RPS6KB2

Summary

RPS6KB2 (ribosomal protein S6 kinase B2, HGNC:10437) is a protein-coding gene on chromosome 11q13.2, encoding Ribosomal protein S6 kinase beta-2 (Q9UBS0). Phosphorylates specifically ribosomal protein S6.

This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation.

Source: NCBI Gene 6199 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 119 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003952

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:10437
Approved symbol	RPS6KB2
Name	ribosomal protein S6 kinase B2
Location	11q13.2
Locus type	gene with protein product
Status	Approved
Aliases	p70S6Kb, P70-BETA, STK14B, KLS, S6KB, S6Kbeta, S6Kβ
Ensembl gene	ENSG00000175634
Ensembl biotype	protein_coding
OMIM	608939
Entrez	6199

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 9 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000312629, ENST00000420069, ENST00000524814, ENST00000524934, ENST00000525088, ENST00000525726, ENST00000525996, ENST00000526268, ENST00000528964, ENST00000530623, ENST00000531765, ENST00000556575, ENST00000875116, ENST00000875117, ENST00000875118, ENST00000925337, ENST00000925338, ENST00000942409

RefSeq mRNA: 1 — MANE Select: NM_003952 NM_003952

CCDS: CCDS41677

Canonical transcript exons

ENST00000312629 — 15 exons

Exon	Start	End
ENSE00001337277	67434989	67435401
ENSE00003393918	67431368	67431515
ENSE00003473628	67429527	67429595
ENSE00003481813	67428494	67428623
ENSE00003488998	67428982	67429022
ENSE00003495386	67433126	67433216
ENSE00003505356	67434582	67434694
ENSE00003506159	67432600	67432657
ENSE00003527859	67432952	67433042
ENSE00003550598	67434198	67434275
ENSE00003588460	67432737	67432837
ENSE00003609959	67433995	67434057
ENSE00003621740	67433340	67433447
ENSE00003644702	67434377	67434484
ENSE00003668289	67429120	67429240

Expression profiles

Bgee: expression breadth ubiquitous, 219 present calls, max score 97.56.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.5253 / max 117.8145, expressed in 1819 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115465	23.5253	1819

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.56	gold quality
skin of leg	UBERON:0001511	97.30	gold quality
skin of abdomen	UBERON:0001416	97.13	gold quality
esophagus mucosa	UBERON:0002469	95.65	gold quality
granulocyte	CL:0000094	95.57	gold quality
body of stomach	UBERON:0001161	94.44	gold quality
apex of heart	UBERON:0002098	94.27	gold quality
right lobe of liver	UBERON:0001114	94.14	gold quality
esophagus	UBERON:0001043	93.90	gold quality
zone of skin	UBERON:0000014	93.85	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.76	gold quality
adenohypophysis	UBERON:0002196	93.69	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.54	gold quality
cerebellar hemisphere	UBERON:0002245	93.37	gold quality
mucosa of transverse colon	UBERON:0004991	93.32	gold quality
right lobe of thyroid gland	UBERON:0001119	93.31	gold quality
minor salivary gland	UBERON:0001830	93.21	gold quality
cerebellar cortex	UBERON:0002129	93.19	gold quality
ectocervix	UBERON:0012249	93.00	gold quality
left uterine tube	UBERON:0001303	92.99	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.81	gold quality
left lobe of thyroid gland	UBERON:0001120	92.76	gold quality
body of pancreas	UBERON:0001150	92.52	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	92.42	gold quality
lower esophagus	UBERON:0013473	92.35	gold quality
lower esophagus muscularis layer	UBERON:0035833	92.33	gold quality
left adrenal gland cortex	UBERON:0035825	92.29	gold quality
gastrocnemius	UBERON:0001388	92.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.25	gold quality
right adrenal gland	UBERON:0001233	92.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.07

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

2 targeting RPS6KB2, 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-4641	99.28	66.64	744
HSA-MIR-361-3P	99.19	66.45	1381

Literature-anchored findings (GeneRIF, showing 28)

• p70 S6 kinase regulates neutrophilic differentiation in HL-60 cells (PMID:12176053)
• regulation of nucleocytoplasmic shuttling of S6KbetaII by protein kinase C-mediated phosphorylation (PMID:12529391)
• the PI3K/p70 S6K/c-Myc cascade plays an important role in neutrophilic proliferation in HL-60 cells. (PMID:12818373)
• These data suggest that activated p70 S6 kinase could mediate an up-regulation of tau translation. (PMID:12875979)
• p70 ribosomal protein S6 kinase activity was induced by K-Ras in a phosphatidylinositol 3-kinase and mTOR-dependent manner. (PMID:14729629)
• IFNgamma-activated p70 S6 kinase phosphorylates the 40S S6 ribosomal protein on serines 235/236, to regulate IFNgamma-dependent mRNA translation. (PMID:15051500)
• S6K2 is active throughout the cell cycle with higher activity in G2 and M phases. (PMID:17786541)
• heterogeneous ribonucleoprotein F is involved in the regulation of cell proliferation via the mammalian target of rapamycin/S6 kinase 2 pathway (PMID:20308064)
• Dysregulation of S6 kinases contributes to the pathogenesis of human diseases. (PMID:20932932)
• S6K1 and S6K2 gene amplification was associated with a worse prognosis. (PMID:20953835)
• Data show that genetic variation in RPS6KA1, RPS6KA2, and PRS6KB2 were associated with risk of developing colon cancer while only genetic variation in RPS6KA2 was associated with altering risk of rectal cancer. (PMID:21035469)
• Study shows that the two homologues of S6K have distinct effects on Akt activation and cell survivalin breast cancer. (PMID:21427355)
• S6K2 expression dictates tissue-specific requirement for S6K1 in mediating aberrant mTORC1 signaling and tumorigenesis (PMID:21444676)
• The p85 S6K1 promotes H2O2-induced cell death via a rapamycin-insensitive mechanism. (PMID:22955948)
• S6K2 amplification was frequently observed in gastric cancer and was related to a poor prognosis (PMID:23393338)
• The mTOR effectors 4EBP1 and S6K2 are frequently coexpressed, and associated with a poor prognosis and endocrine resistance in breast cancer. (PMID:24131622)
• discovered that ERBB4 and S6K2 were the direct targets of miR-193a-3p and that PIK3R3 and mTOR were the direct targets of miR-193a-5p in non-small-cell lung cancer (PMID:24469061)
• Degradation of Tiam1 by casein kinase 1 and the SCFbetaTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling. (PMID:25124033)
• We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery. (PMID:27407113)
• p54-S6K2 interactome is predominant to the nucleus, whereas p70-S6K1 is predominant to cytosol. (PMID:27493124)
• Overexpression of catalytically-active Akt or knockdown of glycogen synthase kinase-3 (GSK3)-beta, a substrate for Akt, had little effect on Mcl-1 downregulation caused by S6K2 deficiency (PMID:28301598)
• The results suggest that although the polyproline region of S6K2 is capable of generating ribosomal stalling, the depletion of eIF5A in HeLa cells seems to be insufficient to cause an expressive decrease in the content of endogenous S6K2. (PMID:30320934)
• Role of S6K2 in cancer cell survival.[review] (PMID:30730779)
• Distinct Roles of mTOR Targets S6K1 and S6K2 in Breast Cancer. (PMID:32054043)
• Circ-GLI1 promotes metastasis in melanoma through interacting with p70S6K2 to activate Hedgehog/GLI1 and Wnt/beta-catenin pathways and upregulate Cyr61. (PMID:32732916)
• Activation of Mechanistic Target of Rapamycin (mTOR) in Human Endothelial Cells Infected with Pathogenic Spotted Fever Group Rickettsiae. (PMID:33003310)
• NSUN6, an RNA methyltransferase of 5-mC controls glioblastoma response to temozolomide (TMZ) via NELFB and RPS6KB2 interaction. (PMID:34705606)
• Ribosomal protein S6 kinase 2 (RPS6KB2) is a potential immunotherapeutic target for cancer that upregulates proinflammatory cytokines. (PMID:38281249)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
mus_musculus	Rps6kb2	ENSMUSG00000024830
rattus_norvegicus	Rps6kb2	ENSRNOG00000021689
drosophila_melanogaster	JIL-1	FBGN0020412
drosophila_melanogaster	S6k	FBGN0283472
caenorhabditis_elegans	rskn-2	WBGENE00008311
caenorhabditis_elegans		WBGENE00012929
caenorhabditis_elegans		WBGENE00017898
caenorhabditis_elegans		WBGENE00044281

Paralogs (7): RPS6KA2 (ENSG00000071242), RPS6KA6 (ENSG00000072133), RPS6KA5 (ENSG00000100784), RPS6KB1 (ENSG00000108443), RPS6KA1 (ENSG00000117676), RPS6KA4 (ENSG00000162302), RPS6KA3 (ENSG00000177189)

Protein

Protein identifiers

Ribosomal protein S6 kinase beta-2 — Q9UBS0 (reviewed: Q9UBS0)

Alternative names: 70 kDa ribosomal protein S6 kinase 2, S6 kinase-related kinase, Serine/threonine-protein kinase 14B, p70 ribosomal S6 kinase beta

All UniProt accessions (5): Q9UBS0, E9PIP7, E9PQF6, G3V2F1, R4GN47

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates specifically ribosomal protein S6. Seems to act downstream of mTOR signaling in response to growth factors and nutrients to promote cell proliferation, cell growth and cell cycle progression in an alternative pathway regulated by MEAK7.

Subcellular location. Cytoplasm. Nucleus.

Post-translational modifications. Phosphorylated and activated by MTOR. Phosphorylation by PKC within the NLS in response to mitogenic stimuli causes cytoplasmic retention.

Similarity. Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. S6 kinase subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9UBS0-1	1	yes
Q9UBS0-2	2

RefSeq proteins (1): NP_003943* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000961	AGC-kinase_C	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016238	Ribosomal_S6_kinase	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR017892	Pkinase_C	Domain

Pfam: PF00069, PF00433

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (24 total): modified residue 4, sequence variant 4, compositionally biased region 3, domain 2, binding site 2, splice variant 2, sequence conflict 2, region of interest 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBS0-F1	76.22	0.49

Functional residue map

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

Catalytic / active sites (1): 194 (proton acceptor)

Ligand- & substrate-binding residues (2): 73–81; 99

Post-translational modifications (4): 15, 417, 423, 473

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-198693	AKT phosphorylates targets in the nucleus
R-HSA-5674400	Constitutive Signaling by AKT1 E17K in Cancer
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-2219528	PI3K/AKT Signaling in Cancer
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 210 (showing top): MORF_RAGE, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, MORF_ATRX, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_TRANSLATIONAL_INITIATION, MORF_ESR1, GGGTGGRR_PAX4_03, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, chr11q13, GOBP_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_TRANSLATION, GOBP_POSITIVE_REGULATION_OF_TRANSLATIONAL_INITIATION, GOBP_POST_TRANSCRIPTIONAL_REGULATION_OF_GENE_EXPRESSION

GO Biological Process (8): translation (GO:0006412), signal transduction (GO:0007165), TOR signaling (GO:0031929), TORC1 signaling (GO:0038202), positive regulation of translational initiation (GO:0045948), negative regulation of insulin receptor signaling pathway (GO:0046627), cytoplasmic translation (GO:0002181), protein phosphorylation (GO:0006468)

GO Molecular Function (9): protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), ribosomal protein S6 kinase activity (GO:0004711), ATP binding (GO:0005524), peptide binding (GO:0042277), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nucleus (GO:0005634)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
PIP3 activates AKT signaling	1
PI3K/AKT Signaling in Cancer	1
Intracellular signaling by second messengers	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Disease	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
translational initiation	2
protein kinase activity	2
cellular anatomical structure	2
peptidyltransferase activity	1
translational elongation	1
translational termination	1
macromolecule biosynthetic process	1
protein metabolic process	1
protein biosynthetic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signal transduction	1
TOR signaling	1
regulation of translational initiation	1
positive regulation of translation	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
translation	1
phosphorylation	1
protein modification process	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
protein serine/threonine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
nuclear lumen	1
intracellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3108 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
RPS6KB2	RPTOR	Q8N122	927
RPS6KB2	RPS6	P08227	917
RPS6KB2	EIF4E	P06730	904
RPS6KB2	RHEB	Q15382	894
RPS6KB2	NCOR1	O75376	894
RPS6KB2	MTOR	P42345	894
RPS6KB2	TSC2	P49815	878
RPS6KB2	IRS1	P35568	864
RPS6KB2	TSC1	Q92574	858
RPS6KB2	EIF4EBP1	Q13541	836
RPS6KB2	BRAF	P15056	826
RPS6KB2	POLDIP3	Q9BY77	794
RPS6KB2	TPT1	P13693	786
RPS6KB2	RICTOR	Q6R327	769
RPS6KB2	PPP1R9A	Q9ULJ8	748

IntAct

23 interactions, top by confidence:

A	B	Type	Score
CSNK2B	RPS6KB2	psi-mi:“MI:0915”(physical association)	0.590
CSNK2B	RPS6KB2	psi-mi:“MI:0403”(colocalization)	0.590
RPS6KB2	CSNK2B	psi-mi:“MI:0914”(association)	0.590
RPS6KB2	LRRK2	psi-mi:“MI:0407”(direct interaction)	0.440
RPS6KB2	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RPS6	RPS6KB2	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RPS6KB2	CCDC47	psi-mi:“MI:0915”(physical association)	0.400
COASY	RPS6KB2	psi-mi:“MI:0915”(physical association)	0.400
RPS6KB2	ATP5F1A	psi-mi:“MI:0915”(physical association)	0.370
CFTR	RPS6KB2	psi-mi:“MI:0915”(physical association)	0.370
RPS6KB2	MAPK8IP2	psi-mi:“MI:0915”(physical association)	0.370
JUN	TPM3	psi-mi:“MI:0914”(association)	0.350
RPS6KB2	BRAF	psi-mi:“MI:0914”(association)	0.350
RPS6KB2	ACACB	psi-mi:“MI:0914”(association)	0.350
RPS6KB2	SRSF1	psi-mi:“MI:0914”(association)	0.350
RPS6KB2	HSP90AA1	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
SPAST	PLXNB2	psi-mi:“MI:0914”(association)	0.350
SNW1		psi-mi:“MI:0914”(association)	0.350
CDC5L		psi-mi:“MI:0914”(association)	0.350
EEF2K	RPS6KB2	psi-mi:“MI:0217”(phosphorylation reaction)	0.310

BioGRID (298): RPS6KB2 (Affinity Capture-RNA), RPS6KB2 (Affinity Capture-RNA), ACPP (Affinity Capture-MS), ACTA1 (Affinity Capture-MS), ACTG1 (Affinity Capture-MS), AIFM1 (Affinity Capture-MS), ALB (Affinity Capture-MS), ALG1 (Affinity Capture-MS), ANKMY2 (Affinity Capture-MS), ANXA2 (Affinity Capture-MS), ATP1A1 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), BRAF (Affinity Capture-MS), RTCB (Affinity Capture-MS)

ESM2 similar proteins: A5PKJ4, B2DD29, B8Y466, O14976, O43781, O54781, O60307, O70551, O88831, P0C865, P33279, P78362, P97756, Q13164, Q20443, Q3U214, Q3V016, Q4R6S5, Q4R8E0, Q4V793, Q4V8A3, Q5RD27, Q5RJI5, Q641K5, Q84M93, Q86UX6, Q8C078, Q8CIP4, Q8N5S9, Q8NE63, Q8QZV4, Q8TD08, Q8TDC3, Q8VBY2, Q8WP28, Q922Y0, Q96L34, Q96RR4, Q96SB4, Q99KY4

Diamond homologs: A0A7J6K7I9, A0A7J6K7Y0, A0A7J6KD88, A8X775, B1WAR9, C4YRB7, D2HXI8, E1C2I2, E9PSL7, G1X456, G5EGQ3, M3TYT0, O00506, O01583, O01700, O14578, O54874, O61267, O75116, O77819, O80902, O88643, O97627, P05131, P0CY23, P0CY24, P13677, P21146, P25098, P26817, P26818, P32865, P34100, P35465, P38070, P48562, P49025, P49673, P54265, P70335

SIGNOR signaling

23 interactions.

A	Effect	B	Mechanism
PDPK1	up-regulates	RPS6KB2	phosphorylation
SRC	unknown	RPS6KB2	phosphorylation
MTOR	up-regulates	RPS6KB2	phosphorylation
RPS6KB2	down-regulates	PDCD4	phosphorylation
RPS6KB2	down-regulates	MXD1	phosphorylation
mTORC1	up-regulates	RPS6KB2	phosphorylation
RPS6KB2	“up-regulates activity”	HNRNPA1	phosphorylation
TSC2	down-regulates	RPS6KB2
PRKCA	unknown	RPS6KB2	phosphorylation
PRKCB	unknown	RPS6KB2	phosphorylation
PRKCD	unknown	RPS6KB2	phosphorylation
PRKCE	unknown	RPS6KB2	phosphorylation
PRKCG	unknown	RPS6KB2	phosphorylation
PDPK1	“up-regulates activity”	RPS6KB2	phosphorylation
MTOR	“up-regulates activity”	RPS6KB2	phosphorylation
RPS6KB2	“up-regulates activity”	TARBP2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	87
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1661 predictions. Top by Δscore:

Variant	Effect	Δscore
11:67429115:CGTA:C	acceptor_loss	1.0000
11:67429116:GTAG:G	acceptor_loss	1.0000
11:67429117:TA:T	acceptor_loss	1.0000
11:67429118:A:AG	acceptor_gain	1.0000
11:67429118:A:C	acceptor_loss	1.0000
11:67429119:G:GA	acceptor_loss	1.0000
11:67429119:G:GG	acceptor_gain	1.0000
11:67429119:GGC:G	acceptor_gain	1.0000
11:67429119:GGCCT:G	acceptor_gain	1.0000
11:67429208:C:G	donor_gain	1.0000
11:67429237:CAAG:C	donor_loss	1.0000
11:67429241:GTAG:G	donor_loss	1.0000
11:67429242:T:A	donor_loss	1.0000
11:67431362:CTCCA:C	acceptor_loss	1.0000
11:67431364:CCA:C	acceptor_loss	1.0000
11:67431365:CAGGC:C	acceptor_loss	1.0000
11:67431366:A:AC	acceptor_loss	1.0000
11:67431366:A:AG	acceptor_gain	1.0000
11:67431367:G:GC	acceptor_loss	1.0000
11:67431367:G:GG	acceptor_gain	1.0000
11:67431367:GGCCA:G	acceptor_gain	1.0000
11:67431482:G:GA	donor_gain	1.0000
11:67431501:T:TG	donor_gain	1.0000
11:67431513:GTG:G	donor_gain	1.0000
11:67431515:GGTA:G	donor_gain	1.0000
11:67432732:TGCA:T	acceptor_loss	1.0000
11:67432733:GCA:G	acceptor_loss	1.0000
11:67432734:CAGCT:C	acceptor_loss	1.0000
11:67432735:A:AG	acceptor_gain	1.0000
11:67432735:AGC:A	acceptor_loss	1.0000

AlphaMissense

3141 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:67432802:A:C	D194A	1.000
11:67432802:A:G	D194G	1.000
11:67432802:A:T	D194V	1.000
11:67432970:A:T	D212V	1.000
11:67433027:G:A	G231D	1.000
11:67429583:A:C	K99N	0.999
11:67429583:A:T	K99N	0.999
11:67429595:G:C	K103N	0.999
11:67429595:G:T	K103N	0.999
11:67431417:G:C	R120P	0.999
11:67431495:T:C	L146P	0.999
11:67432799:G:C	R193P	0.999
11:67432803:C:A	D194E	0.999
11:67432803:C:G	D194E	0.999
11:67432805:T:A	L195H	0.999
11:67432805:T:C	L195P	0.999
11:67432807:A:G	K196E	0.999
11:67432809:G:C	K196N	0.999
11:67432809:G:T	K196N	0.999
11:67432818:C:A	N199K	0.999
11:67432818:C:G	N199K	0.999
11:67432969:G:C	D212H	0.999
11:67432970:A:C	D212A	0.999
11:67432971:C:A	D212E	0.999
11:67432971:C:G	D212E	0.999
11:67432986:G:C	K217N	0.999
11:67432986:G:T	K217N	0.999
11:67433018:C:T	T228I	0.999
11:67433024:G:A	C230Y	0.999
11:67433026:G:C	G231R	0.999

dbSNP variants (sampled 300 via entrez): RS1000277298 (11:67430285 T>G), RS1000306398 (11:67435820 ACTCAGCAGGGC>A), RS1000628032 (11:67430721 A>G), RS1000965868 (11:67434507 T>C,G), RS1001017837 (11:67427379 G>C), RS1001142570 (11:67427706 GT>G,GTT), RS1001400569 (11:67430883 T>C), RS1002398046 (11:67429463 G>C), RS1002426414 (11:67427933 G>A,T), RS1002458131 (11:67434933 T>C), RS1004877931 (11:67429575 G>A), RS1005127064 (11:67434779 G>A,C,T), RS1005217839 (11:67426501 C>T), RS1006387197 (11:67431139 T>C), RS1006549519 (11:67431620 T>C)

Disease associations

OMIM: gene MIM:608939 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST010002_241	Refractive error	3.000000e-13
GCST90002390_36	Mean corpuscular hemoglobin	5.000000e-10
GCST90002392_351	Mean corpuscular volume	7.000000e-29
GCST90002397_531	Mean spheric corpuscular volume	5.000000e-38
GCST90020028_1919	Hip circumference adjusted for BMI	3.000000e-08
GCST90020029_346	Waist circumference adjusted for body mass index	5.000000e-12

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0008039	BMI-adjusted hip circumference
EFO:0007789	BMI-adjusted waist circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111330 (PROTEIN COMPLEX), CHEMBL3111 (SINGLE PROTEIN), CHEMBL3832633 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 779 (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
CHEMBL3544960	AT-13148	1	779

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — p70 subfamily

ChEMBL bioactivities

30 potent at pChembl≥5 of 34 total, top 30 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.14	IC50	0.726	nM	STAUROSPORINE
8.82	IC50	1.51	nM	STAUROSPORINE
8.63	IC50	2.35	nM	STAUROSPORINE
8.42	IC50	3.79	nM	CHEMBL3909070
8.35	IC50	4.48	nM	CHEMBL5570033
8.12	IC50	7.58	nM	CHEMBL3927587
7.99	IC50	10.3	nM	CHEMBL3924878
7.92	IC50	12	nM	AT-13148
7.90	IC50	12.7	nM	CHEMBL3911801
7.74	IC50	18.2	nM	CHEMBL5571683
7.53	IC50	29.4	nM	CHEMBL3889534
7.40	IC50	40	nM	CHEMBL426445
7.17	IC50	66.82	nM	CHEMBL5423601
7.00	Ki	100	nM	CHEMBL4249925
6.19	IC50	640	nM	CHEMBL192909
6.09	IC50	820	nM	CHEMBL190057
6.08	IC50	834.9	nM	CHEMBL5401267
6.06	IC50	870	nM	CHEMBL366201
6.02	IC50	950	nM	CHEMBL193232
6.00	IC50	1000	nM	CHEMBL253116
5.94	IC50	1140	nM	CHEMBL193172
5.89	IC50	1280	nM	CHEMBL193162
5.87	IC50	1360	nM	CHEMBL364499
5.78	IC50	1650	nM	CHEMBL5094006
5.58	IC50	2620	nM	CHEMBL437331
5.47	Ki	3400	nM	CHEMBL210618
5.21	IC50	6130	nM	CHEMBL190143
5.02	IC50	9610	nM	CHEMBL190039
5.00	IC50	1e+04	nM	CHEMBL366185
5.00	IC50	1e+04	nM	CHEMBL215205

PubChem BioAssay actives

24 with measured affinity, of 253 total; 22 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
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1715232: Inhibition of human p70S6Kb using KKRNRTLTK as substrate by [gamma-33P]-ATP assay	ic50	0.0007	uM
N-(6-chloro-3-nitro-2-pyridinyl)-6-(3,5-dimethoxyphenyl)quinazolin-2-amine	2105178: Inhibition of human wild type S6K2 using RBER-CHKtide as substrate in presence of ATP by hotspot assay	ic50	0.0045	uM
N-(6-chloro-3-nitro-2-pyridinyl)-6-(2,6-dichloro-3,5-dimethoxyphenyl)quinazolin-2-amine	2105178: Inhibition of human wild type S6K2 using RBER-CHKtide as substrate in presence of ATP by hotspot assay	ic50	0.0182	uM
2,3-dithiophen-2-ylbenzo[g]quinoxaline-7-carboxylic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	0.0400	uM
N-[3-cyclopropyl-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-5-methyl-18-oxo-9-oxa-17,23,25,26-tetrazatetracyclo[17.5.2.14,8.022,25]heptacosa-1(24),4,6,8(27),19(26),20,22-heptaen-2-yne-6-carboxamide	2014053: Inhibition of P70S6K (unknown origin)	ic50	0.0668	uM
2-[3-(methanesulfonamido)phenyl]-N-[4-(1H-pyrrolo[2,3-b]pyridin-3-yl)-1,3-thiazol-2-yl]acetamide	1398932: Inhibition of p70S6K (unknown origin)	ki	0.1000	uM
2-[5-[3-[4-(carboxymethyl)thiophen-2-yl]benzo[g]quinoxalin-2-yl]thiophen-3-yl]acetic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	0.6400	uM
4-[5-[3-[5-(3-carboxypropyl)thiophen-2-yl]benzo[g]quinoxalin-2-yl]thiophen-2-yl]butanoic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	0.8200	uM
4-N-(3-aminopropyl)-2-N-(2-methylsulfonyl-3,4-dihydro-1H-isoquinolin-6-yl)-5-(trifluoromethyl)pyrimidine-2,4-diamine	2026722: Inhibition of p70S6K (unknown origin) using peptide substrate incubated for 1 hrs in presence of ATP by fluorescence microplate reader	ic50	0.8348	uM
3-[5-[3-[5-(2-carboxyethyl)thiophen-2-yl]benzo[g]quinoxalin-2-yl]thiophen-2-yl]propanoic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	0.8700	uM
7,8-dithiophen-2-yl-2,3-dihydro-[1,4]dioxino[2,3-g]quinoxaline-3-carboxylic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	0.9500	uM
5-(4-anilinoanilino)-N’-(1-hydroxypropan-2-yl)-3-oxo-1,2-thiazole-4-carboximidamide	273735: Inhibition of p70 S6 kinase	ic50	1.0000	uM
7,8-dimethoxy-2,3-dithiophen-2-ylpyrazino[2,3-b]quinoxaline	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	1.1400	uM
2-[5-[3-[5-(carboxymethyl)thiophen-2-yl]benzo[g]quinoxalin-2-yl]thiophen-2-yl]acetic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	1.2800	uM
2,3-dithiophen-2-ylbenzo[g]quinoxaline	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	1.3600	uM
N-(2,6-diethylphenyl)-2-[4-(4-methylpiperazin-1-yl)-2-(prop-2-enoylamino)anilino]-5,6-dihydropyrimido[4,5-e]indolizine-7-carboxamide	1819637: Inhibition of human recombinant P70S6Kbeta expressed in Sf9 insect cells using [KKRNRTLTK] as substrate in presence of [33P]-ATP by radiometric hotspot kinetic assay	ic50	1.6500	uM
N’-(1-hydroxypropan-2-yl)-3-oxo-5-(4-phenoxyanilino)-1,2-thiazole-4-carboximidamide	273735: Inhibition of p70 S6 kinase	ic50	2.6200	uM
N-(4-amino-5-cyano-6-ethoxy-2-pyridinyl)-2-(2,5-dimethoxyphenyl)acetamide	266118: Inhibition of P70S6K	ki	3.4000	uM
methyl 3-[5-[3-[5-(3-methoxy-3-oxopropyl)thiophen-2-yl]benzo[g]quinoxalin-2-yl]thiophen-2-yl]propanoate	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	6.1300	uM
2,3-dithiophen-2-ylquinoxaline-6,7-diol	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	9.6100	uM
4-[(3,5-diamino-1H-pyrazol-4-yl)diazenyl]phenol	272483: Inhibition of P70S6K	ic50	10.0000	uM
5-[3-(5-carboxythiophen-2-yl)benzo[g]quinoxalin-2-yl]thiophene-2-carboxylic acid	242021: In vitro inhibition of SR protein kinase 1 by compound dissolved in 100% DMSO using 5’’-[gamma-33P]-triphosphate	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects methylation, increases expression	3
1-Butanol	decreases activity, affects cotreatment, increases abundance, increases expression	2
FR900359	decreases phosphorylation	1
moringin	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
beta-lapachone	increases expression	1
nickel sulfate	increases expression	1
coumarin	decreases phosphorylation	1
4-aminophenylarsenoxide	affects binding, decreases reaction	1
leptomycin B	decreases activity	1
myricetin	increases expression	1
ICG 001	increases expression	1
abrine	increases expression	1
Wortmannin	decreases reaction, increases activity	1
Temozolomide	decreases expression	1
Arsenic Trioxide	decreases reaction, affects binding	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cannabidiol	affects cotreatment, increases expression	1
Chelating Agents	affects binding, decreases expression	1
Copper	decreases expression, affects binding	1
Gasoline	increases expression, affects cotreatment, increases abundance	1
Ivermectin	decreases expression	1
Phosphatidic Acids	affects reaction, increases activity, decreases reaction	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Sodium Selenite	increases expression	1

ChEMBL screening assays

142 unique, capped per target: 141 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL803651	Binding	Inhibition of p70S6K in presence of 10 uM ATP	5-aryl-pyrazolo[3,4-b]pyridines: potent inhibitors of glycogen synthase kinase-3 (GSK-3). — Bioorg Med Chem Lett
CHEMBL4424897	ADMET	Inhibition of human full-length N-terminal His-tagged p70S6K expressed in baculovirus infected Sf21 insect cells using CKRRRLASLR as substrate	Optimization of an azetidine series as inhibitors of colony stimulating factor-1 receptor (CSF-1R) Type II to lead to the clinical candidate JTE-952. — Bioorg Med Chem Lett

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1YT	Abcam A-549 RPS6KB2 KO	Cancer cell line	Male
CVCL_D2CV	Abcam HCT 116 RPS6KB2 KO	Cancer cell line	Male
CVCL_D9R1	Ubigene HEK293 RPS6KB2 KO	Transformed cell line	Female
CVCL_TJ70	HAP1 RPS6KB2 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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