PIK3C2B

Summary

PIK3C2B (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta, HGNC:8972) is a protein-coding gene on chromosome 1q32.1, encoding Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta (O00750). Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns.

The protein encoded by this gene belongs to the phosphoinositide 3-kinase (PI3K) family. PI3-kinases play roles in signaling pathways involved in cell proliferation, oncogenic transformation, cell survival, cell migration, and intracellular protein trafficking. This protein contains a lipid kinase catalytic domain as well as a C-terminal C2 domain, a characteristic of class II PI3-kinases. C2 domains act as calcium-dependent phospholipid binding motifs that mediate translocation of proteins to membranes, and may also mediate protein-protein interactions. The PI3-kinase activity of this protein is sensitive to low nanomolar levels of the inhibitor wortmanin. The C2 domain of this protein was shown to bind phospholipids but not Ca2+, which suggests that this enzyme may function in a calcium-independent manner.

Source: NCBI Gene 5287 — RefSeq curated summary.

At a glance

• Gene–disease (curated): familial partial epilepsy (Moderate, GenCC)
• GWAS associations: 13
• Clinical variants (ClinVar): 307 total
• Druggable target: yes — 16 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001377334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8972
Approved symbol	PIK3C2B
Name	phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta
Location	1q32.1
Locus type	gene with protein product
Status	Approved
Aliases	C2-PI3K, PI3K-C2beta
Ensembl gene	ENSG00000133056
Ensembl biotype	protein_coding
OMIM	602838
Entrez	5287

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 6 protein_coding, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay, 1 retained_intron

ENST00000367184, ENST00000367187, ENST00000415899, ENST00000424712, ENST00000429009, ENST00000462752, ENST00000479079, ENST00000496872, ENST00000683234, ENST00000684373, ENST00000920831

RefSeq mRNA: 3 — MANE Select: NM_001377334 NM_001377334, NM_001377335, NM_002646

CCDS: CCDS1446, CCDS91148

Canonical transcript exons

ENST00000684373 — 33 exons

Exon	Start	End
ENSE00001039874	204429921	204430038
ENSE00001039875	204432200	204432401
ENSE00001039876	204428139	204428220
ENSE00001039877	204443417	204443597
ENSE00001039879	204440192	204440321
ENSE00001039880	204427648	204427754
ENSE00001039881	204447436	204447578
ENSE00001039882	204438935	204439071
ENSE00001039883	204449850	204450017
ENSE00001039885	204434439	204434608
ENSE00001039887	204449185	204449296
ENSE00001039889	204425613	204425741
ENSE00001039890	204433316	204433425
ENSE00001039892	204444331	204444424
ENSE00001039894	204433793	204433949
ENSE00001039895	204444068	204444162
ENSE00001039897	204441471	204441563
ENSE00001039905	204442526	204442633
ENSE00001039906	204445956	204446144
ENSE00001039907	204431669	204431793
ENSE00001075022	204454669	204454791
ENSE00001614036	204494356	204494805
ENSE00002208042	204465219	204465319
ENSE00002270559	204468870	204469886
ENSE00002348198	204460550	204460661
ENSE00002365436	204464012	204464132
ENSE00002376006	204455856	204456051
ENSE00002376668	204457037	204457070
ENSE00002407335	204457728	204457874
ENSE00002409527	204460324	204460403
ENSE00002425488	204459878	204459941
ENSE00002684661	204464450	204464604
ENSE00003918488	204422633	204425040

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 95.85.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 11.7471 / max 149.8239, expressed in 1416 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16940	6.4395	1253
16939	1.7970	744
16937	1.1139	631
16938	0.6955	443
16934	0.4802	261
16935	0.3246	179
16933	0.2808	143
16932	0.2735	126
16936	0.1424	59
16941	0.0927	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pancreatic ductal cell	CL:0002079	95.85	silver quality
inferior vagus X ganglion	UBERON:0005363	95.60	gold quality
gingival epithelium	UBERON:0001949	95.07	gold quality
pylorus	UBERON:0001166	94.97	gold quality
nipple	UBERON:0002030	94.74	gold quality
vena cava	UBERON:0004087	94.07	gold quality
ventral tegmental area	UBERON:0002691	94.03	gold quality
epithelium of nasopharynx	UBERON:0001951	94.02	gold quality
visceral pleura	UBERON:0002401	94.02	gold quality
superficial temporal artery	UBERON:0001614	93.98	gold quality
gingiva	UBERON:0001828	93.84	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.81	gold quality
subthalamic nucleus	UBERON:0001906	93.71	gold quality
thymus	UBERON:0002370	93.67	gold quality
pharyngeal mucosa	UBERON:0000355	93.65	gold quality
colonic mucosa	UBERON:0000317	93.64	gold quality
superior surface of tongue	UBERON:0007371	93.30	gold quality
corpus callosum	UBERON:0002336	93.29	gold quality
penis	UBERON:0000989	93.27	gold quality
cardia of stomach	UBERON:0001162	93.04	gold quality
inferior olivary complex	UBERON:0002127	92.95	gold quality
body of tongue	UBERON:0011876	92.74	gold quality
mammalian vulva	UBERON:0000997	92.50	gold quality
medulla oblongata	UBERON:0001896	92.38	gold quality
superior vestibular nucleus	UBERON:0007227	92.31	gold quality
tongue	UBERON:0001723	92.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	92.17	gold quality
upper arm skin	UBERON:0004263	91.84	gold quality
jejunum	UBERON:0002115	91.81	gold quality
squamous epithelium	UBERON:0006914	91.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.97

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

139 targeting PIK3C2B, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-153-5P	99.89	73.86	6317

Literature-anchored findings (GeneRIF, showing 20)

• different human small cell lung carcinoma cell lines overexpress distinct subsets of PI3Ks, resulting in differences in signalling cascades activated by stem cell factor; insights into specificity and functional significance of PI3K signalling in cancer (PMID:12356726)
• activity of nuclear phosphoinositide 3-kinase C2beta investigated in HL-60 cells induced to differentiate along granulocytic or monocytic lineages (PMID:12372612)
• plays a regulatory role in cell motility (PMID:16113997)
• identified the 185-kDa protein altered by nitrotyrosylation in platelets from patients with systemic sclerosis as phosphoinositide kinase C2beta (PI 3-K); the activity of PI 3-K increases in nitrotyrosylated platelet lystaes from patients with SSc (PMID:16271833)
• Class II phosphoinositide 3-kinase C2beta isnot essential for epidermal differentiation (PMID:16314532)
• These findings suggest that PI3KC2beta regulates the migration and survival of human tumor cells by distinct molecular mechanisms. (PMID:16775008)
• Epidermal growth factor stimulates the appearance of PI3K-C2beta in nuclei. (PMID:19496756)
• Data show that the class II phosphatidylinositol 3 kinase C2beta (PI3K-C2beta) is activated by the T-cell receptor (TCR) and functions upstream of NDPK-B to activate KCa3.1 channel activity. (PMID:19587117)
• Overexpression of PIK3C2B is associated with esophageal squamous cell carcinoma. (PMID:21986133)
• These findings provide a unique mechanism for regulating class II PI3Ks, and identify TRIM27 as a previously undescribed negative regulator of CD4 T cells. (PMID:22128329)
• The results of this study showed that strong association between PIK3C2B gene alternation and high-grade oligodendroglial tumors. (PMID:22825724)
• Data suggest a novel role for nucleotide-free Ras in cell signaling in which PI3KC2beta stabilizes nucleotide-free Ras and that interaction of Ras and PI3KC2beta mutually inhibit one another. (PMID:23028960)
• Class II enzyme PI3K-C2beta and the class IB isozyme p110gamma mainly regulate the S1P- and high density lipoprotein (HDL)-dependent endothelial cell (EC) migration and PI3K-C2alpha primarily controls EC survival (PMID:23320105)
• PI3KC2B-silencing inhibits early stages of neuroblastoa tumorigenic growth. (PMID:25622909)
• this study suggests that PIK3C2B might only have a minor role in SQCC oncogenesis (PMID:29088297)
• PI3K-C2alpha and PI3K-C2beta play differential, indispensable roles in clathrin-mediated pinocytosis. (PMID:30374841)
• Data reveal a novel role for the class II PI3K PI3K-C2beta during mitosis progression. (PMID:31752944)
• Higher PIK3C2B gene expression of H1N1+ specific B-cells is associated with lower H1N1 immunogenicity after trivalent influenza vaccination in HIV infected children. (PMID:32330555)
• The molecular mechanisms mediating class II PI 3-kinase function in cell physiology. (PMID:33387369)
• Defective lipid signalling caused by mutations in PIK3C2B underlies focal epilepsy. (PMID:35786744)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3c2b	ENSDARG00000086927
mus_musculus	Pik3c2b	ENSMUSG00000026447
rattus_norvegicus	Pik3c2b	ENSRNOG00000029938
drosophila_melanogaster	Pi3K68D	FBGN0015278
drosophila_melanogaster	Pi3K92E	FBGN0015279
caenorhabditis_elegans		WBGENE00000090
caenorhabditis_elegans		WBGENE00009552

Paralogs (9): PIK3C2A (ENSG00000011405), PIK3CB (ENSG00000051382), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3CA (ENSG00000121879), PIK3C2G (ENSG00000139144), PI4KB (ENSG00000143393), PIK3CD (ENSG00000171608), PI4KA (ENSG00000241973)

Protein

Protein identifiers

Phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta — O00750 (reviewed: O00750)

Alternative names: C2-PI3K, Phosphoinositide 3-kinase-C2-beta

All UniProt accessions (6): A2RUF7, F5GWN5, O00750, Q5SW97, Q5SW98, Q5SWA0

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates PtdIns and PtdIns4P with a preference for PtdIns. Does not phosphorylate PtdIns(4,5)P2. May be involved in EGF and PDGF signaling cascades.

Subunit / interactions. Part of a complex with ERBB2 and EGFR. Part of a complex with phosphorylated EGFR and GRB2. Interacts with phosphorylated EGFR and PDGFR, maybe indirectly. Interacts with GRB2.

Subcellular location. Microsome. Cell membrane. Cytoplasm. Cytosol. Nucleus. Endoplasmic reticulum.

Tissue specificity. Expressed in columnar and transitional epithelia, mononuclear cells, and ganglion cells (at protein level). Widely expressed, with highest levels in thymus and placenta and lowest in peripheral blood, skeletal muscle and kidney.

Activity regulation. Activated by GRB2.

Similarity. Belongs to the PI3/PI4-kinase family.

RefSeq proteins (3): NP_001364263, NP_001364264, NP_002637 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000341	PI3K_Ras-bd_dom	Domain
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR001263	PI3K_accessory_dom	Domain
IPR001683	PX_dom	Domain
IPR002420	PI3K-type_C2_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015433	PI3/4_kinase	Family
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR029071	Ubiquitin-like_domsf	Homologous_superfamily
IPR035892	C2_domain_sf	Homologous_superfamily
IPR036871	PX_dom_sf	Homologous_superfamily
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR042134	PX_PI3K_C2_beta	Domain
IPR042236	PI3K_accessory_sf	Homologous_superfamily

Pfam: PF00168, PF00454, PF00613, PF00787, PF00792, PF00794

Enzyme classification (BRENDA):

• EC 2.7.1.137 — phosphatidylinositol 3-kinase (BRENDA: 29 organisms, 131 substrates, 146 inhibitors, 16 Km, 0 kcat entries)
• EC 2.7.1.154 — phosphatidylinositol-4-phosphate 3-kinase (BRENDA: 7 organisms, 22 substrates, 53 inhibitors, 8 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.03–44	7
ATP	0.015–0.12	5
PHOSPHATIDYLINOSITOL	0.034–64	3
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.004–15	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.009–10	2
PHOSPHATIDYLINOSITOL	0.064–0.122	2
1,2-DIOCTANOYLPHOSPHATIDYLINOSITOL 4,5-DIPHOSPHA	0.05	1
PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE	0.011	1
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.025	1

Catalyzed reactions (Rhea), 2 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3-phosphate) + ADP + H(+) (RHEA:12709)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4-bisphosphate) + ADP + H(+) (RHEA:18373)

UniProt features (24 total): sequence conflict 8, domain 6, region of interest 6, compositionally biased region 3, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00750-F1	75.07	0.39

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane

MSigDB gene sets: 225 (showing top): AGGAAGC_MIR5163P, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VACUOLE_ORGANIZATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, SARRIO_EPITHELIAL_MESENCHYMAL_TRANSITION_DN, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_3_PHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_MACROAUTOPHAGY, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION

GO Biological Process (9): cellular response to starvation (GO:0009267), cell migration (GO:0016477), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), phosphatidylinositol-mediated signaling (GO:0048015), autophagosome organization (GO:1905037), lipid metabolic process (GO:0006629), macroautophagy (GO:0016236), phosphatidylinositol phosphate biosynthetic process (GO:0046854)

GO Molecular Function (9): ATP binding (GO:0005524), 1-phosphatidylinositol-3-kinase activity (GO:0016303), 1-phosphatidylinositol-4-phosphate 3-kinase activity (GO:0035005), phosphatidylinositol binding (GO:0035091), nucleotide binding (GO:0000166), lipid kinase activity (GO:0001727), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (10): nucleoplasm (GO:0005654), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), endocytic vesicle (GO:0030139), nuclear membrane (GO:0031965), intracellular membrane-bounded organelle (GO:0043231), nucleus (GO:0005634), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphatidylinositol kinase activity	2
intracellular anatomical structure	2
cytoplasm	2
intracellular membrane-bounded organelle	2
cellular response to nutrient levels	1
cellular response to stress	1
response to starvation	1
cell motility	1
phosphatidylinositol phosphate biosynthetic process	1
intracellular signaling cassette	1
intracellular signal transduction	1
vacuole organization	1
macroautophagy	1
primary metabolic process	1
autophagosome assembly	1
autophagy	1
glycerophospholipid biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phosphatidylinositol-3-phosphate biosynthetic process	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
nuclear lumen	1
endomembrane system	1
membrane	1
cell periphery	1
cytoplasmic vesicle	1
nucleus	1
nuclear envelope	1
organelle membrane	1
membrane-bounded organelle	1
intracellular organelle	1

Protein interactions and networks

STRING

1060 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3C2B	TECR	Q9NZ01	894
PIK3C2B	EPS8	Q12929	697
PIK3C2B	PIK3C2G	O75747	688
PIK3C2B	SOS1	Q07889	639
PIK3C2B	ITSN1	Q15811	626
PIK3C2B	EGFR	P00533	576
PIK3C2B	INPPL1	O15357	569
PIK3C2B	ITSN2	Q9NZM3	550
PIK3C2B	PIK3R5	Q8WYR1	547
PIK3C2B	NME2	P22392	546
PIK3C2B	KIT	P10721	532
PIK3C2B	PIK3CA	P42336	530
PIK3C2B	MTM1	Q13496	518
PIK3C2B	PIK3CB	P42338	511
PIK3C2B	EGF	P01133	508

IntAct

96 interactions, top by confidence:

A	B	Type	Score
PIK3C2B	GRB2	psi-mi:“MI:0915”(physical association)	0.850
PIK3C2B	EGFR	psi-mi:“MI:0915”(physical association)	0.810
PIK3C2B	EGFR	psi-mi:“MI:0407”(direct interaction)	0.810
EGFR	PIK3C2B	psi-mi:“MI:0915”(physical association)	0.810
YWHAZ	PIK3C2B	psi-mi:“MI:0915”(physical association)	0.790
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
YWHAB	BLTP3B	psi-mi:“MI:2364”(proximity)	0.610
PIK3C2B	TRIM27	psi-mi:“MI:0915”(physical association)	0.600
PIK3C2B	TRIM27	psi-mi:“MI:0403”(colocalization)	0.600
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
YWHAG	SHTN1	psi-mi:“MI:0914”(association)	0.560
PIK3C2B	SFN	psi-mi:“MI:0915”(physical association)	0.540
SH3YL1	PIK3C2B	psi-mi:“MI:0914”(association)	0.530
YWHAQ	IGLC7	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
GRB2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.530
YWHAZ	BLTP3B	psi-mi:“MI:0914”(association)	0.530

BioGRID (82): PIK3C2B (Two-hybrid), PIK3C2B (Affinity Capture-MS), FASN (Co-fractionation), PIK3C2B (Affinity Capture-MS), PIK3C2B (Affinity Capture-MS), PIK3C2B (PCA), PIK3C2B (Affinity Capture-Luminescence), PIK3C2B (Affinity Capture-MS), PIK3C2B (Affinity Capture-MS), PIK3C2B (Affinity Capture-MS), PIK3C2B (Reconstituted Complex), PIK3C2B (Affinity Capture-MS), PIK3C2B (Affinity Capture-RNA), PIK3C2B (Affinity Capture-MS), PIK3C2B (Affinity Capture-MS)

ESM2 similar proteins: A0A072VIM5, A0A0K0PU92, A0JM23, A2CIR7, F4IG73, F4JD14, G3LSH3, G8GTN7, O00750, O42132, O75460, O80560, P03372, P0CI65, P50241, P50242, P57717, P57753, Q0JJ01, Q29040, Q2HW56, Q2QXZ2, Q2RAQ5, Q53AD2, Q5D0W8, Q5M9H0, Q5YLM1, Q5ZLG9, Q6AZT7, Q6KAE5, Q6NLQ8, Q6PJI9, Q6WQJ1, Q7EZ44, Q7T0L6, Q7TNH6, Q7XAP4, Q7Z494, Q8C0M0, Q8CFE5

Diamond homologs: A0A075F932, A0FGR8, A4IJ05, K8FE10, O00445, O00750, O08625, O08835, O35681, O43581, P04409, P05128, P05129, P05130, P05696, P10102, P10829, P13677, P17252, P20444, P21521, P21579, P21707, P24505, P24506, P24507, P29101, P34693, P40748, P40749, P41823, P41885, P46096, P46097, P47191, P47708, P47709, P47861, P48018, P50232

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
TRIM27	down-regulates	PIK3C2B	ubiquitination
CH5132799	down-regulates	PIK3C2B	“chemical inhibition”
PI-103	down-regulates	PIK3C2B	“chemical inhibition”
EGFR	up-regulates	PIK3C2B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 53 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	164.6×	8e-15
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	145.2×	2e-14
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	127.1×	3e-12
Activation of BH3-only proteins	8	107.4×	3e-13
FOXO-mediated transcription	7	63.5×	6e-10
Intrinsic Pathway for Apoptosis	8	63.3×	2e-11
RHO GTPases activate PKNs	7	60.0×	9e-10
SARS-CoV-1-host interactions	8	38.0×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
protein targeting	5	40.7×	4e-05
epidermal growth factor receptor signaling pathway	6	33.0×	2e-05
phosphatidylinositol 3-kinase/protein kinase B signal transduction	5	23.4×	4e-04
intracellular protein localization	7	16.3×	5e-05
positive regulation of ERK1 and ERK2 cascade	5	9.5×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	186
Likely benign	41
Benign	23

Top pathogenic / likely-pathogenic (0)

SpliceAI

5653 predictions. Top by Δscore:

Variant	Effect	Δscore
1:204425036:ACCAA:A	acceptor_gain	1.0000
1:204425037:CCAA:C	acceptor_gain	1.0000
1:204425037:CCAAC:C	acceptor_gain	1.0000
1:204425038:CAA:C	acceptor_gain	1.0000
1:204425038:CAAC:C	acceptor_gain	1.0000
1:204425039:AA:A	acceptor_gain	1.0000
1:204425039:AACTG:A	acceptor_loss	1.0000
1:204425040:ACTGC:A	acceptor_loss	1.0000
1:204425041:C:CC	acceptor_gain	1.0000
1:204425041:CT:C	acceptor_loss	1.0000
1:204425048:CA:C	acceptor_gain	1.0000
1:204425049:A:C	acceptor_gain	1.0000
1:204425612:CCAT:C	donor_gain	1.0000
1:204425737:AGTTG:A	acceptor_gain	1.0000
1:204425738:GTTG:G	acceptor_gain	1.0000
1:204425739:TTG:T	acceptor_gain	1.0000
1:204425740:TG:T	acceptor_gain	1.0000
1:204425741:GCTAC:G	acceptor_loss	1.0000
1:204425742:C:CC	acceptor_gain	1.0000
1:204425742:C:CG	acceptor_loss	1.0000
1:204427643:CTTA:C	donor_loss	1.0000
1:204427644:TTACC:T	donor_loss	1.0000
1:204427645:T:TG	donor_loss	1.0000
1:204427646:A:AC	donor_gain	1.0000
1:204427647:C:CC	donor_gain	1.0000
1:204427647:CCAAG:C	donor_gain	1.0000
1:204428135:GTACC:G	donor_loss	1.0000
1:204428136:TACC:T	donor_loss	1.0000
1:204428137:A:T	donor_loss	1.0000
1:204428216:TCACA:T	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000028000 (1:204474553 C>A,T), RS1000096765 (1:204481457 T>C), RS1000098724 (1:204434902 C>T), RS1000201628 (1:204457999 G>A), RS1000227326 (1:204478487 A>G), RS1000253973 (1:204458346 C>T), RS1000289165 (1:204440380 C>A,T), RS1000350042 (1:204448885 G>A), RS1000356195 (1:204487256 C>A), RS1000411083 (1:204494182 A>T), RS1000446540 (1:204474894 C>T), RS1000449325 (1:204452697 C>T), RS1000486324 (1:204494501 C>A), RS1000531643 (1:204428631 T>C), RS1000581974 (1:204442515 C>A,T)

Disease associations

OMIM: gene MIM:602838 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
familial partial epilepsy	Moderate	Autosomal dominant

Mondo (1): familial partial epilepsy (MONDO:0017704)

Orphanet (0):

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001930_14	Breast cancer	2.000000e-12
GCST001942_20	Prostate cancer	2.000000e-11
GCST006108_1	Facial morphology	9.000000e-07
GCST006481_25	Lung function (FEV1)	5.000000e-08
GCST006922_4	Regular attendance at a religious group	3.000000e-08
GCST007429_98	Lung function (FVC)	2.000000e-13
GCST007430_87	Peak expiratory flow	2.000000e-19
GCST007432_107	FEV1	5.000000e-18
GCST009524_131	Household income (MTAG)	4.000000e-08
GCST009524_191	Household income (MTAG)	2.000000e-08
GCST010135_42	Oily fish consumption	2.000000e-08
GCST010140_32	Pork consumption	2.000000e-08
GCST010142_21	Fish- and plant-related diet	9.000000e-10

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004743	facial morphology
EFO:0004314	forced expiratory volume
EFO:0009592	social interaction measurement
EFO:0004312	vital capacity
EFO:0009718	peak expiratory flow
EFO:0009695	household income
EFO:0008111	diet measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5554 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

16 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 116,961 (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
CHEMBL554	LAPATINIB	4	69,326
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL2017974	BUPARLISIB	3	6,568
CHEMBL2387080	TASELISIB	3	3,473
CHEMBL592445	GEDATOLISIB	3	3,177
CHEMBL603469	LESTAURTINIB	3
CHEMBL1684984	IZORLISIB	2	1,147
CHEMBL1922094	APITOLISIB	2	3,070
CHEMBL230011	TG100-115	2	1,504
CHEMBL3188551	GSK-2636771	2	1,814
CHEMBL4084907	BIMIRALISIB	2	1,625
CHEMBL4558527	AZD-8154	2	19
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL586702	ZSTK-474	2	2,827
CHEMBL1908394	GSK-461364	1	1,093

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
PI-103	Inhibition	8.0	pIC50
torin 2	Inhibition	7.61	pIC50

Binding affinities (BindingDB)

125 measured of 288 human assays (288 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
9-(4-hydroxybicyclo[2.2.1]heptan-1-yl)-7-methyl-2-((7-methyl-[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	0.07 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
4-{6-chloroimidazo[1,2-a]pyridin-3-yl}-2-[(2-methyl-5-nitrobenzene)sulfonyl]-1,3-thiazole	IC50	2.8 nM
N-[8-(1H-imidazol-5-yl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl]-1,2,3,4-tetrahydroisoquinolin-8-amine	KD	5 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
9-(3-fluorobicyclo[1.1.1]pentan-1-yl)-7-methyl-2-((6-methylbenzo[d][1,3]dioxol-5-yl)amino)-7,9-dihydro-8H-purin-8-one	IC50	5.5 nM	US-20250263753: BRIDGED CYCLE-BASED INHIBITORS OF DNA-DEPENDENT PROTEIN KINASE AND COMPOSITIONS AND APPLICATION IN GENE EDITING
thienopyrimidine derivative, 1	IC50	8 nM
8-(1H-imidazol-5-yl)-2-methyl-N-[2-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-amine	KD	9 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
N’-[(1E)-{6-bromoimidazo[1,2-a]pyridin-3-yl}methylidene]-N,2-dimethyl-5-nitrobenzene-1-sulfonohydrazide	IC50	10 nM
2-methyl-6-morpholin-4-yl-3-N-[2-piperidin-4-yl-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	11 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
US10087187, Compound 46	KD	11 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
8-(1H-imidazol-5-yl)-2-methyl-6-morpholin-4-yl-N-[2-(morpholin-4-ylmethyl)-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazin-3-amine	KD	12 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-[2-(morpholin-4-ylmethyl)-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	15 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]methylamino]propan-1-ol	KD	16 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-(3-methyl-2-piperidin-4-ylphenyl)-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	16 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[3-(3-chloro-2-methylanilino)-8-(1H-imidazol-5-yl)-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methanol	KD	17 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-[2-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	20 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[4-[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]piperidin-1-yl]ethanol	KD	28 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-(2,3-dimethylphenyl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	31 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
1-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]methyl]pyrrolidin-3-ol	KD	31 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
N-(3-fluoro-2-methylphenyl)-8-(1H-imidazol-5-yl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-amine	KD	33 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-[2-[(3-methylsulfonylazetidin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	34 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-(1,2,3,4-tetrahydroisoquinolin-5-yl)imidazo[1,2-b]pyridazine-3,8-diamine	KD	34 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-[2-(pyrrolidin-1-ylmethyl)-3-(trifluoromethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	35 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
1-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-(trifluoromethyl)phenyl]methyl]azetidin-3-ol	KD	40 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-[3-fluoro-2-(morpholin-4-ylmethyl)phenyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	42 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-N-(2-morpholin-4-ylphenyl)-8-(1H-pyrazol-5-yl)imidazo[1,2-b]pyridazin-3-amine	KD	44 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-[2-[(1,1-dioxo-1,4-thiazinan-4-yl)methyl]-3-(trifluoromethyl)phenyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	47 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-N-[2-[(3-methylsulfonylpyrrolidin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	47 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-(hydroxymethyl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-8-carboxylic acid	KD	48 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
8-(1H-imidazol-2-yl)-2-methyl-N-[2-methyl-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-amine	KD	49 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-[(3-chloro-2-methylphenyl)methyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-8-carboxylic acid	KD	56 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-[2-(morpholin-4-ylmethyl)phenyl]imidazo[1,2-b]pyridazine-3,8-diamine	KD	56 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[8-(1H-imidazol-5-yl)-6-(2-methylmorpholin-4-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]imidazo[1,2-b]pyridazin-2-yl]methanol	KD	58 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-3-[2-methyl-3-(trifluoromethyl)anilino]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-8-carboxylic acid	KD	58 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
N-[[8-(1H-imidazol-2-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methyl]acetamide	KD	59 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[4-[2-(hydroxymethyl)-8-(1H-imidazol-5-yl)-3-[2-methyl-3-(trifluoromethyl)anilino]imidazo[1,2-b]pyridazin-6-yl]morpholin-2-yl]methanol	KD	62 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-[(2,3-dimethylphenyl)methyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-8-carboxylic acid	KD	69 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-N-(2-morpholin-4-ylphenyl)imidazo[1,2-b]pyridazine-3,8-diamine	KD	69 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
1-[8-(1H-imidazol-2-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]ethanol	KD	71 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-[2-[(1,1-dioxo-1lambda6-thia-6-azaspiro[3.3]heptan-6-yl)methyl]-3-(trifluoromethyl)phenyl]-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	73 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[[8-(1H-imidazol-2-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methylamino]ethanol	KD	74 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[[2-[(8-amino-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazin-3-yl)amino]-6-fluorophenyl]methylamino]propan-1-ol	KD	75 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-(aminomethyl)-3-N-[2-methyl-3-(trifluoromethyl)phenyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	75 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[8-(1H-imidazol-5-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methanol	KD	80 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-(2-methylmorpholin-4-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]imidazo[1,2-b]pyridazine-8-carboxylic acid	KD	83 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[8-(1H-imidazol-2-yl)-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methanol	KD	85 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-(1,2,3,4-tetrahydroisoquinolin-8-ylmethyl)imidazo[1,2-b]pyridazin-8-amine	KD	98 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-[[8-amino-3-[[2-methyl-3-(trifluoromethyl)phenyl]methyl]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methylamino]ethanol	KD	105 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
3-N-(3-fluoro-2-methylphenyl)-2-methyl-6-morpholin-4-ylimidazo[1,2-b]pyridazine-3,8-diamine	KD	105 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
2-methyl-6-morpholin-4-yl-3-(2-morpholin-4-ylanilino)imidazo[1,2-b]pyridazine-8-carboxylic acid	KD	117 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors
[8-amino-3-[2-methyl-3-(trifluoromethyl)anilino]-6-morpholin-4-ylimidazo[1,2-b]pyridazin-2-yl]methyl 2-aminopropanoate	KD	120 nM	US-10087187: Imidazopyridazine derivatives as PI3KB inhibitors

ChEMBL bioactivities

246 potent at pChembl≥5 of 259 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	Kd	0.1	nM	CHEMBL5803247
9.70	Kd	0.2	nM	CHEMBL5894050
9.70	IC50	0.2	nM	CHEMBL5878424
9.60	IC50	0.251	nM	CHEMBL5877033
9.52	Kd	0.3	nM	CHEMBL5831673
9.40	Kd	0.4	nM	CHEMBL3956037
9.34	Kd	0.46	nM	GEDATOLISIB
9.30	Kd	0.5	nM	CHEMBL6018580
9.30	Kd	0.5	nM	CHEMBL5988647
9.30	Kd	0.5	nM	CHEMBL5888478
9.30	Kd	0.5	nM	CHEMBL5268567
9.30	IC50	0.501	nM	CHEMBL5757074
9.22	Kd	0.6	nM	CHEMBL6061149
9.20	IC50	0.631	nM	CHEMBL6023527
9.15	Kd	0.7	nM	CHEMBL5989927
9.15	Kd	0.7	nM	CHEMBL5872858
9.15	Kd	0.7	nM	CHEMBL5817241
9.10	IC50	0.7943	nM	CHEMBL5091438
9.10	Kd	0.8	nM	CHEMBL5888478
9.05	Kd	0.9	nM	CHEMBL5842791
9.05	Kd	0.9	nM	CHEMBL5799166
9.00	IC50	1	nM	CHEMBL5077865
9.00	IC50	1	nM	CHEMBL5982824
9.00	IC50	1	nM	CHEMBL5824614
8.96	Kd	1.1	nM	CHEMBL5903970
8.96	Kd	1.1	nM	CHEMBL6001051
8.96	Kd	1.1	nM	CHEMBL6002102
8.92	Kd	1.2	nM	CHEMBL3991283
8.92	Kd	1.2	nM	CHEMBL3974658
8.92	Kd	1.2	nM	CHEMBL5799166
8.92	Kd	1.2	nM	CHEMBL5841991
8.90	IC50	1.26	nM	CHEMBL5864974
8.89	Kd	1.3	nM	CHEMBL3991283
8.89	Kd	1.3	nM	CHEMBL5807461
8.89	Kd	1.3	nM	CHEMBL3928423
8.89	Kd	1.3	nM	CHEMBL5930691
8.89	Kd	1.3	nM	CHEMBL5860371
8.85	Kd	1.4	nM	CHEMBL3916621
8.85	Kd	1.4	nM	CHEMBL3970860
8.85	Kd	1.4	nM	CHEMBL5930691
8.82	Kd	1.5	nM	CHEMBL3991283
8.82	Kd	1.5	nM	CHEMBL5783879
8.80	Kd	1.6	nM	CHEMBL5860630
8.80	IC50	1.58	nM	CHEMBL5927544
8.80	IC50	1.58	nM	CHEMBL5821218
8.80	IC50	1.58	nM	CHEMBL5967127
8.77	Kd	1.7	nM	CHEMBL5803568
8.74	Kd	1.8	nM	CHEMBL5944493
8.72	Kd	1.9	nM	CHEMBL6065963
8.72	Kd	1.9	nM	CHEMBL3955003

PubChem BioAssay actives

97 with measured affinity, of 372 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
1-[4-[4-(dimethylamino)piperidine-1-carbonyl]phenyl]-3-[4-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)phenyl]urea	1451362: Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammalian expression system by Kinomescan assay	kd	0.0005	uM
24-[(1S)-1-cyclopropylethyl]-3-methyl-20,20-dioxo-16-oxa-20lambda6,30-dithia-4,6,13,19,24,29-hexazapentacyclo[19.6.1.12,5.17,11.022,26]triaconta-1(27),2,4,7,9,11(29),21(28),22(26)-octaene-12,23-dione	1807063: Inhibition of PIK3C2B (unknown origin) assessed as reduction in substrate phosphorylation by FRET Adapta assay	ic50	0.0008	uM
2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)-2-pyridinyl]amino]-1,3-thiazol-5-yl]-N-(oxetan-3-yl)-3-oxo-1H-isoindole-4-sulfonamide	1807063: Inhibition of PIK3C2B (unknown origin) assessed as reduction in substrate phosphorylation by FRET Adapta assay	ic50	0.0010	uM
2-[(1S)-1-cyclopropylethyl]-5-[4-methyl-2-[[6-(2-oxopyrrolidin-1-yl)-2-pyridinyl]amino]-1,3-thiazol-5-yl]-7-methylsulfonyl-3H-isoindol-1-one	1807063: Inhibition of PIK3C2B (unknown origin) assessed as reduction in substrate phosphorylation by FRET Adapta assay	ic50	0.0032	uM
N-hydroxy-7-[2-[3-(hydroxymethyl)phenyl]-6-morpholin-4-ylpurin-9-yl]heptanamide	1702226: Inhibition of PI3K2beta (unknown origin)	kd	0.0049	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	624877: Binding constant for PIK3C2B kinase domain	kd	0.0073	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol;hydrochloride	289257: Inhibition of glu-tagged PI3K C2-beta expressed in SF9/Baculovirus system by SPA	ic50	0.0100	uM
3-(6-morpholin-4-yl-8-oxa-3,5,10-triazatricyclo[7.4.0.02,7]trideca-1(9),2(7),3,5,10,12-hexaen-4-yl)phenol	1798508: Scintillation Proximity Assay from Article 10.1016/j.bmc.2007.05.070: “Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors.”	ic50	0.0100	uM
9-(6-amino-3-pyridinyl)-1-[3-(trifluoromethyl)phenyl]benzo[h][1,6]naphthyridin-2-one	2198479: Inhibition of PIK3C2B (unknown origin) by drug competition for substrate binding based assay	ec50	0.0245	uM
3-(6-morpholin-4-yl-8-oxa-5,10-diazatricyclo[7.4.0.02,7]trideca-1(9),2,4,6,10,12-hexaen-4-yl)phenol	1321985: Inhibition of PI3KC2beta (unknown origin) expressed in HEK293 cells using phosphatidylinositol and gamma-32P-ATP incubated for 20 mins by TLC assay or high-throughput membrane capture assay	ic50	0.0260	uM
4-[2-[(6-methoxy-3-pyridinyl)amino]-5-[(4-methylsulfonylpiperazin-1-yl)methyl]-3-pyridinyl]-6-methyl-1,3,5-triazin-2-amine	699581: Inhibition of PIK3C2beta	ic50	0.0290	uM
N-[5-[2-[(1S)-1-cyclopropylethyl]-7-methylsulfonyl-1-oxo-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]acetamide	1497519: Inhibition of PI3KC2beta (unknown origin)	ic50	0.0316	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	1451362: Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammalian expression system by Kinomescan assay	kd	0.0400	uM
6-amino-N-[7-methoxy-8-[(3-nitrophenyl)methoxy]-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyridine-3-carboxamide	2019660: Inhibition of N-terminal 6His-tagged PI3KC2beta (unknown origin) expressed in Escherichia coli DH10 infected in Sf21 insect cells incubated for 60 mins in the presence of ATP by Kinase-Glo reagent based luminescence plate reader analysis	ic50	0.0430	uM
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile	1321992: Inhibition of human recombinant PI3KC2beta using substrate PI incubated for 1 hr by Adapta kinase assay	ic50	0.0440	uM
1-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]cyclopropane-1-carbonitrile	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.0440	uM
N-(7,8-dimethoxy-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene)pyridine-3-carboxamide	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.0640	uM
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide	1798508: Scintillation Proximity Assay from Article 10.1016/j.bmc.2007.05.070: “Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors.”	ic50	0.1000	uM
4-(6-chloroimidazo[1,2-a]pyridin-3-yl)-2-(2-methyl-5-nitrophenyl)sulfonyl-1,3-thiazole	1798509: Scintillation Proximity Assay from Article 10.1016/j.bmc.2006.09.047: “Synthesis and biological evaluation of imidazo[1,2-a]pyridine derivatives as novel PI3 kinase p110alpha inhibitors.”	ic50	0.1000	uM
4-(6-chloroimidazo[1,2-a]pyridin-3-yl)-2-(2-methyl-5-nitrophenyl)sulfonyl-1,3-thiazole;hydrochloride	284036: Inhibition of Glu-tagged PI3K C2-beta by SPA	ic50	0.1000	uM
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide;hydrochloride	289257: Inhibition of glu-tagged PI3K C2-beta expressed in SF9/Baculovirus system by SPA	ic50	0.1000	uM
N-[5-[4-chloro-3-(2-hydroxyethylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]acetamide	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.1400	uM
4-[4-[2-(difluoromethyl)benzimidazol-1-yl]-6-morpholin-4-yl-1,3,5-triazin-2-yl]morpholine	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.1800	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624877: Binding constant for PIK3C2B kinase domain	kd	0.2200	uM
3-(4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenol;hydrochloride	289257: Inhibition of glu-tagged PI3K C2-beta expressed in SF9/Baculovirus system by SPA	ic50	0.2200	uM
3-(4-morpholin-4-ylthieno[3,2-d]pyrimidin-2-yl)phenol	1798508: Scintillation Proximity Assay from Article 10.1016/j.bmc.2007.05.070: “Synthesis and biological evaluation of sulfonylhydrazone-substituted imidazo[1,2-a]pyridines as novel PI3 kinase p110alpha inhibitors.”	ic50	0.2200	uM
(2S)-2-amino-N-[5-[6-chloro-5-[(4-methylphenyl)sulfonylamino]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide	1361702: Inhibition of N-terminal GST-tagged recombinant human PIK3C2B catalytic domain expressed in Baculovirus expression system using PI as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr in presence of 50 uM ATP by ADP-Glo luminescence assay	ic50	0.2479	uM
7-[2-(2-aminopyrimidin-5-yl)-4-morpholin-4-ylpyrrolo[2,3-d]pyrimidin-7-yl]-N-hydroxyheptanamide	1702226: Inhibition of PI3K2beta (unknown origin)	kd	0.2600	uM
2-methyl-2-[4-[2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrazol-1-yl]propanamide	750502: Inhibition of PI3KC2beta (unknown origin)	ic50	0.2920	uM
6-(1,3-benzodioxol-5-yl)-N-methyl-N-[(2-methyl-1,3-thiazol-4-yl)methyl]quinazolin-4-amine	594087: Binding affinity to human PIK3C2B	kd	0.3400	uM
4-[(3-chloro-4-fluorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1321985: Inhibition of PI3KC2beta (unknown origin) expressed in HEK293 cells using phosphatidylinositol and gamma-32P-ATP incubated for 20 mins by TLC assay or high-throughput membrane capture assay	ic50	0.3700	uM
4-[(3-chloro-4-fluorophenyl)methyl]-6-[(E)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.3700	uM
6-(1,3-benzodioxol-5-yl)-N-(oxolan-3-ylmethyl)quinazolin-4-amine	594087: Binding affinity to human PIK3C2B	kd	0.4100	uM
N-[3-(3-pyridin-3-yl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)phenyl]-2-thiophen-2-ylacetamide	1876219: Inhibition of PIK3C2beta (unknown origin)	ic50	0.4300	uM
N-(1-methylpiperidin-4-yl)-4-[4-(2-oxo-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-1-yl)-2-(trifluoromethyl)phenyl]benzamide	603284: Inhibition of PI3K C2beta	ic50	0.4370	uM
(2S)-1-N-[5-(2-tert-butyl-1,3-thiazol-4-yl)-4-methyl-1,3-thiazol-2-yl]pyrrolidine-1,2-dicarboxamide	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.4620	uM
N-[4-morpholin-4-yl-2-[3-(naphthalen-1-ylsulfonylamino)phenyl]quinazolin-6-yl]acetamide	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.5300	uM
N-[4-morpholin-4-yl-2-[3-(naphthalen-2-ylsulfonylamino)phenyl]quinazolin-6-yl]acetamide	1321971: Inhibition of GST-tagged human recombinant PI3KC2beta expressed in Sf9 cells	ic50	0.5300	uM
5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyrimidin-2-amine	1451362: Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammalian expression system by Kinomescan assay	kd	0.5400	uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-yl-3,4-dihydrobenzo[h][1,6]naphthyridin-2-one	2198479: Inhibition of PIK3C2B (unknown origin) by drug competition for substrate binding based assay	ec50	0.5490	uM
1-[4-(4-propanoylpiperazin-1-yl)-3-(trifluoromethyl)phenyl]-9-quinolin-3-ylbenzo[h][1,6]naphthyridin-2-one	517861: Inhibition of PI3K-C2 beta	ic50	0.5490	uM
(2S)-1-[4-[[2-(2-aminopyrimidin-5-yl)-7-methyl-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl]piperazin-1-yl]-2-hydroxypropan-1-one	1451362: Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammalian expression system by Kinomescan assay	kd	0.5800	uM
N-[2-[3-(benzenesulfonamido)phenyl]-4-morpholin-4-ylquinazolin-6-yl]acetamide	1177095: Inhibition of human PI3KC2beta by non-radiometric ADP-Glo assay	ic50	0.6300	uM
Lapatinib	624877: Binding constant for PIK3C2B kinase domain	kd	0.6700	uM
5-(4,6-dimorpholin-4-yl-1,3,5-triazin-2-yl)-4-(trifluoromethyl)pyridin-2-amine	1451362: Binding affinity to human PI3KC2beta (M1 to L1634 residues) expressed in mammalian expression system by Kinomescan assay	kd	0.8200	uM
(2S)-2-amino-N-[5-[6-chloro-5-[(3-methylphenyl)sulfonylamino]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide	1361702: Inhibition of N-terminal GST-tagged recombinant human PIK3C2B catalytic domain expressed in Baculovirus expression system using PI as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr in presence of 50 uM ATP by ADP-Glo luminescence assay	ic50	0.8823	uM
(2S)-2-amino-N-[5-[6-chloro-5-[(2-methylphenyl)sulfonylamino]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide	1361702: Inhibition of N-terminal GST-tagged recombinant human PIK3C2B catalytic domain expressed in Baculovirus expression system using PI as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr in presence of 50 uM ATP by ADP-Glo luminescence assay	ic50	1.0960	uM
N-[4-(3-hydroxyphenyl)-1,3-thiazol-2-yl]-2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanylacetamide	2019680: Inhibition of PI3KC2beta (unknown origin) using PI lipid kinase as substrate in the presence of 10 uM ATP by Adapta universal kinase assay	ic50	1.4000	uM
Midostaurin	507672: Binding affinity to PIK3C2B	kd	1.4000	uM
2-[4-oxo-3-(2-phenylethyl)pteridin-2-yl]sulfanyl-N-phenylacetamide	2019677: Inhibition of PI3KC2beta (unknown origin)	ic50	1.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	affects cotreatment, decreases expression	3
Cisplatin	affects cotreatment, increases expression, decreases response to substance	2
Dexamethasone	increases expression, affects cotreatment	2
Smoke	decreases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
terbufos	increases methylation	1
hydroxyhydroquinone	decreases expression	1
afimoxifene	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	decreases expression	1
cupric chloride	decreases expression	1
myricetin	decreases expression	1
nefazodone	affects cotreatment, decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
fenpyroximate	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
pyrimidifen	decreases expression	1
clothianidin	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1

ChEMBL screening assays

212 unique, capped per target: 211 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1037986	Binding	Binding affinity to human PIK3C2beta at 200 nM by cell-based competition binding assay relative to control in presence of DTT	Staurosporine tethered peptide ligands that target cAMP-dependent protein kinase (PKA): optimization and selectivity profiling. — Bioorg Med Chem
CHEMBL4683370	ADMET	Inhibition of human PIK3C2beta by ADP-Glo kinase assay	Discovery of 6’-chloro-N-methyl-5’-(phenylsulfonamido)-[3,3’-bipyridine]-5-carboxamide (CHMFL-PI4K-127) as a novel Plasmodium falciparum PI(4)K inhibitor with potent antimalarial activity against both blood and liver stages of Plasmodium. — Eur J Med Chem

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7X8	Ubigene A-549 PIK3C2B KO	Cancer cell line	Male
CVCL_D8SN	Ubigene HCT 116 PIK3C2B KO	Cancer cell line	Male
CVCL_D9N6	Ubigene HEK293 PIK3C2B KO	Transformed cell line	Female
CVCL_E0KJ	Ubigene HeLa PIK3C2B KO	Cancer cell line	Female
CVCL_TD58	HAP1 PIK3C2B (-) 1	Cancer cell line	Male
CVCL_TD59	HAP1 PIK3C2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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