DEPTOR

Summary

DEPTOR (DEP domain containing MTOR interacting protein, HGNC:22953) is a protein-coding gene on chromosome 8q24.12, encoding DEP domain-containing mTOR-interacting protein (Q8TB45). Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes.

Enables phosphatidic acid binding activity and protein serine/threonine kinase inhibitor activity. Involved in several processes, including negative regulation of TOR signaling; negative regulation of cell size; and negative regulation of protein kinase activity. Is active in lysosomal membrane.

Source: NCBI Gene 64798 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 87 total
• Druggable target: yes
• MANE Select transcript: NM_022783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22953
Approved symbol	DEPTOR
Name	DEP domain containing MTOR interacting protein
Location	8q24.12
Locus type	gene with protein product
Status	Approved
Aliases	DEP.6, FLJ12428
Ensembl gene	ENSG00000155792
Ensembl biotype	protein_coding
OMIM	612974
Entrez	64798

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000286234, ENST00000518057, ENST00000523492, ENST00000896811, ENST00000896812, ENST00000896813

RefSeq mRNA: 2 — MANE Select: NM_022783 NM_001283012, NM_022783

CCDS: CCDS6331, CCDS64960

Canonical transcript exons

ENST00000286234 — 9 exons

Exon	Start	End
ENSE00001022724	119929815	119929938
ENSE00001090742	119965232	119965410
ENSE00001195584	119928400	119928578
ENSE00001267564	120049576	120050918
ENSE00003474111	120001525	120001710
ENSE00003526727	120002977	120003111
ENSE00003549897	120006805	120006875
ENSE00003657207	120009029	120009133
ENSE00003845702	119873722	119873968

Expression profiles

Bgee: expression breadth ubiquitous, 282 present calls, max score 98.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.7111 / max 472.4326, expressed in 1275 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
90404	6.9024	1061
90406	2.6193	664
90408	2.3916	710
90403	0.8826	365
90407	0.7788	416
90409	0.5804	280
90405	0.5561	294

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	98.85	gold quality
decidua	UBERON:0002450	98.16	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	98.16	gold quality
gluteal muscle	UBERON:0002000	98.05	gold quality
vastus lateralis	UBERON:0001379	97.99	gold quality
biceps brachii	UBERON:0001507	97.85	gold quality
quadriceps femoris	UBERON:0001377	97.62	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	97.62	gold quality
skeletal muscle tissue	UBERON:0001134	97.52	gold quality
triceps brachii	UBERON:0001509	97.32	gold quality
muscle organ	UBERON:0001630	96.70	gold quality
hair follicle	UBERON:0002073	96.70	gold quality
gastrocnemius	UBERON:0001388	96.61	gold quality
deltoid	UBERON:0001476	96.57	gold quality
diaphragm	UBERON:0001103	96.54	gold quality
cardia of stomach	UBERON:0001162	96.36	gold quality
muscle of leg	UBERON:0001383	96.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	95.95	gold quality
body of tongue	UBERON:0011876	95.81	gold quality
right adrenal gland cortex	UBERON:0035827	95.55	gold quality
adrenal cortex	UBERON:0001235	95.06	gold quality
right adrenal gland	UBERON:0001233	94.91	gold quality
left adrenal gland	UBERON:0001234	94.82	gold quality
left adrenal gland cortex	UBERON:0035825	94.76	gold quality
adrenal gland	UBERON:0002369	94.61	gold quality
nephron tubule	UBERON:0001231	94.51	gold quality
muscle tissue	UBERON:0002385	94.26	gold quality
pylorus	UBERON:0001166	94.13	gold quality
tibialis anterior	UBERON:0001385	94.12	gold quality
renal medulla	UBERON:0000362	94.03	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	45.96
E-MTAB-6701	yes	20.31
E-MTAB-6678	yes	10.34
E-CURD-112	yes	8.66
E-GEOD-83139	yes	4.17
E-GEOD-124858	no	56.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): IL1B

miRNA regulators (miRDB)

98 targeting DEPTOR, 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-MIR-4262	100.00	73.26	3931
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-6740-5P	100.00	65.64	932
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-1297	99.91	73.41	3162

Literature-anchored findings (GeneRIF, showing 40)

• DEPTOR is highly overexpressed in a subset of multiple myelomas harboring cyclin D1/D3 or c-MAF/MAFB translocations. (PMID:19446321)
• High expression levels of DEPTOR are predictive of response to thalidomide in myeloma. (PMID:20858096)
• DEPTOR is a novel prognostic marker for differentiated thyroid carcinoma. (PMID:21643629)
• These novel findings are indicative of a higher order of complexity of DEPTOR signalling in the human placenta that is affected by maternal stress. (PMID:21992080)
• misregulation of the DEPTOR destruction pathway might contribute to aberrant activation of mTOR in disease. (PMID:22017875)
• DEPTOR, an mTOR inhibitor, is a physiological substrate of SCF(betaTrCP) E3 ubiquitin ligase and regulates survival and autophagy (PMID:22017876)
• mTOR generates an auto-amplification loop by triggering the betaTrCP- and CK1alpha-dependent degradation of DEPTOR. (PMID:22017877)
• GNMT regulates hepatocellular carcinoma growth in part through interacting with DEPDC6/DEPTOR and modulating mTOR/raptor signaling pathway (PMID:22160218)
• Raf-1/JNK /p53/p21 pathway may be involved in apoptosis, and NFkappaB1 may play a possible role in inhibiting apoptosis. (PMID:22282237)
• this review discusses beta-TrCP’s new downstream substrate, DEPTOR, as well as summarize the novel functional aspects of beta-TrCP in controlling cell growth and regulating autophagy, in part through governing the stability of DEPTOR.[Review] (PMID:22454292)
• the downregulation of DEPTOR induces apoptosis, increases chemosensitivity to doxorubicin, and suppresses autophagy and the activation of the PI3K/Akt signaling pathway in RPMI8226 human multiple myeloma cells. (PMID:23503641)
• There is a significant downregulation of mTOR, DEPTOR, and Raptor in preterm labouring myometria when compared to non-pregnant tissues taken from the same area. (PMID:23541542)
• Deptor is induced by the Baf60c-Six4 transcriptional complex and mediates activation of Akt and glycolytic metabolism by Baf60c in a cell-autonomous manner (PMID:23563706)
• Downregulation of DEPTOR inhibited proliferation and increased chemosensitivity to melphalan in human multiple myeloma RPMI-8226 cells via inhibiting the PI3K/AKT pathway. (PMID:23613505)
• these findings define DEPTOR as a critical upstream regulator of endothelial cell activation responses. (PMID:23881914)
• Downregulation of DEPTOR (p=0.331) in CRC. (PMID:24969890)
• In Alzheimer’s disease patients the mTOR pathway can be overactive, leading to a dysfunction of autophagy and a lack of amyloid beta clearance so the excess of amyloid beta will cause a further decrease in DEPTOR and an increase in mTOR expression. (PMID:25119265)
• DEPTOR plays a key role in maintaining stem cell pluripotency by limiting mTOR activity in undifferentiated embryonic stem cells (PMID:25258312)
• our data provide evidence for the requirement of TGFbeta-activated mTORC1 only by deptor downregulation, which dominates upon the bystander mTORC2 activity for enhanced expression of collagen I (alpha2). (PMID:25333702)
• Data suggest that DEPTOR has a tumor suppressive activity against pancreatic cancer cells, and its loss of expression may contribute to pancreatic tumorigenesis. (PMID:25544749)
• Receptor CXCR4 signaling promotes lysosomal and ESCRT-dependent degradation of DEPTOR, an antagonist of mTORC2, that regulates Akt activation and signaling. (PMID:25605718)
• Deptor enhances triple-negative breast cancer metastasis and chemoresistance through coupling to survivin expression (PMID:25810016)
• conclude that DEPTOR-related mTOR suppression is involved in metformin’s anti-cancer action in liver, and could be a novel target for anti-cancer therapy (PMID:25843797)
• Data indicate that phosphatidic acid (PA) specifically disrupts DEPTOR-mTORC1 interaction. (PMID:25936805)
• Propose regulation of placental SNAT2/LAT1 ubiquitination by mTORC1 and Nedd4-2. (PMID:26608079)
• Cul1 promoted mTORC1 activity and cap-dependent translation by enhancing the ubiquitination and degradation of DEPTOR. (PMID:26717892)
• Association between insulin sensitivity and genetic variants in DEPTOR gene suggest DEPTOR and mammalian target of rapamycin signaling pathway to be potential target for future research and pharmacological interventions. (PMID:26871578)
• Low DEPTOR expression is associated with esophageal squamous cell carcinoma. (PMID:26893358)
• Results provide evidence that DEPTOR acts as a tumor suppressor by limiting EGFR-driven lung adenocarcinoma progression. (PMID:26896556)
• DEPTOR overexpression is associated with cervical squamous cell carcinoma. (PMID:26992219)
• In this study we began by validating the expression of four main mTOR pathway components, mTOR, DEPTOR, rictor and raptor, at gene and protein level in in vitro models of endometrioid (MDAH2774) and clear cell (SKOV3) ovarian cancer (PMID:27211906)
• High DEPTOR expression is associated with T-cell leukemia. (PMID:27593934)
• Deptor depletion induces endoplasmic reticulum (ER) stress and synergizes the effect of the proteasome inhibitor bortezomib (Bz) in multiple myeloma (MM) cells. (PMID:27655709)
• Studies provide evidence that Deptor appears to play an important role in the pathogenesis of many types of cancers, mainly through its role in controlling the activity of mTOR and many other possible functions. [review] (PMID:28086984)
• High expression of DEPTOR benefits esophageal squamous cell carcinoma patients in early stage but not advanced stage. (PMID:28267437)
• the present findings supported the fact that DEPTOR-mTOR signaling is a central regulator of lipid metabolism-mediated inflammation in lymphocytes of PBMC culture. (PMID:28349073)
• In ASS1-knockout cells, DEPTOR, an inhibitor of mTORC1 signal, was downregulated and mTORC1 signaling was more activated in response to arginine. (PMID:28358054)
• that DEPTOR expression is required to maintain myeloma cell differentiation and high level of its expression are associated with better outcome. (PMID:28420429)
• Using computational modeling, systems analysis and dynamic simulations, study shows that DEPTOR confers remarkably rich and complex dynamic behaviours to mTOR signalling, including abrupt, bistable switches, oscillations and co-existing bistable/oscillatory responses. Transitions between these distinct modes of behavior are enabled by modulating DEPTOR expression alone. (PMID:29330362)
• findings reveal a mechanism that stabilizes the mTORC1 inhibitor DEPTOR via OTUB1’s deubiquitinase activity. (PMID:29382726)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	deptor	ENSDARG00000040930
mus_musculus	Deptor	ENSMUSG00000022419
rattus_norvegicus	Deptor	ENSRNOG00000004328

Paralogs (3): PREX2 (ENSG00000046889), PREX1 (ENSG00000124126), GPR155 (ENSG00000163328)

Protein

Protein identifiers

DEP domain-containing mTOR-interacting protein — Q8TB45 (reviewed: Q8TB45)

Alternative names: DEP domain-containing protein 6

All UniProt accessions (1): Q8TB45

UniProt curated annotations — full annotation on UniProt →

Function. Negative regulator of the mTORC1 and mTORC2 complexes: inhibits the protein kinase activity of MTOR, thereby inactivating both complexes. DEPTOR inhibits mTORC1 and mTORC2 to induce autophagy. In contrast to AKT1S1/PRAS40, only partially inhibits mTORC1 activity.

Subunit / interactions. Associated component of the mechanistic target of rapamycin complex 1 (mTORC1) which contains MTOR, MLST8 and RPTOR. Associated component of the mechanistic target of rapamycin complex 2 (mTORC2) which contains MTOR, MLST8, PROTOR1, RICTOR, MAPKAP1 and DEPTOR. Interacts (via PDZ domain) with MTOR; interacts with MTOR within both mTORC1 and mTORC2. Interacts (via PDZ domain) with MINAR1 (via N-terminus). Interacts with SIK3.

Subcellular location. Lysosome membrane.

Post-translational modifications. Phosphorylation weakens interaction with MTOR within mTORC1 and mTORC2. Phosphorylated at Ser-286, Ser-287 and Ser-291 in response to mitogenic stimulation by MTOR: DEPTOR is either directly phosphorylated by MTOR or indirectly via proteins kinases that are activated by MTOR, such as CK1/CSNK1A1. Phosphorylation at Ser-286, Ser-287 and Ser-291 promotes ubiquitination by the SCF(BTRC) complex, followed by degradation. Phosphorylation at Ser-235 by MAPK3/ERK1 promotes deubiquitination by USP7, enhancing its stability. Phosphorylation at Tyr-289 by SYK impairs its interaction with MTOR, promoting mTORC1 and mTORC2 signaling. Ubiquitinated; leading to proteasomal degradation. Ubiquitination by the SCF(BTRC) and SCF(FBXW11) complexes following phosphorylation at Ser-286, Ser-287 and Ser-291 by MTOR, leads to its degradation by the proteasome. Deubiquitinated by OTUB1 in response to amino acid via a non-canonical mechanism, leading to DEPTOR stability. Deubiquitinated by USP7 following phosphorylation at Ser-235, promoting its stability.

Activity regulation. Inhibited upon phosphatidic acid-binding: phosphatidic acid produced upon mitogenic stimulation promotes DEPTOR dissociatiom from the mTORC1 and mTORC2 complexes, leading to their activation. Specifically binds unsaturated phosphatidic acid, such as 16:0-18:1, 18:0-18:1 and di-18:1. Inhibited when nutrients are present via a feedback loop: phosphorylation by MTOR promotes DEPTOR ubiquitination and degradation.

Induction. Expression is negatively regulated by both mTORC1 and mTORC2 (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
Q8TB45-1	1	yes
Q8TB45-2	2

RefSeq proteins (2): NP_001269941, NP_073620* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000591	DEP_dom	Domain
IPR001478	PDZ	Domain
IPR036034	PDZ_sf	Homologous_superfamily
IPR036388	WH-like_DNA-bd_sf	Homologous_superfamily
IPR036390	WH_DNA-bd_sf	Homologous_superfamily
IPR037335	DEPTOR_DEP_1	Domain
IPR037336	DEPTOR_DEP_2	Domain
IPR051832	mTOR-Rac_regulators	Family

Pfam: PF00610

UniProt features (90 total): mutagenesis site 27, modified residue 20, strand 19, helix 11, domain 3, sequence variant 3, short sequence motif 2, sequence conflict 2, chain 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
7DKL	X-RAY DIFFRACTION	1.5
7PED	X-RAY DIFFRACTION	1.93
7PE8	ELECTRON MICROSCOPY	3.2
7PE7	ELECTRON MICROSCOPY	3.41
7PEB	ELECTRON MICROSCOPY	3.67
7PE9	ELECTRON MICROSCOPY	3.7
7PEA	ELECTRON MICROSCOPY	4.07
7PEC	ELECTRON MICROSCOPY	4.24
7OWG	ELECTRON MICROSCOPY	4.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TB45-F1	81.11	0.57

Functional residue map

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

Post-translational modifications (20): 244, 258, 259, 263, 265, 280, 282, 283, 286, 287, 289, 291, 293, 295, 297, 298, 299, 1, 235, 241

Mutagenesis-validated functional residues (27):

Position	Phenotype
53	decreased phosphatidic acid-binding.
54	decreased phosphatidic acid-binding.
58	decreased phosphatidic acid-binding.
225	decreased phosphatidic acid-binding.
231	decreased phosphatidic acid-binding.
235	decreased phosphorylation, leading to impaired deubiquitination by usp7.
235	mimics phosphorylation, leading to slightly increased stability.
241	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
244	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
258	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
259	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
263	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
265	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
282	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
283	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
286–291	mimics phosphorylation; promoting association with the scf(btrc) complex.
286	reduced ubiquitination by the scf(btrc) complex.
287	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
289	mimics phosphorylation, leading to slightly decreased interaction with mtor.
289	decreased phosphorylation, leading to increased interaction with mtor.
291	reduced ubiquitination by the scf(btrc) complex.
293	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
295–299	reduced ubiquitination by the scf(btrc) complex.
297	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho
298	in mutant 13a; abolished phosphorylation, leading to promote interaction with mtor without affecting ability to bind pho

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 293 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_DN, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_REGULATION_OF_AUTOPHAGY, KOBAYASHI_EGFR_SIGNALING_24HR_UP, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, GOCC_VACUOLAR_MEMBRANE, GCANCTGNY_MYOD_Q6, GOZGIT_ESR1_TARGETS_DN, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN

GO Biological Process (13): negative regulation of protein kinase activity (GO:0006469), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of autophagy (GO:0010508), negative regulation of TOR signaling (GO:0032007), intracellular signal transduction (GO:0035556), negative regulation of cell size (GO:0045792), negative regulation of TORC2 signaling (GO:1903940), negative regulation of TORC1 signaling (GO:1904262), regulation of extrinsic apoptotic signaling pathway (GO:2001236), autophagosome assembly (GO:0000045), negative regulation of autophagy (GO:0010507), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202)

GO Molecular Function (7): protein kinase inhibitor activity (GO:0004860), guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), protein serine/threonine kinase inhibitor activity (GO:0030291), phosphatidic acid binding (GO:0070300), protein binding (GO:0005515), lipid binding (GO:0008289)

GO Cellular Component (4): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), lysosome (GO:0005764), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	2
signal transduction	2
autophagy	2
regulation of autophagy	2
TOR signaling	2
negative regulation of TOR signaling	2
GTPase regulator activity	2
binding	2
negative regulation of protein phosphorylation	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
G protein-coupled receptor activity	1
positive regulation of catabolic process	1
regulation of TOR signaling	1
negative regulation of intracellular signal transduction	1
intracellular anatomical structure	1
regulation of cell size	1
TORC2 signaling	1
regulation of TORC2 signaling	1
TORC1 signaling	1
regulation of TORC1 signaling	1
extrinsic apoptotic signaling pathway	1
regulation of apoptotic signaling pathway	1
Atg12 activating enzyme activity	1
protein-phosphatidylethanolamide deconjugating activity	1
Atg12 conjugating enzyme activity	1
Atg12 ligase activity	1
organelle assembly	1
Atg1/ULK1 kinase complex assembly	1
autophagosome organization	1
negative regulation of catabolic process	1
response to nutrient levels	1
cellular response to stimulus	1
kinase inhibitor activity	1
protein kinase regulator activity	1
GTP binding	1
GDP binding	1
GTPase activity	1
enzyme activator activity	1
protein serine/threonine kinase activity	1

Protein interactions and networks

STRING

1380 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DEPTOR	MAPKAP1	Q9BPZ7	998
DEPTOR	PRR5	P85299	998
DEPTOR	RPTOR	Q8N122	998
DEPTOR	AKT1S1	Q96B36	998
DEPTOR	MLST8	Q9BVC4	998
DEPTOR	MTOR	P42345	997
DEPTOR	RICTOR	Q6R327	997
DEPTOR	TTI1	O43156	996
DEPTOR	PRR5L	Q6MZQ0	963
DEPTOR	FKBP8	Q14318	955
DEPTOR	TELO2	Q9Y4R8	947
DEPTOR	RPS6KB1	P23443	894
DEPTOR	RHEB	Q15382	882
DEPTOR	HSPA4	P34932	856
DEPTOR	SGK1	O00141	835

IntAct

42 interactions, top by confidence:

A	B	Type	Score
RPTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.980
RPTOR	MTOR	psi-mi:“MI:0914”(association)	0.980
MTOR	RICTOR	psi-mi:“MI:0915”(physical association)	0.970
RICTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.970
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
TRAF1	DEPTOR	psi-mi:“MI:0915”(physical association)	0.560
DEPTOR	CCDC110	psi-mi:“MI:0915”(physical association)	0.560
DEPTOR	TRAF1	psi-mi:“MI:0915”(physical association)	0.560
DEPTOR	ANKRD11	psi-mi:“MI:0915”(physical association)	0.560
MTOR	DEPTOR	psi-mi:“MI:0915”(physical association)	0.520
DEPTOR	MTOR	psi-mi:“MI:0915”(physical association)	0.520
Mtor	DEPTOR	psi-mi:“MI:0914”(association)	0.500
DEPTOR	Mtor	psi-mi:“MI:0915”(physical association)	0.500
ATP2B4	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
CYSLTR2	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
DGKK	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
DGKZ	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
FZD7	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
E6	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
ORF putative E6	DEPTOR	psi-mi:“MI:0407”(direct interaction)	0.440
DEPTOR	RALBP1	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (119): DEPTOR (Affinity Capture-MS), DEPTOR (Two-hybrid), CCDC110 (Two-hybrid), DEPTOR (Affinity Capture-RNA), DEPTOR (Affinity Capture-MS), DEPTOR (Biochemical Activity), DEPTOR (Two-hybrid), BTRC (Two-hybrid), TRIM41 (Two-hybrid), DEPTOR (Affinity Capture-MS), DEPTOR (Affinity Capture-Western), DEPTOR (Affinity Capture-Western), FBXW7 (Affinity Capture-Western), FBXW11 (Affinity Capture-Western), BTRC (Affinity Capture-Western)

ESM2 similar proteins: A1A5G4, A2ALK8, A8MUH7, A9CB74, F1M386, F1MSG6, F1PBJ0, O14745, O14907, O14936, O70589, P19878, P26045, P70290, P70441, P70600, Q00013, Q09506, Q14289, Q17QN6, Q28619, Q3SZK8, Q3T0X8, Q4L1J4, Q4R6G4, Q570Y9, Q5F488, Q5RCF7, Q5RDW4, Q5T2W1, Q5TCQ9, Q5ZIJ9, Q5ZJ00, Q60629, Q62915, Q69ZS7, Q6RHR9, Q865P3, Q8CHG7, Q8TB45

Diamond homologs: A1CEE0, A1DFV9, A4R596, O75140, P61460, Q0CHV5, Q1E9Q9, Q2H0S0, Q2UMR9, Q4WHH4, Q54XA2, Q570Y9, Q5AW24, Q7S9J6, Q8TB45, Q8WZA2, Q9W0E3, A2AWR3, Q3LAC4, Q4PE51, Q5R9A7, Q69ZK0, Q6CWI2, Q70Z35, Q7Z3F1, Q8TCU6, Q9EQZ6, A1A5G4, A5PKA5, A8JQ65, A8MUH7, B3LXF2, B3NYS4, B4I4Y1, B4JHJ7, B4K6T8, B4PRE2, B4R0A5, B7WN72, D3YXJ0

SIGNOR signaling

25 interactions.

A	Effect	B	Mechanism
MTOR	down-regulates	DEPTOR	phosphorylation
RPS6KB1	down-regulates	DEPTOR	phosphorylation
CSNK1A1	down-regulates	DEPTOR	phosphorylation
RPS6KA1	down-regulates	DEPTOR	phosphorylation
DEPTOR	“form complex”	mTORC1	binding
DEPTOR	“form complex”	mTORC2	binding
DEPTOR	“down-regulates activity”	MTOR	binding
DEPTOR	“down-regulates activity”	mTORC1	binding
DEPTOR	“down-regulates activity”	mTORC2	binding
RPS6K	down-regulates	DEPTOR	phosphorylation
RNF7	“down-regulates activity”	DEPTOR	ubiquitination
SYK	“down-regulates activity”	DEPTOR	phosphorylation
CHKA	“down-regulates quantity by destabilization”	DEPTOR	phosphorylation
MAPK3	“up-regulates quantity by stabilization”	DEPTOR	phosphorylation
USP7	“up-regulates quantity by stabilization”	DEPTOR	deubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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.

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cell growth	5	45.8×	6e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	63
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2671 predictions. Top by Δscore:

Variant	Effect	Δscore
8:119890743:A:AG	acceptor_gain	1.0000
8:119890743:AAAAT:A	acceptor_gain	1.0000
8:119890744:A:G	acceptor_gain	1.0000
8:119928398:A:AG	acceptor_gain	1.0000
8:119928398:AG:A	acceptor_gain	1.0000
8:119928399:G:GA	acceptor_gain	1.0000
8:119928399:GG:G	acceptor_gain	1.0000
8:119928399:GGC:G	acceptor_gain	1.0000
8:119928399:GGCT:G	acceptor_gain	1.0000
8:119928399:GGCTC:G	acceptor_gain	1.0000
8:119929802:T:G	acceptor_gain	1.0000
8:119929809:TTTCA:T	acceptor_loss	1.0000
8:119929811:TCA:T	acceptor_loss	1.0000
8:119929812:CA:C	acceptor_loss	1.0000
8:119929813:A:AG	acceptor_gain	1.0000
8:119929813:AGT:A	acceptor_gain	1.0000
8:119929813:AGTGT:A	acceptor_gain	1.0000
8:119929814:G:GG	acceptor_gain	1.0000
8:119929814:GT:G	acceptor_gain	1.0000
8:119929814:GTG:G	acceptor_gain	1.0000
8:119929814:GTGT:G	acceptor_gain	1.0000
8:119929814:GTGTG:G	acceptor_gain	1.0000
8:119929907:GCCTT:G	donor_gain	1.0000
8:119929927:GCTA:G	donor_gain	1.0000
8:119929934:GAAAA:G	donor_gain	1.0000
8:119929936:AAA:A	donor_gain	1.0000
8:119929936:AAAGT:A	donor_loss	1.0000
8:119929937:AA:A	donor_gain	1.0000
8:119929937:AAGT:A	donor_loss	1.0000
8:119929938:AGT:A	donor_loss	1.0000

AlphaMissense

2743 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:119873955:G:A	G37R	1.000
8:119873955:G:C	G37R	1.000
8:119873955:G:T	G37W	1.000
8:119873956:G:A	G37E	1.000
8:119873965:T:C	L40P	1.000
8:119928408:T:C	L44P	1.000
8:119928435:G:C	R53T	1.000
8:119928436:A:C	R53S	1.000
8:119928436:A:T	R53S	1.000
8:119928464:T:C	C63R	1.000
8:119928466:T:G	C63W	1.000
8:119928495:T:C	L73P	1.000
8:119929860:G:C	R116P	1.000
8:119929863:T:C	F117S	1.000
8:119929871:G:C	D120H	1.000
8:120009048:G:A	G339D	1.000
8:120009050:T:A	W340R	1.000
8:120009050:T:C	W340R	1.000
8:120009053:G:C	G341R	1.000
8:120009057:T:C	F342S	1.000
8:120009087:T:A	I352N	1.000
8:120009114:C:A	A361E	1.000
8:120049589:T:A	V372D	1.000
8:120049598:T:A	V375D	1.000
8:119873968:G:C	R41P	0.999
8:119928434:A:G	R53G	0.999
8:119928435:G:T	R53I	0.999
8:119928437:C:A	R54S	0.999
8:119928447:T:C	L57P	0.999
8:119928455:T:G	Y60D	0.999

dbSNP variants (sampled 300 via entrez): RS1000017333 (8:119895251 A>G), RS1000022216 (8:120035173 A>G), RS1000025658 (8:119966429 G>A,C), RS1000031136 (8:120010855 CATTGTTTTT>C), RS1000032938 (8:119935751 A>G), RS1000035153 (8:119915025 G>A), RS1000045425 (8:120020439 A>G), RS1000048898 (8:119916308 T>A,G), RS1000055545 (8:119972592 C>T), RS1000081512 (8:119896262 GAGAAAGCAAAGGCTT>G), RS1000089968 (8:120000837 G>A), RS1000108007 (8:119878559 C>A), RS1000167437 (8:119918663 G>A,C), RS1000168085 (8:119898281 C>A,T), RS1000172202 (8:120027248 A>AT)

Disease associations

OMIM: gene MIM:612974 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST002976_9	HIV-1 viral setpoint	3.000000e-06
GCST003090_5	Depressive and manic episodes in bipolar disorder	9.000000e-07
GCST003091_3	Depressive episodes in bipolar disorder	1.000000e-06
GCST006979_367	Heel bone mineral density	1.000000e-09
GCST008058_261	Estimated glomerular filtration rate	2.000000e-08
GCST008059_228	Estimated glomerular filtration rate	5.000000e-07
GCST009211_6	Choroid plexus volume	1.000000e-07
GCST009758_3	Idiopathic pulmonary fibrosis	2.000000e-11
GCST90002400_448	Plateletcrit	5.000000e-14
GCST90002402_52	Platelet count	5.000000e-13
GCST90002406_310	Reticulocyte fraction of red cells	4.000000e-10
GCST90020024_186	A body shape index	2.000000e-09

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0006319	HIV viral set point measurement
EFO:0007704	depressive episode measurement
EFO:0007705	manic episode measurement
EFO:0009270	heel bone mineral density
EFO:0000768	idiopathic pulmonary fibrosis
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL4105866 (SINGLE PROTEIN), CHEMBL4523674 (PROTEIN-PROTEIN INTERACTION)

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4871827	DEPTOR		0.00	0

ChEMBL bioactivities

8 potent at pChembl≥5 of 8 total, top 8 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.22	IC50	600	nM	CHEMBL4082200
6.22	IC50	600	nM	CHEMBL4076172
6.16	IC50	700	nM	CHEMBL4064715
6.10	IC50	800	nM	CHEMBL4060289
6.10	IC50	800	nM	CHEMBL4078352
5.89	IC50	1300	nM	CHEMBL4084658
5.89	IC50	1300	nM	CHEMBL1898589
5.03	Kd	9300	nM	CHEMBL4864193

PubChem BioAssay actives

1 with measured affinity, of 80 total; 1 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-(3,4-dichlorophenyl)-9-[(3-fluorophenyl)methyl]-3-hydroxy-8,10-dihydropyrano[2,3-f][1,3]benzoxazin-4-one	1774237: Binding affinity to fluorescent labelled DEPTOR (unknown origin) incubated for 10 mins by microscale thermophoresis assay	kd	9.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	8
Estradiol	decreases expression, increases expression, affects cotreatment	7
Valproic Acid	affects cotreatment, increases expression	6
Aflatoxin B1	affects expression, decreases expression, increases expression	5
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
sodium arsenite	decreases expression	2
entinostat	increases expression, affects cotreatment	2
belinostat	increases expression, affects cotreatment	2
Resveratrol	affects cotreatment, increases expression, decreases expression	2
Vorinostat	increases expression, affects cotreatment	2
Panobinostat	affects cotreatment, increases expression	2
Cisplatin	decreases expression, affects response to substance	2
Dexamethasone	increases expression, affects cotreatment	2
Ethinyl Estradiol	affects expression, increases expression	2
Nickel	decreases expression	2
Silicon Dioxide	decreases expression	2
Zearalenone	increases expression	2
Cyclosporine	decreases expression	2
Genistein	increases expression	2
aristolochic acid I	decreases expression	1
OTX015	decreases expression	1
4-hydroxyphenyl 4-isopropoxyphenylsulfone	increases expression	1
sotorasib	affects cotreatment, decreases expression	1
methylmercuric chloride	decreases expression	1
deoxynivalenol	decreases expression	1
trichostatin A	increases expression	1
sulforaphane	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1

ChEMBL screening assays

26 unique, capped per target: 26 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4047126	Binding	Inhibition of mTOR binding to DEPTOR in human RPMI8226 cells assessed as increase in mTORC2-associated AKT phosphorylation at S473 residue by Western blot analysis	Structure-activity relationship study of small molecule inhibitors of the DEPTOR-mTOR interaction. — Bioorg Med Chem Lett

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female
CVCL_B8US	Abcam MCF-7 DEPTOR KO	Cancer cell line	Female

Clinical trials (associated diseases)

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