MAPKAP1

Summary

MAPKAP1 (MAPK associated protein 1, HGNC:18752) is a protein-coding gene on chromosome 9q33.3, encoding Target of rapamycin complex 2 subunit MAPKAP1 (Q9BPZ7). 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. It is a selective cancer dependency (DepMap: 14.5% of cell lines).

This gene encodes a protein that is highly similar to the yeast SIN1 protein, a stress-activated protein kinase. Alternatively spliced transcript variants encoding distinct isoforms have been described. Alternate polyadenylation sites as well as alternate 3’ UTRs have been identified for transcripts of this gene.

Source: NCBI Gene 79109 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 14.5% of screened cell lines
• MANE Select transcript: NM_001006617

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18752
Approved symbol	MAPKAP1
Name	MAPK associated protein 1
Location	9q33.3
Locus type	gene with protein product
Status	Approved
Aliases	MGC2745, SIN1, MIP1
Ensembl gene	ENSG00000119487
Ensembl biotype	protein_coding
OMIM	610558
Entrez	79109

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 29 protein_coding, 5 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000265960, ENST00000350766, ENST00000373496, ENST00000373498, ENST00000373503, ENST00000373511, ENST00000394060, ENST00000394063, ENST00000420643, ENST00000427078, ENST00000433483, ENST00000437973, ENST00000444226, ENST00000448439, ENST00000468896, ENST00000473837, ENST00000483937, ENST00000496063, ENST00000496658, ENST00000497932, ENST00000898451, ENST00000898452, ENST00000898453, ENST00000898454, ENST00000898455, ENST00000898456, ENST00000898457, ENST00000898458, ENST00000915245, ENST00000915246, ENST00000915247, ENST00000960913, ENST00000960914, ENST00000960915, ENST00000960916, ENST00000960917

RefSeq mRNA: 6 — MANE Select: NM_001006617 NM_001006617, NM_001006618, NM_001006619, NM_001006620, NM_001006621, NM_024117

CCDS: CCDS35139, CCDS35140, CCDS35141, CCDS48020, CCDS6864

Canonical transcript exons

ENST00000265960 — 12 exons

Exon	Start	End
ENSE00003481464	125669818	125669907
ENSE00003510646	125484443	125484583
ENSE00003517281	125657651	125657799
ENSE00003553356	125559633	125559809
ENSE00003570005	125467972	125468109
ENSE00003660996	125585555	125585727
ENSE00003786776	125543059	125543168
ENSE00003788668	125444501	125444598
ENSE00003848727	125706971	125707208
ENSE00003890615	125437394	125439012
ENSE00003892181	125506310	125506417
ENSE00003894419	125672316	125672643

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 96.99.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.1731 / max 537.0286, expressed in 1824 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102506	49.3029	1823
102502	2.0515	491
102486	0.4968	97
102505	0.4580	220
102501	0.2621	79
102485	0.2360	74
102484	0.1576	57
102500	0.1035	42
102499	0.0569	24
102483	0.0355	9

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.99	gold quality
apex of heart	UBERON:0002098	96.46	gold quality
stromal cell of endometrium	CL:0002255	95.98	gold quality
oocyte	CL:0000023	95.95	gold quality
gastrocnemius	UBERON:0001388	95.78	gold quality
secondary oocyte	CL:0000655	95.76	gold quality
muscle of leg	UBERON:0001383	95.71	gold quality
right atrium auricular region	UBERON:0006631	95.51	gold quality
left adrenal gland cortex	UBERON:0035825	95.47	gold quality
heart left ventricle	UBERON:0002084	95.46	gold quality
right adrenal gland cortex	UBERON:0035827	95.43	gold quality
left adrenal gland	UBERON:0001234	95.35	gold quality
right adrenal gland	UBERON:0001233	95.34	gold quality
cardiac ventricle	UBERON:0002082	95.23	gold quality
left testis	UBERON:0004533	95.12	gold quality
right testis	UBERON:0004534	95.01	gold quality
ectocervix	UBERON:0012249	94.86	gold quality
lower esophagus	UBERON:0013473	94.78	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.78	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.78	gold quality
adrenal cortex	UBERON:0001235	94.73	gold quality
rectum	UBERON:0001052	94.58	gold quality
adrenal gland	UBERON:0002369	94.48	gold quality
heart	UBERON:0000948	94.29	gold quality
islet of Langerhans	UBERON:0000006	94.25	gold quality
gall bladder	UBERON:0002110	94.14	gold quality
cardiac atrium	UBERON:0002081	94.10	gold quality
nucleus accumbens	UBERON:0001882	94.09	gold quality
caudate nucleus	UBERON:0001873	94.08	gold quality
endocervix	UBERON:0000458	93.89	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2

miRNA regulators (miRDB)

67 targeting MAPKAP1, 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-3163	100.00	77.23	8605
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-518A-5P	99.70	69.01	2209
HSA-MIR-527	99.70	69.01	2209
HSA-MIR-1283	99.69	72.42	3009
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-12122	99.56	69.33	1672
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-486-5P	99.51	70.39	707
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-1207-5P	99.49	69.11	2983

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 36)

• Results demonstrate that Sin1 transcripts can use alternative polyadenylation signals and describe a number of Sin1 splice variants that potentially encode functionally different isoforms. (PMID:15363842)
• The human Sin1 proteins form a complex with Jun N-terminal kinase. (PMID:15722200)
• A novel MEKK2-interacting protein, Mip1, that regulates MEKK2 dimerization and activation by forming a complex with inactive and nonphosphorylated MEKK2, was identified. (PMID:15988011)
• Sin1 is necessary for the assembly of TORC2 and for its capacity to phosphorylate Akt/PKB. (PMID:16919458)
• 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)
• Sin1 may contribute to ATF-2 signaling specificity by acting as a nuclear scaffold. (PMID:17054722)
• These data suggest that Sin1 is a mammalian Ras-inhibitor. (PMID:17303383)
• MIP-1 delta expression is increased in RBM (RCC (Renal Cell Carcinoma) bone metastasis) relative to RCC and bone marrow, and may promote RBM-induced osteolysis by stimulating recruitment/differentiation of osteoclast precursors into mature osteoclasts (PMID:18316587)
• SIN1 and PCBP2 are generally coregulated with large numbers of genes implicated in both cell survival and death and in cellular stress responses, including RNA translation and processing (PMID:18687895)
• There is an increased mitochondrial dependence upon mTORC2 dependent cell growth due to PTEN loss (PMID:21170086)
• mSIN1 protein mediates SGK1 protein interaction with mTORC2 protein complex and is required for selective activation of the epithelial sodium channel (PMID:21757730)
• structures show that the C-termini of Avo1 and Sin1 both have the pleckstrin homology (PH) domain fold (PMID:22505404)
• SIN1 plays an important role in hepatocellular carcinoma invasion and metastasis by facilitating epithelial-mesenchymal transition. (PMID:23564492)
• 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)
• results reveal a Sin1-phosphorylation-dependent mTORC2 regulation, providing a potential molecular mechanism by which mutations in the mTORC1-S6K-Sin1 signalling axis might cause aberrant hyper-activation of the mTORC2-Akt pathway (PMID:24161930)
• DNA-PKcs-mTORC2(SIN1) association is required for UVB-induced Akt Ser-473 phosphorylation and cell survival. (PMID:24365180)
• Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient lymphangioleiomyomatosis cells. (PMID:24395886)
• mitogen-activated protein kinase associated protein 1 rs10118570 may be an important protective factor for developing better management strategies in lung squamous cell carcinoma. (PMID:24926550)
• MAPKAP1 may represent a novel anti-infection and anti-fibrogenesis genomic locus in chronic schistosomiasis japonica. (PMID:25153992)
• Akt phosphorylates SIN1 at T86, enhancing mTORC2 kinase activity, which leads to phosphorylation of Akt S473 by mTORC2, thereby catalyzing full activation of Akt. (PMID:26235620)
• SIN1 plays an important role in breast cancer. (PMID:27780891)
• SIN1 plays an important role in non-small cell lung cancer; SIN1 is a potential biomarker and a promising target in the treatment of NSCLC (PMID:27993679)
• Intracellular localization of mTORC2 component, mSin1, contributes to regulation of Akt phosphorylation. (PMID:28143890)
• This study provides evidence that Sin1, a known element of the mammalian target of rapamycin complex 2 (mTORC2), is required for Interferon-gamma-induced phosphorylation and activation of AKT and that such activation mediates downstream regulation of mTORC1 and its effectors. (PMID:28174303)
• In colorectal cancer tissues, the Sin1 protein but not mRNA was significantly upregulated while Pdcd4 protein was downregulated, suggesting that loss of Pdcd4 might correlate with Sin1 protein level but not mRNA level in colorectal cancer. (PMID:28692058)
• SIN1 interacted and co-located with PKC zeta by pleckstrin homology (PH) domain. Downregulation of SIN1 severely impaired PKC zeta translocation and phosphorylation induced by insulin. (PMID:28751630)
• Lysophosphatidic acids tabilizes mSin1 protein expression via JNK signaling by blocking its proteasomal degradation and identify the LPA/JNK/mSin1/mTORC/collagen I pathway as critical for fibrotic activation of mesenchymal cells. (PMID:30217824)
• Sin1 is an amplifier of platelet alphaIIbbeta3-mediated outsidein signaling and a susceptible sensor of hypoxia/ROS signaling in ischemic environments after myocardial infarction, inducing microthrombosis. (PMID:30571167)
• Genetic Predisposition to Glioma Mediated by a MAPKAP1 Enhancer Variant. (PMID:31773361)
• Sin1 promotes proliferation and invasion of prostate cancer cells by modulating mTORC2-AKT and androgen receptor signaling cascades. (PMID:32088212)
• G-Protein-Coupled Estrogen Receptor 1 Promotes Gender Disparities in Hepatocellular Carcinoma via Modulation of SIN1 and mTOR Complex 2 Activity. (PMID:32873626)
• RAS interaction with Sin1 is dispensable for mTORC2 assembly and activity. (PMID:34380736)
• Interactions between mTORC2 core subunits Rictor and mSin1 dictate selective and context-dependent phosphorylation of substrate kinases SGK1 and Akt. (PMID:35926713)
• Unmasking the tumourigenic role of SIN1/MAPKAP1 in the mTOR complex 2. (PMID:37877351)
• Overexpression of microRNA-611 inhibits TGF-beta-induced epithelial-mesenchymal transition and migration in lung cancer cells through MAPKAP1. (PMID:39173858)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	mapkap1	ENSDARG00000091777
mus_musculus	Mapkap1	ENSMUSG00000038696
rattus_norvegicus	Mapkap1	ENSRNOG00000017583
drosophila_melanogaster	Sin1	FBGN0033935
caenorhabditis_elegans		WBGENE00013261

Protein

Protein identifiers

Target of rapamycin complex 2 subunit MAPKAP1 — Q9BPZ7 (reviewed: Q9BPZ7)

Alternative names: Mitogen-activated protein kinase 2-associated protein 1, Stress-activated map kinase-interacting protein 1

All UniProt accessions (8): B1AMA5, B1AMA6, B1AMB1, B1AMB2, E9PGB8, Q9BPZ7, H0Y7F8, H0Y866

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, MAPKAP1/SIN1 acts as a substrate adapter which recognizes and binds AGC protein kinase family members for phosphorylation by MTOR. 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. MAPKAP1 inhibits MAP3K2 by preventing its dimerization and autophosphorylation. Inhibits HRAS and KRAS independently of mTORC2 complex. Enhances osmotic stress-induced phosphorylation of ATF2 and ATF2-mediated transcription. Involved in ciliogenesis, regulates cilia length through its interaction with CCDC28B independently of mTORC2 complex. In contrast to isoform 1, isoform 2 and isoform 6, isoform 4 is not a component of the a mTORC2 complex.

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. Interacts with MAP3K2. Interacts with ATF2. Interacts with MAPK8. Interacts with GTP-bound HRAS and KRAS; inhibiting their activity. Interacts with IFNAR2. Interacts with CCDC28B. Interacts with NBN.

Subcellular location. Cell membrane. Endoplasmic reticulum membrane. Early endosome membrane. Late endosome membrane. Lysosome membrane. Golgi apparatus membrane. Mitochondrion outer membrane. Cytoplasm. Perinuclear region. Nucleus Cell membrane. Cytosol Cytoplasm. Nucleus.

Tissue specificity. Ubiquitously expressed, with highest levels in heart and skeletal muscle.

Post-translational modifications. Phosphorylation at Ser-128 by PKC promotes relocalization to the perinuclear region, where the mTORC2 complex specifically mediates phosphorylation of SGK1. Phosphorylated at Thr-86 by AKT1 or RPS6KB1 in the presence of growth factors; the effect of this phosphorylation is however unclear. According to two studies, phosphorylation at Thr-86 by AKT1 is part of a positive feedback loop that increases mTORC2 activation. According to another study, phosphorylation at Thr-86 and Thr-398 by RPS6KB1 promotes dissociation from the mTORC2 complex, leading to inhibit mTORC2 signaling.

Activity regulation. Phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3) promotes MTOR activation by relieving MAPKAP1/SIN1-mediated inhibition of MTOR that takes place in absence of PI(3,4,5)P3.

Domain organisation. The CRIM domain forms a ubiquitin-like fold with a characteristic acidic loop, which recognizes and binds AGC protein kinase family members substrates. Arg-83 is required for the phosphorylation of SGK1, but not AKT (AKT1, AKT2 and AKT3): SGK1 promotes a large conformation change of the N-terminus of MAPKAP1/SIN1, promoting formation of a salt-bridge with RICTOR, leading to SGK1 phosphorylation. The SIN1-type PH binds phosphatidylinositol 3,4,5-trisphosphate (PI(3,4,5)P3). It plays a dual role in mTORC2: in absence of PI(3,4,5)P3, it binds and inactivates MTOR. PI(3,4,5)P3-binding relieves the inhibition, leading to mTORC2 activation.

Similarity. Belongs to the SIN1 family.

Isoforms (6)

UniProt ID	Names	Canonical?
Q9BPZ7-1	1, beta	yes
Q9BPZ7-2	2, alpha
Q9BPZ7-3	3
Q9BPZ7-4	4, delta
Q9BPZ7-5	5
Q9BPZ7-6	6, gamma

RefSeq proteins (6): NP_001006618, NP_001006619, NP_001006620, NP_001006621, NP_001006622, NP_077022 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR008828	Sin1/Avo1	Family
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR031313	Sin1_PH_dom	Domain
IPR031567	CRIM_dom	Domain
IPR032679	Sin1_N	Domain
IPR057339	RBD_SIN1	Domain

Pfam: PF05422, PF16978, PF16979, PF25322

UniProt features (70 total): strand 15, helix 14, modified residue 8, splice variant 7, mutagenesis site 6, sequence conflict 6, region of interest 4, binding site 3, domain 2, turn 2, initiator methionine 1, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
7VV9	X-RAY DIFFRACTION	1.6
7VV8	X-RAY DIFFRACTION	1.7
7VVB	X-RAY DIFFRACTION	1.7
7VVG	X-RAY DIFFRACTION	1.7
3VOQ	X-RAY DIFFRACTION	2
7LC1	X-RAY DIFFRACTION	2.35
9T94	ELECTRON MICROSCOPY	2.6
9ZBK	ELECTRON MICROSCOPY	2.6
7LC2	X-RAY DIFFRACTION	2.7
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-Q9BPZ7-F1	69.55	0.09

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 (3): 464; 393; 428

Post-translational modifications (8): 2, 86, 128, 186, 315, 356, 398, 510

Mutagenesis-validated functional residues (6):

Position	Phenotype
83	specifically abolishes ability of the mtorc2 complex to catalyze phosphorylation of sgk1, without affecting akt1.
236–244	decreased ability of the mtorc2 complex to catalyze phosphorylation of akt1.
287	does not affect interaction with kras.
291	decreased interaction with kras.
311	does not affect interaction with kras.
312	decreased interaction with kras.

Function

Pathways and Gene Ontology

Reactome pathways

28 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
R-HSA-1280218	Adaptive Immune System
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-168256	Immune System
R-HSA-194138	Signaling by VEGF
R-HSA-212436	Generic Transcription Pathway
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-3700989	Transcriptional Regulation by TP53
R-HSA-388841	Regulation of T cell activation by CD28 family
R-HSA-389356	Co-stimulation by CD28
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5633007	Regulation of TP53 Activity
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-6806003	Regulation of TP53 Expression and Degradation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers
R-HSA-9006934	Signaling by Receptor Tyrosine Kinases
R-HSA-9855142	Cellular responses to mechanical stimuli
R-HSA-9860931	Response of endothelial cells to shear stress

MSigDB gene sets: 230 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, TGCGCANK_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOCC_VACUOLAR_MEMBRANE, TTTGTAG_MIR520D, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOMF_GTPASE_BINDING, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, REACTOME_CO_STIMULATION_BY_CD28, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (15): cytoskeleton organization (GO:0007010), substantia nigra development (GO:0021762), positive regulation of cell growth (GO:0030307), cellular response to nutrient levels (GO:0031669), cellular response to insulin stimulus (GO:0032869), TORC2 signaling (GO:0038203), negative regulation of apoptotic process (GO:0043066), negative regulation of Ras protein signal transduction (GO:0046580), negative regulation of insulin receptor signaling pathway (GO:0046627), regulation of cellular response to oxidative stress (GO:1900407), ubiquitin-dependent protein catabolic process (GO:0006511), insulin receptor signaling pathway (GO:0008286), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), protein stabilization (GO:0050821), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)

GO Molecular Function (10): phosphatidylinositol-4,5-bisphosphate binding (GO:0005546), phosphatidylinositol-3,4,5-trisphosphate binding (GO:0005547), protein kinase binding (GO:0019901), small GTPase binding (GO:0031267), phosphatidylinositol-3,4-bisphosphate binding (GO:0043325), molecular adaptor activity (GO:0060090), phosphatidic acid binding (GO:0070300), phosphatidylinositol-3,5-bisphosphate binding (GO:0080025), enzyme-substrate adaptor activity (GO:0140767), protein binding (GO:0005515)

GO Cellular Component (23): Golgi membrane (GO:0000139), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), lysosome (GO:0005764), lysosomal membrane (GO:0005765), early endosome (GO:0005769), late endosome (GO:0005770), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), cilium (GO:0005929), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), TORC2 complex (GO:0031932), perinuclear region of cytoplasm (GO:0048471), mitochondrion (GO:0005739), endosome (GO:0005768), membrane (GO:0016020), serine/threonine protein kinase complex (GO:1902554)

Reactome top-level categories

Rollup of top-17 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
Immune System	1
Signaling by Receptor Tyrosine Kinases	1
RNA Polymerase II Transcription	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Generic Transcription Pathway	1
Adaptive Immune System	1
Regulation of T cell activation by CD28 family	1
Signaling by VEGF	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cytoplasm	5
intracellular membrane-bounded organelle	4
cellular anatomical structure	4
phosphatidylinositol phosphate binding	3
phosphatidylinositol bisphosphate binding	3
anion binding	2
binding	2
endosome	2
endomembrane system	2
endosome membrane	2
organelle organization	1
midbrain development	1
neural nucleus development	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
response to nutrient levels	1
cellular response to stimulus	1
response to insulin	1
cellular response to peptide hormone stimulus	1
TOR signaling	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
Ras protein signal transduction	1
regulation of Ras protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
cellular response to oxidative stress	1
regulation of cellular response to stress	1
regulation of response to oxidative stress	1
protein ubiquitination	1
modification-dependent protein catabolic process	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
intracellular signaling cassette	1

Protein interactions and networks

STRING

1826 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MAPKAP1	PRR5	P85299	999
MAPKAP1	RICTOR	Q6R327	999
MAPKAP1	MTOR	P42345	998
MAPKAP1	DEPTOR	Q8TB45	998
MAPKAP1	MLST8	Q9BVC4	998
MAPKAP1	PRR5L	Q6MZQ0	997
MAPKAP1	TTI1	O43156	995
MAPKAP1	RPTOR	Q8N122	992
MAPKAP1	AKT1S1	Q96B36	967
MAPKAP1	SGK1	O00141	851
MAPKAP1	TSC2	P49815	834
MAPKAP1	AKT1	P31749	814
MAPKAP1	RPS6KB1	P23443	779
MAPKAP1	RHEB	Q15382	754
MAPKAP1	EIF4EBP1	Q13541	753

IntAct

169 interactions, top by confidence:

A	B	Type	Score
RICTOR	MTOR	psi-mi:“MI:0914”(association)	0.970
MTOR	RICTOR	psi-mi:“MI:0914”(association)	0.970
MTOR	RICTOR	psi-mi:“MI:0403”(colocalization)	0.970
MAPKAP1	MTOR	psi-mi:“MI:0914”(association)	0.860
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
WDR5	MEN1	psi-mi:“MI:0914”(association)	0.710
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
KLHL22	TMEM223	psi-mi:“MI:0914”(association)	0.640
AKT1	MAPKAP1	psi-mi:“MI:0915”(physical association)	0.630
MAPKAP1	AKT1	psi-mi:“MI:2364”(proximity)	0.630
MAPKAP1	AKT1	psi-mi:“MI:0915”(physical association)	0.630
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAE	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
YWHAZ	PIK3C2A	psi-mi:“MI:0914”(association)	0.570
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
RPL26	RPL7	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530
CLEC11A	VWA8	psi-mi:“MI:0914”(association)	0.530
KCNE3	RIOK3	psi-mi:“MI:0914”(association)	0.530
PNMA2	CCDC85C	psi-mi:“MI:0914”(association)	0.530

BioGRID (263): MAPKAP1 (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MTOR (Affinity Capture-Western), RICTOR (Affinity Capture-Western), AKT1 (Biochemical Activity), AKT1 (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MAPKAP1 (Reconstituted Complex), MAPKAP1 (Affinity Capture-Western), NBN (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western), MAPKAP1 (Affinity Capture-Western)

ESM2 similar proteins: A0JN62, A2RT67, A2RUS2, A2VDU2, A4IFB6, A4IIM3, A7MBL8, B1H2P5, B4F779, O94967, P48553, Q08CL8, Q0VEJ0, Q14161, Q15650, Q3TLI0, Q4R350, Q5RAQ5, Q5RCP7, Q5RDV5, Q5TKA1, Q5XIA4, Q5ZIW2, Q5ZJK1, Q68CZ1, Q6AYF1, Q6QD73, Q7TSG1, Q7ZYH1, Q8BH15, Q8BIK4, Q8BKH7, Q8C735, Q8CG73, Q8CGF6, Q8IWR0, Q8IZQ1, Q8N6S4, Q8N960, Q8NEU8

Diamond homologs: A2VDU2, A4IIM3, Q5RDV5, Q6AYF1, Q6QD73, Q7ZYH1, Q8BKH7, Q9BPZ7, Q9P7Y9, Q9W6S3

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PIP3	“up-regulates activity”	MAPKAP1	“chemical activation”
MAPKAP1	“up-regulates activity”	PRKCE	binding
RPS6KB1	“down-regulates activity”	MAPKAP1	phosphorylation
AKT1	“up-regulates activity”	MAPKAP1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 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	8	67.7×	2e-11
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	8	59.7×	5e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	52.2×	2e-09
Activation of BH3-only proteins	8	44.1×	6e-10
RHO GTPases activate PKNs	8	28.2×	2e-08
Intrinsic Pathway for Apoptosis	8	26.0×	3e-08
Constitutive Signaling by AKT1 E17K in Cancer	5	23.5×	5e-05
FOXO-mediated transcription	6	22.4×	7e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	7	19.7×	7e-05
transcription initiation-coupled chromatin remodeling	5	14.7×	4e-03
phosphatidylinositol 3-kinase/protein kinase B signal transduction	8	13.0×	1e-04
G2/M transition of mitotic cell cycle	5	12.0×	9e-03
cellular response to insulin stimulus	7	9.2×	2e-03
positive regulation of cell growth	6	8.4×	9e-03
intracellular protein localization	9	7.2×	1e-03
protein phosphorylation	12	6.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	1
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

3334 predictions. Top by Δscore:

Variant	Effect	Δscore
9:125439655:T:TA	donor_gain	1.0000
9:125444596:GACCT:G	acceptor_loss	1.0000
9:125444597:ACC:A	acceptor_loss	1.0000
9:125444598:CCTGC:C	acceptor_loss	1.0000
9:125444599:CTGC:C	acceptor_loss	1.0000
9:125444600:T:A	acceptor_loss	1.0000
9:125467970:A:AC	donor_gain	1.0000
9:125467971:C:CC	donor_gain	1.0000
9:125467971:CTGG:C	donor_gain	1.0000
9:125467971:CTGGG:C	donor_gain	1.0000
9:125484442:CCTAG:C	donor_gain	1.0000
9:125506306:GT:G	donor_loss	1.0000
9:125506307:TAC:T	donor_loss	1.0000
9:125506308:A:AC	donor_gain	1.0000
9:125506308:A:C	donor_loss	1.0000
9:125506309:C:A	donor_loss	1.0000
9:125506309:C:CA	donor_gain	1.0000
9:125506309:CTGTT:C	donor_gain	1.0000
9:125506334:C:CA	donor_gain	1.0000
9:125559805:TGTCA:T	acceptor_gain	1.0000
9:125559806:GTCA:G	acceptor_gain	1.0000
9:125559807:TCA:T	acceptor_gain	1.0000
9:125559807:TCAC:T	acceptor_loss	1.0000
9:125559808:CA:C	acceptor_gain	1.0000
9:125559808:CAC:C	acceptor_gain	1.0000
9:125559809:AC:A	acceptor_loss	1.0000
9:125559810:C:CC	acceptor_gain	1.0000
9:125559811:T:C	acceptor_loss	1.0000
9:125585553:A:AC	donor_gain	1.0000
9:125585554:C:CT	donor_gain	1.0000

AlphaMissense

3450 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:125484445:A:G	L402P	1.000
9:125506324:A:G	L351P	1.000
9:125506330:A:G	F349S	1.000
9:125506402:A:G	L325P	1.000
9:125506402:A:T	L325Q	1.000
9:125543095:C:G	A308P	1.000
9:125559639:A:T	V281D	1.000
9:125559690:A:G	L264P	1.000
9:125559693:G:T	A263D	1.000
9:125559694:C:G	A263P	1.000
9:125559696:A:G	L262S	1.000
9:125559704:G:C	F259L	1.000
9:125559704:G:T	F259L	1.000
9:125559705:A:C	F259C	1.000
9:125559705:A:G	F259S	1.000
9:125559706:A:C	F259V	1.000
9:125559706:A:G	F259L	1.000
9:125559706:A:T	F259I	1.000
9:125559710:A:C	F257L	1.000
9:125559710:A:T	F257L	1.000
9:125559711:A:G	F257S	1.000
9:125559712:A:G	F257L	1.000
9:125559715:T:C	K256E	1.000
9:125559738:A:G	L248P	1.000
9:125559738:A:T	L248Q	1.000
9:125559746:G:C	F245L	1.000
9:125559746:G:T	F245L	1.000
9:125559747:A:C	F245C	1.000
9:125559747:A:G	F245S	1.000
9:125559748:A:C	F245V	1.000

dbSNP variants (sampled 300 via entrez): RS1000013872 (9:125442393 T>A,C), RS1000020186 (9:125457960 TC>T), RS1000026501 (9:125708906 G>A), RS1000026630 (9:125528563 G>A), RS1000055686 (9:125501174 G>A), RS1000058488 (9:125673201 A>G), RS1000073001 (9:125617903 C>G), RS1000105171 (9:125591328 G>A), RS1000114627 (9:125555874 T>C), RS1000125823 (9:125502831 T>C), RS1000129373 (9:125632345 C>A), RS1000135006 (9:125535056 T>C), RS1000136490 (9:125492433 T>G), RS1000139504 (9:125709146 A>G), RS1000146528 (9:125635638 ACT>A)

Disease associations

OMIM: gene MIM:610558 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST003818_1	Resting heart rate	1.000000e-15
GCST004861_96	Itch intensity from mosquito bite	2.000000e-06
GCST004862_11	Itch intensity from mosquito bite adjusted by bite size	8.000000e-06
GCST004862_193	Itch intensity from mosquito bite adjusted by bite size	4.000000e-07
GCST004862_194	Itch intensity from mosquito bite adjusted by bite size	5.000000e-06
GCST004865_43	Itch intensity from mosquito bite adjusted by bite size	1.000000e-07
GCST004904_48	Body mass index	6.000000e-07
GCST004904_64	Body mass index	6.000000e-10
GCST006479_19	Diverticular disease	8.000000e-06
GCST006914_12	Sleep duration	2.000000e-10
GCST007327_172	Smoking status (ever vs never smokers)	3.000000e-10
GCST007929_61	Medication use (calcium channel blockers)	1.000000e-08
GCST010138_5	Raw vegetable consumption	4.000000e-09
GCST010142_3	Fish- and plant-related diet	2.000000e-12
GCST010142_57	Fish- and plant-related diet	1.000000e-09
GCST90007003_11	Gut microbiota relative abundance (Ruminococcus belonging to family Lachnospiraceae)	2.000000e-06

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0008377	mosquito bite reaction itch intensity measurement
EFO:0008378	mosquito bite reaction size measurement
EFO:0004340	body mass index
EFO:0009959	diverticular disease
EFO:0004318	smoking behavior
EFO:0009930	Calcium channel blocker use measurement
EFO:0008111	diet measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): 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

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

ChEMBL bioactivities

125 potent at pChembl≥5 of 126 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 256 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

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	6
Benzo(a)pyrene	affects methylation, decreases expression	4
Cannabidiol	affects cotreatment, increases expression	3
Cisplatin	decreases expression	2
Aflatoxin B1	affects methylation, increases methylation	2
Particulate Matter	increases expression, increases abundance	2
FR900359	increases phosphorylation	1
moringin	affects cotreatment, increases expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
benzo(e)pyrene	decreases methylation	1
aflatoxin B2	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
bisphenol S	decreases methylation	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	decreases expression	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylstilbestrol	increases expression	1
Ethyl Methanesulfonate	increases expression	1

ChEMBL screening assays

93 unique, capped per target: 93 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4308949	Binding	Inhibition of recombinant mTORC2 (unknown origin) expressed in Escherichia coli after 15 mins in presence of gamma-[32]P-ATP by high-throughput screening assay	Design of Small Molecule Autophagy Modulators: A Promising Druggable Strategy. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SX02	HAP1 MAPKAP1 (-) 1	Cancer cell line	Male
CVCL_SX03	HAP1 MAPKAP1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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