G	W928R	1.000
5:38953469:A:T	W928R	1.000
5:38954814:A:G	L886P	1.000
5:38957660:A:G	W831R	1.000
5:38957660:A:T	W831R	1.000
5:38957710:C:T	G814E	1.000
5:38957711:C:G	G814R	1.000
5:38957711:C:T	G814R	1.000
5:38958503:A:G	L787P	1.000
5:38958512:A:G	L784P	1.000
5:38958681:C:G	A777P	1.000
5:38958689:A:G	L774P	1.000
5:38958734:A:G	L759P	1.000
5:38958759:C:G	G751R	1.000
5:38958759:C:T	G751R	1.000
5:38958760:C:A	W750C	1.000
5:38958760:C:G	W750C	1.000
5:38958762:A:G	W750R	1.000
5:38958762:A:T	W750R	1.000
5:38959223:A:G	L717P	1.000
5:38960435:C:T	G605D	1.000
5:38962511:A:G	W548R	1.000
5:38962511:A:T	W548R	1.000
5:38962515:C:A	W546C	1.000
5:38962515:C:G	W546C	1.000
5:38962517:A:G	W546R	1.000
5:38962517:A:T	W546R	1.000
5:38975543:A:G	W295R	1.000

dbSNP variants (sampled 300 via entrez): RS1000034056 (5:38955318 A>G), RS1000086489 (5:39000942 A>C,T), RS1000097359 (5:39007619 C>A), RS1000140204 (5:39053123 C>T), RS1000169585 (5:39040373 C>G,T), RS1000177386 (5:39024674 CCAAA>C), RS1000181551 (5:38995684 A>G), RS1000209029 (5:39051833 T>C), RS1000245642 (5:38995398 T>C), RS1000248279 (5:39040374 G>A), RS1000256342 (5:38951681 T>A,G), RS1000261585 (5:39052898 C>T), RS1000302326 (5:38994361 G>A), RS1000368219 (5:39068588 GAAC>G), RS1000394602 (5:39031844 A>G)

Disease associations

OMIM: gene MIM:609022 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (3): primary ovarian failure (MONDO:0005387), Tourette syndrome (MONDO:0007661), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001762_699	Obesity-related traits	8.000000e-07
GCST001762_936	Obesity-related traits	2.000000e-06
GCST003262_232	Post bronchodilator FEV1	3.000000e-06
GCST003518_45	Daytime sleep phenotypes	3.000000e-06
GCST90002387_104	Immature fraction of reticulocytes	3.000000e-16
GCST90002403_396	Red blood cell count	8.000000e-15

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0004314	forced expiratory volume
EFO:0007828	daytime rest measurement
EFO:0004305	erythrocyte count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL1795179 (SINGLE PROTEIN), CHEMBL4523999 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 13,342 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1236962	OMIPALISIB	2	3,989
CHEMBL3120215	OSI-027	2	1,854
CHEMBL3545097	SAPANISERTIB	2	2,524
CHEMBL4084907	BIMIRALISIB	2	1,625
CHEMBL1801204	AZD-8055	1	3,350

Clinical evidence (CIViC)

Drug × variant × indication: 4 predictive associations from 4 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
RICTOR Amplification	Sapanisertib + Onatasertib	Lung Adenocarcinoma	Sensitivity/Response	CIViC C	EID1440
RICTOR Amplification	Vistusertib	Lung Small Cell Carcinoma	Sensitivity/Response	CIViC C	EID7449
RICTOR Amplification	Vistusertib	Gastric Adenocarcinoma	Sensitivity/Response	CIViC D	EID1915
RICTOR Amplification	Vistusertib + MTOR Kinase Inhibitor AZD8055 + Sapanisertib	Lung Small Cell Carcinoma	Sensitivity/Response	CIViC D	EID1916

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs6878291	RICTOR		0.00	0
rs7719775	RICTOR		0.00	0
rs7703002	RICTOR		0.00	0

ChEMBL bioactivities

125 potent at pChembl≥5 of 128 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.74	IC50	0.18	nM	OMIPALISIB
9.52	Ki	0.3	nM	OMIPALISIB
9.00	IC50	1	nM	CHEMBL4563142
9.00	IC50	1	nM	CHEMBL5219718
8.96	IC50	1.1	nM	CHEMBL5218727
8.92	IC50	1.2	nM	CHEMBL5218916
8.82	IC50	1.5	nM	CHEMBL5219710
8.70	IC50	2	nM	TORIN1
8.66	IC50	2.2	nM	CHEMBL5218988
8.62	IC50	2.4	nM	CHEMBL5220152
8.57	IC50	2.7	nM	CHEMBL5220536
8.55	IC50	2.8	nM	AZD-8055
8.55	IC50	2.8	nM	CHEMBL5220948
8.30	IC50	5	nM	CHEMBL561708
8.30	IC50	5	nM	CHEMBL4564479
8.30	IC50	5	nM	SAPANISERTIB
8.30	IC50	5	nM	CHEMBL5433283
8.23	IC50	5.9	nM	CHEMBL5218590
8.20	IC50	6.3	nM	CHEMBL5220383
8.15	IC50	7	nM	CHEMBL5427469
8.15	IC50	7	nM	CHEMBL5661831
8.05	IC50	9	nM	CHEMBL5424319
8.05	IC50	9	nM	CHEMBL5416106
8.00	IC50	10	nM	Ku-0063794
8.00	IC50	10	nM	TORIN1
7.96	IC50	11	nM	CHEMBL4529672
7.94	IC50	11.4	nM	CHEMBL5220500
7.92	IC50	12	nM	CHEMBL5410824
7.89	IC50	13	nM	CHEMBL5420465
7.85	IC50	14	nM	CHEMBL5404567
7.83	IC50	14.8	nM	CHEMBL4577549
7.79	IC50	16.3	nM	CHEMBL5221072
7.77	IC50	17	nM	CHEMBL4744705
7.77	IC50	17	nM	CHEMBL5404042
7.75	IC50	18	nM	CHEMBL5399022
7.70	IC50	20	nM	CHEMBL4572049
7.70	IC50	20	nM	CHEMBL4549761
7.68	IC50	21	nM	CHEMBL5425570
7.58	IC50	26	nM	CHEMBL5394726
7.52	IC50	30	nM	CHEMBL5400543
7.47	IC50	34	nM	CHEMBL4744705
7.46	IC50	35	nM	CHEMBL4445573
7.42	IC50	38	nM	CHEMBL4540705
7.40	IC50	40	nM	CHEMBL2348865
7.38	IC50	42	nM	CHEMBL5395211
7.34	IC50	46	nM	CHEMBL2348864
7.32	IC50	48	nM	CHEMBL5394891
7.29	IC50	51	nM	CHEMBL5422640
7.27	IC50	54	nM	CHEMBL5218488
7.26	IC50	55	nM	CHEMBL5426138

PubChem BioAssay actives

125 with measured affinity, of 263 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)-3-pyridinyl]benzenesulfonamide	1871789: Inhibition of mTORC2 (unknown origin)	ic50	0.0002	uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(1-methylcyclobutyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0010	uM
3-[(E)-4-(1,3-benzodioxol-5-yl)-2-oxobut-3-enyl]-3-hydroxy-1H-indol-2-one	1512673: Inhibition of mTORC2 (unknown origin)	ic50	0.0010	uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0011	uM
3-(2-amino-4-fluoro-1,3-benzoxazol-5-yl)-1-(2,2-dimethylbutyl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0012	uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-[(2S)-4-methylpentan-2-yl]pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0015	uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one	1994243: Inhibition of mTORC2 (unknown origin)	ic50	0.0020	uM
5-[4-amino-7-methyl-7-(2-methylpropyl)-6H-pyrrolo[3,2-d]pyrimidin-5-yl]-1,3-benzoxazol-2-amine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0022	uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-(2,2-dimethylpropyl)pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0024	uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-[(1-methylcyclobutyl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0027	uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-[(3-methylthietan-3-yl)methyl]pyrazolo[3,4-d]pyrimidine-4,6-diamine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0028	uM
[5-[2,4-bis[(3S)-3-methylmorpholin-4-yl]pyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol	1512673: Inhibition of mTORC2 (unknown origin)	ic50	0.0028	uM
5-(6-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine	1611626: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay	ic50	0.0050	uM
(6aS)-5-[1-(3-hydroxypropyl)cyclopropyl]-6a-methyl-2-(7-methyl-1H-indol-3-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0050	uM
methyl 4-[6-[4-(methoxycarbonylamino)phenyl]-4-morpholin-4-ylpyrazolo[5,4-d]pyrimidin-1-yl]piperidine-1-carboxylate	1512673: Inhibition of mTORC2 (unknown origin)	ic50	0.0050	uM
Sapanisertib	1611626: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay	ic50	0.0050	uM
N-[5-[4,6-diamino-1-(2,2-dimethylbutyl)pyrazolo[3,4-d]pyrimidin-3-yl]-1,3-benzoxazol-2-yl]acetamide	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0059	uM
5-[4-amino-7-methyl-7-(methylsulfanylmethyl)-6H-pyrrolo[3,2-d]pyrimidin-5-yl]-1,3-benzoxazol-2-amine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0063	uM
(6aS)-5-(4-hydroxycyclohexyl)-6a-methyl-2-(7-methyl-1H-indol-3-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0070	uM
4-[8-amino-1-(7-chloro-1H-indol-2-yl)imidazo[1,5-a]pyrazin-3-yl]cyclohexane-1-carboxylic acid	2151059: Competitive inhibition of mTORC2 immunoprecipitated from human HeLa cells using His-tagged 4E-BP1 as substrate incubated for 30 mins in presence of ATP by chemiluminescence based ELISA	ic50	0.0070	uM
(6aS)-6a-methyl-2-(7-methyl-1H-indol-3-yl)-5-(oxan-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0090	uM
[5-[2-[(2S,6R)-2,6-dimethylmorpholin-4-yl]-4-morpholin-4-ylpyrido[2,3-d]pyrimidin-7-yl]-2-methoxyphenyl]methanol	1512682: Inhibition of mTORC2 in HEK293 cells using GST-tagged S6K1 or Akt1 as substrate after 30 mins by immunoblotting assay	ic50	0.0100	uM
9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one	1512675: Inhibition of N-terminally FLAG-tagged mTORC2 (unknown origin) expressed in human HeLa cells using S6K1 or Akt1 as substrate after 20 mins by immunoblotting assay	ic50	0.0100	uM
3-(2-amino-1,3-benzoxazol-5-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidine-4,6-diamine	1611626: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay	ic50	0.0110	uM
5-[4-amino-7-(2-methylpropyl)-6,7-dihydropyrrolo[3,2-d]pyrimidin-5-yl]-1,3-benzoxazol-2-amine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0114	uM
(6aS)-5-(4-hydroxycyclohexyl)-6a-methyl-2-(7-methyl-1H-indol-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0120	uM
(6aS)-5-(4-hydroxycyclohexyl)-2-(1H-indol-4-yl)-6a-methyl-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0130	uM
1-[4-[7,7-dimethyl-4-[(3S)-3-methylmorpholin-4-yl]-6,6-dioxo-5H-thieno[3,4-d]pyrimidin-2-yl]phenyl]-3-ethylurea	1632682: Inhibition of mTORC2 in HEK293T/17 cells assessed as reduction in Akt phosphorylation at Ser-473 residue after 2 hrs by sandwich immunoassay	ic50	0.0148	uM
5-(4-amino-7-ethyl-7-methyl-6H-pyrrolo[3,2-d]pyrimidin-5-yl)-1,3-benzoxazol-2-amine	1916694: Inhibition of mTORC2 in human A-431 cells assessed as phosphorylated AKT level incubated for 3 hrs by HTRF assay	ic50	0.0163	uM
4-(difluoromethyl)-5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)pyrimidin-2-amine	1673841: Inhibition of mTORC2 in human A2058 cells assessed as reduction in PKB phosphorylation at S473 residue incubated for 1 hr by Western blot analysis	ic50	0.0170	uM
(6aS)-6a-methyl-5-(oxan-4-yl)-2-(1H-pyrrolo[2,3-c]pyridin-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0170	uM
5-(6-amino-4-chloro-1-propan-2-ylpyrazolo[5,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine	1611626: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay	ic50	0.0200	uM
5-(6-amino-1-butyl-4-chloropyrazolo[5,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine	1611626: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay	ic50	0.0200	uM
(6aS)-2-(1H-indol-4-yl)-6a-methyl-5-(oxan-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0210	uM
(6aS)-6a-methyl-2-(7-methyl-1H-indol-4-yl)-5-(oxan-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0260	uM
(6aS)-2-(1H-indol-3-yl)-6a-methyl-5-(oxan-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0300	uM
4-(difluoromethyl)-5-[4-[(3S)-3-methylmorpholin-4-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]pyrimidin-2-amine	1916669: Inhibition of mTORC2 (unknown origin)	ic50	0.0350	uM
1-[4-[(6aS)-5-(cyclopropylmethyl)-6a-methyl-6-oxo-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0380	uM
3-[2-(oxan-4-yl)ethyl]-5-[4-(1H-1,2,4-triazol-5-yl)phenyl]-1H-imidazo[4,5-b]pyrazin-2-one	1916669: Inhibition of mTORC2 (unknown origin)	ic50	0.0400	uM
1-[4-[(6aS)-6a-methyl-5-(oxan-4-yl)-6-oxo-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-2-yl]phenyl]-3-cyclopropylurea	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0420	uM
8-[2-(oxan-4-yl)ethyl]-2-[4-(1H-1,2,4-triazol-5-yl)phenyl]-5,7-dihydropyrazino[2,3-b]pyrazin-6-one	1916669: Inhibition of mTORC2 (unknown origin)	ic50	0.0460	uM
(6aS)-6a-methyl-2-(7-methyl-1H-pyrrolo[2,3-c]pyridin-4-yl)-5-(oxan-4-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0480	uM
(6aS)-5-(cyclopropylmethyl)-6a-methyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0510	uM
4-(difluoromethyl)-5-[4-(3,3-dimethylmorpholin-4-yl)-6-morpholin-4-yl-1,3,5-triazin-2-yl]pyridin-2-amine	1916669: Inhibition of mTORC2 (unknown origin)	ic50	0.0540	uM
(6aS)-5-(1-acetylpiperidin-4-yl)-2-(1H-indol-4-yl)-6a-methyl-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0550	uM
(6aS)-5-(3-methoxypropyl)-6a-methyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0570	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	2091793: Inhibition of mTORC2 (unknown origin) in presence of [gamma-32P]ATP by radioactivity based kinase assay	ic50	0.0580	uM
5-(6-amino-4-bromo-1-propan-2-ylpyrazolo[5,4-d]pyrimidin-3-yl)-1,3-benzoxazol-2-amine	1611626: Inhibition of mTORC2 in human A431 cells assessed as AKT phosphorylation at S473 residue incubated for 3 hrs by HTRF assay	ic50	0.0600	uM
(6aS)-5-[1-(2-hydroxyethyl)cyclopropyl]-6a-methyl-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0610	uM
(6aS)-6a-methyl-5-(oxan-4-yl)-2-(1H-pyrrolo[2,3-b]pyridin-5-yl)-9,10-dihydro-7H-[1,4]oxazino[3,4-h]pteridin-6-one	2021628: Inhibition of mTORC2 in human PC-3 cells assessed as AKT phosphorylation at S473 residue in incubated for 1 hr by Alphascreen assay	ic50	0.0620	uM

CTD chemical–gene interactions

56 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression, decreases methylation	5
Pioglitazone	affects cotreatment, decreases expression, decreases reaction, increases expression	2
tert-Butylhydroperoxide	affects expression, affects cotreatment, decreases expression, decreases reaction, increases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
moringin	affects cotreatment, increases expression	1
oxybenzone	increases expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
beta-lapachone	decreases expression	1
arsenite	affects binding, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	decreases expression	1
tetrathiomolybdate	decreases expression	1
4-phenylenediamine	decreases expression	1
nickel sulfate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	increases expression, increases ubiquitination	1
entinostat	decreases expression	1
SB 216763	decreases reaction, increases expression	1
Chir 99021	increases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases response to substance, increases expression	1
pevonedistat	increases expression	1
jinfukang	decreases expression	1
Rosiglitazone	decreases reaction, increases expression	1
Sunitinib	decreases expression	1
Troglitazone	increases expression, affects cotreatment, decreases expression, decreases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	increases expression	1

ChEMBL screening assays

99 unique, capped per target: 99 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1832063	Binding	Inhibition of mTORC2 in human PC3 cells assessed as SGK1 phosphorylation by Western blot analysis	Identification and characterization of a novel integrin-linked kinase inhibitor. — J Med Chem

Cellosaurus cell lines

7 cell lines: 5 cancer cell line, 1 transformed cell line, 1 spontaneously immortalized cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1H9	Abcam A-549 RICTOR KO	Cancer cell line	Male
CVCL_B8NU	Abcam HCT 116 RICTOR KO	Cancer cell line	Male
CVCL_B9B6	Abcam MCF-7 RICTOR KO	Cancer cell line	Female
CVCL_D9QH	Ubigene HEK293 RICTOR KO	Transformed cell line	Female
CVCL_RR12	MCF10A RICTOR (-/-)	Spontaneously immortalized cell line	Female
CVCL_TI99	HAP1 RICTOR (-) 1	Cancer cell line	Male
CVCL_TJ00	HAP1 RICTOR (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

374 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome