PIK3R2

Summary

PIK3R2 (phosphoinositide-3-kinase regulatory subunit 2, HGNC:8980) is a protein-coding gene on chromosome 19p13.11, encoding Phosphatidylinositol 3-kinase regulatory subunit beta (O00459). Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). In precision oncology, BRAF V600E AND PIK3R2 N561D is associated with resistance to Vemurafenib in Melanoma (CIViC Level D); 1 further curated variant–drug associations are listed below.

Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that phosphorylates phosphatidylinositol and similar compounds, creating second messengers important in growth signaling pathways. PI3K functions as a heterodimer of a regulatory and a catalytic subunit. The protein encoded by this gene is a regulatory component of PI3K. Three transcript variants, one protein coding and the other two non-protein coding, have been found for this gene.

Source: NCBI Gene 5296 — RefSeq curated summary.

At a glance

• Gene–disease (curated): overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 535 total — 5 pathogenic, 6 likely-pathogenic (top 6% of genes corpus-wide)
• GTEx eGene: eQTL in 14 tissues, sQTL in 8 (q < 0.05)
• Phenotypes (HPO): 38
• Drug target: yes — 26 via a complex or family; 6 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.76 (unconstrained)
• MANE Select transcript: NM_005027
• Interaction hub: 1,774 STRING partners (top 10% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8980
Approved symbol	PIK3R2
Name	phosphoinositide-3-kinase regulatory subunit 2
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	P85B, p85, p85beta, p85-BETA
Ensembl gene	ENSG00000105647
Ensembl biotype	protein_coding
OMIM	603157
Entrez	5296

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 17 protein_coding, 12 nonsense_mediated_decay, 5 retained_intron

MANE Select: ENST00000222254

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 2, TSL 5: 2

ENST00000222254, ENST00000426902, ENST00000459743, ENST00000464016, ENST00000474310, ENST00000600533, ENST00000617130, ENST00000617642, ENST00000672815, ENST00000674682, ENST00000675271, ENST00000874453, ENST00000874454, ENST00000874455, ENST00000874456, ENST00000874457, ENST00000874458, ENST00000874459, ENST00000925096, ENST00000925097, ENST00000925098, ENST00000925099, ENST00000925100, ENST00000925101, ENST00000965709, ENST00000965710, ENST00000978819, ENST00001014502, ENST00001014503, ENST00001014504, ENST00001072682, ENST00001072683, ENST00001112297, ENST00001139855

RefSeq mRNA: 1 — MANE Select: NM_005027 NM_005027

CCDS: CCDS12371

Canonical transcript exons

ENST00000222254 — 16 exons

Exon	Start	End
ENSE00000893034	18169087	18170532
ENSE00003067609	18153163	18153294
ENSE00003464305	18161966	18162051
ENSE00003474719	18155457	18156201
ENSE00003498129	18168726	18168896
ENSE00003498230	18161279	18161495
ENSE00003502685	18168475	18168546
ENSE00003506088	18166160	18166302
ENSE00003516250	18162202	18162310
ENSE00003540261	18162408	18162506
ENSE00003546729	18162967	18163147
ENSE00003571819	18163263	18163388
ENSE00003603229	18160471	18160563
ENSE00003645468	18160919	18160969
ENSE00003662245	18161054	18161185
ENSE00003704990	18167130	18167306

Expression profiles

Bgee: expression breadth ubiquitous, 138 present calls, max score 97.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.8949 / max 299.1967, expressed in 1804 samples.

Highest expression (Bgee): cortical plate, ganglionic eminence, stromal cell of endometrium, ventricular zone, adrenal gland cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PIK3R2 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 14 tissues and its splicing (sQTL) in 8 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 22 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	1.1e-09	+0.70	19:18166046:T:C
Skin Not Sun Exposed Suprapubic	sqtl	2.0e-06	+0.66	19:18166046:T:C
Nerve Tibial	sqtl	1.1e-05	+0.65	19:18166046:T:C
Adipose Subcutaneous	sqtl	1.5e-04	+0.58	19:18162600:A:G
Nerve Tibial	eqtl	1.8e-04	+0.20	19:18169692:G:A
Skin Sun Exposed Lower leg	eqtl	9.8e-04	+0.14	19:18139882:T:C
Cells Cultured fibroblasts	eqtl	1.1e-03	+0.25	19:18169692:G:A
Brain Spinal cord cervical c-1	eqtl	1.5e-03	-0.56	19:18139882:T:C
Artery Tibial	eqtl	1.6e-03	+0.35	19:18108982:A:T
Adipose Subcutaneous	eqtl	3.2e-03	+0.20	19:18169692:G:A
Brain Cortex	eqtl	4.1e-03	+0.73	19:18530893:G:A
Skin Not Sun Exposed Suprapubic	eqtl	4.1e-03	-0.27	19:18426234:G:A
Brain Frontal Cortex BA9	eqtl	4.6e-03	-0.22	19:18163821:C:CTAAAAACAAA
Pituitary	sqtl	6.2e-03	+0.83	19:18121000:T:C
Esophagus Mucosa	eqtl	8.3e-03	+0.09	19:18153687:C:T
Brain Nucleus accumbens basal ganglia	eqtl	1.1e-02	-0.46	19:18181642:C:T
Muscle Skeletal	eqtl	1.7e-02	+0.11	19:17824817:T:C
Artery Tibial	sqtl	2.3e-02	+0.51	19:18166046:T:C
Thyroid	eqtl	2.6e-02	-0.47	19:17963905:T:A
Prostate	sqtl	3.2e-02	-2.44	19:17593516:G:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
174596	33.7135	1800
174597	0.6441	383
174598	0.3111	63
174599	0.1761	56
174600	0.0501	25

Top tissues by expression

showing 100 of 138 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.66	gold quality
ganglionic eminence	UBERON:0004023	96.01	gold quality
stromal cell of endometrium	CL:0002255	95.80	gold quality
ventricular zone	UBERON:0003053	95.40	gold quality
right adrenal gland cortex	UBERON:0035827	93.75	gold quality
right adrenal gland	UBERON:0001233	93.11	gold quality
prefrontal cortex	UBERON:0000451	93.06	gold quality
Ammon’s horn	UBERON:0001954	92.83	gold quality
frontal cortex	UBERON:0001870	92.75	gold quality
frontal lobe	UBERON:0016525	92.75	gold quality
superior frontal gyrus	UBERON:0002661	92.65	gold quality
left adrenal gland	UBERON:0001234	92.38	gold quality
left adrenal gland cortex	UBERON:0035825	92.34	gold quality
right frontal lobe	UBERON:0002810	92.23	gold quality
cerebral cortex	UBERON:0000956	92.15	gold quality
nucleus accumbens	UBERON:0001882	92.00	gold quality
primary visual cortex	UBERON:0002436	91.91	gold quality
anterior cingulate cortex	UBERON:0009835	91.88	gold quality
temporal lobe	UBERON:0001871	91.77	gold quality
amygdala	UBERON:0001876	91.66	gold quality
adrenal gland	UBERON:0002369	91.12	gold quality
caudate nucleus	UBERON:0001873	90.99	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	90.77	gold quality
putamen	UBERON:0001874	90.70	gold quality
duodenum	UBERON:0002114	90.48	gold quality
Brodmann (1909) area 9	UBERON:0013540	90.30	gold quality
brain	UBERON:0000955	90.18	gold quality
esophagus mucosa	UBERON:0002469	90.18	gold quality
pituitary gland	UBERON:0000007	89.65	gold quality
adenohypophysis	UBERON:0002196	89.05	gold quality
lower esophagus mucosa	UBERON:0035834	88.24	gold quality
right ovary	UBERON:0002118	87.98	gold quality
ovary	UBERON:0000992	87.85	gold quality
left ovary	UBERON:0002119	87.76	gold quality
fallopian tube	UBERON:0003889	87.73	gold quality
ectocervix	UBERON:0012249	87.53	gold quality
right hemisphere of cerebellum	UBERON:0014890	87.18	gold quality
fundus of stomach	UBERON:0001160	87.02	gold quality
esophagus	UBERON:0001043	87.00	gold quality
endocervix	UBERON:0000458	86.96	gold quality
skin of leg	UBERON:0001511	86.86	gold quality
mucosa of transverse colon	UBERON:0004991	86.72	gold quality
apex of heart	UBERON:0002098	86.67	gold quality
zone of skin	UBERON:0000014	86.64	gold quality
gall bladder	UBERON:0002110	86.62	gold quality
cerebellum	UBERON:0002037	86.59	gold quality
cerebellar cortex	UBERON:0002129	86.46	gold quality
left uterine tube	UBERON:0001303	86.44	gold quality
cerebellar hemisphere	UBERON:0002245	86.43	gold quality
skin of abdomen	UBERON:0001416	86.34	gold quality
adult mammalian kidney	UBERON:0000082	86.24	gold quality
cortex of kidney	UBERON:0001225	86.20	gold quality
right uterine tube	UBERON:0001302	86.17	gold quality
body of stomach	UBERON:0001161	86.09	gold quality
metanephros cortex	UBERON:0010533	85.99	gold quality
vagina	UBERON:0000996	85.89	gold quality
body of uterus	UBERON:0009853	85.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.50	gold quality
placenta	UBERON:0001987	85.44	gold quality
stomach	UBERON:0000945	85.43	gold quality
hypothalamus	UBERON:0001898	85.40	gold quality
islet of Langerhans	UBERON:0000006	85.29	gold quality
heart left ventricle	UBERON:0002084	85.27	gold quality
transverse colon	UBERON:0001157	85.19	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.15	gold quality
prostate gland	UBERON:0002367	85.08	gold quality
saliva-secreting gland	UBERON:0001044	85.03	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	84.89	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	84.86	gold quality
minor salivary gland	UBERON:0001830	84.81	gold quality
myometrium	UBERON:0001296	84.72	gold quality
mucosa of stomach	UBERON:0001199	84.69	gold quality
uterine cervix	UBERON:0000002	84.68	gold quality
material anatomical entity	UBERON:0000465	84.60	gold quality
multicellular organism	UBERON:0000468	84.60	gold quality
anatomical system	UBERON:0000467	84.59	gold quality
right atrium auricular region	UBERON:0006631	84.39	gold quality
heart	UBERON:0000948	84.24	gold quality
kidney	UBERON:0002113	84.23	gold quality
small intestine	UBERON:0002108	84.22	gold quality
substantia nigra	UBERON:0002038	84.16	gold quality
colon	UBERON:0001155	84.15	gold quality
small intestine Peyer’s patch	UBERON:0003454	84.00	gold quality
intestine	UBERON:0000160	83.99	gold quality
muscle layer of sigmoid colon	UBERON:0035805	83.93	gold quality
lower esophagus	UBERON:0013473	83.88	gold quality
gastrocnemius	UBERON:0001388	83.84	gold quality
adrenal tissue	UBERON:0018303	83.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	83.84	gold quality
right lobe of liver	UBERON:0001114	83.75	gold quality
muscle of leg	UBERON:0001383	83.64	gold quality
vermiform appendix	UBERON:0001154	83.28	gold quality
urinary bladder	UBERON:0001255	83.25	gold quality
smooth muscle tissue	UBERON:0001135	83.18	gold quality
pancreas	UBERON:0001264	83.15	gold quality
right coronary artery	UBERON:0001625	83.00	gold quality
right lobe of thyroid gland	UBERON:0001119	82.72	gold quality
left lobe of thyroid gland	UBERON:0001120	82.52	gold quality
popliteal artery	UBERON:0002250	82.43	gold quality
tibial artery	UBERON:0007610	82.43	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.59

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampus	tissue	102.3	medium
Frontal cortex	tissue	69.6
Postcentral gyrus	tissue	56.9
Nucleus accumbens	tissue	54.5
Hippocampal formation	tissue	47.5
Cerebral cortex	tissue	45.8	medium
Motor cortex	tissue	45.8
Prefrontal cortex	tissue	45.3
Caudate putamen	tissue	44.0
Temporal cortex	tissue	43.9
Somatosensory cortex	tissue	42.0
Insular cortex	tissue	41.6
Basal ganglia	tissue	41.5	medium
Entorhinal cortex	tissue	41.1
Retrosplenial and cingulate cortex	tissue	39.6
Retrosplenial cortex	tissue	39.3
Occipital cortex	tissue	39.1
Amygdala	tissue	38.8
Putamen	tissue	37.8
Ventral forebrain	tissue	33.1
Olfactory bulb	tissue	32.4
Septum	tissue	28.5
Locus coeruleus	tissue	25.7
Thalamus	tissue	25.1
Skin 1	tissue	24.9	medium
Midbrain	tissue	23.6
Choroid plexus	tissue	23.2
Superior colliculi	tissue	21.5
Cerebellum	tissue	21.5	medium
Pons	tissue	20.6
Parathyroid gland	tissue	19.6	high
Corpus callosum	tissue	19.4
Duodenum	tissue	19.3	high
Hypothalamus	tissue	19.0
Substantia nigra	tissue	18.2
Spinal cord	tissue	17.7
Ovary	tissue	17.2	low
Pituitary gland	tissue	16.7
Medulla oblongata	tissue	16.3
Small intestine	tissue	15.7	high
Fallopian tube	tissue	15.7	high
Periaqueductal gray	tissue	14.9
Esophagus	tissue	14.8	medium
Adrenal gland	tissue	14.6	high
Stomach 1	tissue	14.2	medium
Salivary gland	tissue	14.1	medium
Colon	tissue	12.6	high
Cervix	tissue	12.3	medium
Vagina	tissue	12.0	medium
Heart muscle	tissue	11.9	not detected
Gallbladder	tissue	11.5	medium
Epididymis	tissue	11.4	medium
Skeletal muscle	tissue	10.9	not detected
Thymus	tissue	10.8
Urinary bladder	tissue	10.5	high
Pancreas	tissue	10.4	medium
Endometrium 1	tissue	10.1	high
Seminal vesicle	tissue	9.8	medium
Prostate	tissue	9.4	medium
Tongue	tissue	9.3

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Hippocampus, CA3 (104.5), Posterior cingulate cortex (104.5), Hippocampus, CA1 (99.5), Dentate gyrus (89.0), Hippocampus, CA2 (80.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PIK3R2 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 76 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-4307	99.82	70.45	3374

Functional genomics

gnomAD constraint: pLI 1.68e-07, LOEUF 0.76, missense Z 0.61 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000222254 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:18,155,880–18,162,269	456 / 486.6	0.94	no
19:18,162,270–18,166,279	156 / 241.0	0.65	no
19:18,166,280–18,169,291	268 / 299.1	0.90	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Mutant viruses carrying NS1 with mutations in SH3 binding motif 1 failed to interact with p85ss and induce the subsequent activation of PI3K/Akt pathway. (PMID:17881440)
• in VSMCs exposed to hyperglycemia, IGF-I stimulation of Shc facilitates the transfer of Grb2 to p85 resulting in enhanced PI3K activation and AKT phosphorylation leading to enhanced cell proliferation and migration (PMID:18420583)
• the influenza A virus NS1 protein interacts with the p85beta, but not the p85alpha, subunit of phosphatidylinositol 3-kinase (PMID:18534979)
• FGFR3 and p85 proteins interact in myeloma cells which express p85alpha and p85beta. (PMID:19286672)
• p85alpha and p85beta may recruit proteins in the endocytic machinery on Epo stimulation; mutated EpoRs from primary familial and congenital polycythemia patients lacking the 3 important tyrosines do not bind p85 or internalize on stimulation (PMID:19336760)
• PTEN-p85 association involves the unphosphorylated form of PTEN engaged within the PTEN-associated complex and also includes the p110beta isoform of PI3K. (PMID:19635806)
• Data show that mesothelin is a potential target in reducing resistance to cytotoxic drugs, and mesothelin-treated cells revealed rapid tyrosine phosphorylation of the p85 subunit of PI3K. (PMID:19747165)
• NS5A mediates activation of beta-catenin in a phosphoinositide-3 kinase-dependent fashion. (PMID:19846673)
• oncogenic p85 mutations lead to a loss of a C2-iSH2 domain contact that is required for inhibition of p110alpha by p85. (PMID:19915146)
• the PTEN phosphatase is active against the PI3K p85beta subunit and dephosphorylates a protein involved in insulin signaling where known downstream consequences are increased cell migration, motility, and invasion. (PMID:20515662)
• Macropinocytosis is regulated by interactions between Abi1 pY213 and the C-terminal SH2 domain of p85-thereby linking Abl kinase signaling to p85-dependent regulation of macropinocytosis. (PMID:20598684)
• Overexpression of SH3 domain of p85beta inhibits influenza A virus replication. (PMID:20653952)
• The crystal structure of human p85beta iSH2 determined to 3.3A resolution is reported. (PMID:21139197)
• miR-126 could target both VEGFA and PIK3R2, and its expression was decreased in human breast cancer, implying that miR-126 may play a role in tumor genesis and growth by regulating the VEGF/PI3K/AKT signaling pathway (PMID:21249429)
• study shows that p110beta nuclear localization signal and p85beta nuclear export sequence regulate p85beta/p110beta nuclear localization, supporting the idea that nuclear, but not cytoplasmic, p110beta controls cell survival (PMID:21383062)
• This paper reports the first purification of a phosphoinositide 3-kinase and shows that the protein is a heterodimer of an 85 kd regulatory subunit that mediates binding to phosphorylated proteins and a 110 kd catalytic subunit. (PMID:2174051)
• Multiple PIK3R1 and PIK3R2 mutations demonstrate gain of function, including disruption of a novel mechanism of pathway regulation wherein p85alpha dimers bind and stabilize PTEN. (PMID:21984976)
• recombinant production, crystallization and X-ray structure determination at 2.0 A resolution of the SH3 domain of human p85beta is described (PMID:22102226)
• identified mutations in AKT3, PIK3R2 and PIK3CA in 11 unrelated families with megalencephaly-capillary malformation and megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndromes (PMID:22729224)
• p85beta phosphoinositide 3-kinase subunit regulates tumor progression (PMID:22733740)
• miR-126-mediated phosphoinositide-3-kinase regulation, not only fine-tunes VEGF-signaling, but it strongly enhances the activities of Ang-1 on vessel stabilization and maturation. (PMID:22867989)
• Both alpha and beta isomers of the PI3K regulatory subunit p85 and full-length rotavirus NSP1 are important for this interaction, which results in efficient activation of the PI3K/Akt pathway during rotavirus infection. (PMID:23221569)
• Data indicate PI3K p85 mediates the interaction of beta-catenin with NF-kappaB (p65). (PMID:23583404)
• FBXL2 mediates the ubiquitylation and degradation of p85beta on cell membranes. (PMID:23604317)
• Study indicates that miR-126 is a tumor suppressor that inhibits gastric cancer cells proliferation by targeting PI3KR2, Crk and PLK2. (PMID:24969300)
• the metastasis and angiogenesis functions of miR-126-3p were mediated by LRP6 and PIK3R2. (PMID:25240815)
• The authors show that this potentiation involves reorganization of the natural CrkL-p85beta complex into a novel trimeric complex where influenza A virus NS1 serves as a bridging factor. (PMID:26099693)
• The miR-126 was found to act as proliferation suppressor targeting PIK3R2 gene and reducing p85beta (a regulatory subunit of PI3K kinase) protein translation and lower AKT kinase activity. (PMID:26384552)
• miR-3151 silencing by DNA methylation protected chronic lymphocytic leukemia cells from apoptosis by over-expression of its direct targets MADD and PIK3R2, constitutive activation of MEK/ERK and PI3K/AKT signaling , and over-expression of MCL1. (PMID:26517243)
• Constitutional and mosaic mutations in the PIK3R2 gene are associated with developmental brain disorders ranging from Bilateral perisylvian polymicrogyria with a normal head size to the megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome. (PMID:26520804)
• pik3r2 was confirmed to be a direct target of miR126 in prostate cancer. (PMID:26677064)
• indicated that miR-126 expression was negatively correlated with PIK3R2 mRNA expression (PMID:26723864)
• PIK3R2 D557H mutation causes polymicrogyria, corpus callosum hyperplasia and focal cortical dysplasia. (PMID:26860062)
• Data show that phosphoinositol-3 kinase regulatory subunit 2 (PIK3R2) mRNA is a direct target of miR-126-3p. (PMID:27191494)
• Data indicate that miR-126 overexpression in RASFs inhibits PIK3R2 expression and promotes proliferation while inhibiting apoptosis. (PMID:27729613)
• this study shows that targeted depletion of PIK3R2 induces regression of lung squamous cell carcinoma (PMID:27835880)
• Data indicate that miR-126 expression negatively correlates with p85beta in CLL patients and that miR-126 can effectively target p85beta in a cell-line system. (PMID:28299881)
• Mosaic mutations in PIK3CA or PIK3R2 which activate class 1A PI3K cause severe non-ketotic hypoglycaemia in a subset of patients, with the metabolic phenotype presumably related to the extent of mosaicism within the liver (PMID:28566443)
• USP49 inhibits non-small cell lung cancer cell growth by suppressing PIK3R2/AKT signaling. (PMID:31001918)
• p85beta regulates autophagic degradation of AXL to activate oncogenic signaling. (PMID:32385243)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3r2	ENSDARG00000018060
mus_musculus	Pik3r2	ENSMUSG00000031834
rattus_norvegicus	Pik3r2	ENSRNOG00000019228
drosophila_melanogaster	Pi3K21B	FBGN0020622
caenorhabditis_elegans	aap-1	WBGENE00000001

Paralogs (2): PIK3R3 (ENSG00000117461), PIK3R1 (ENSG00000145675)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1098772) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 11 distinct phenotype terms.

Mouse phenotype (MP)	Records
thickened cerebral cortex	1
decreased body weight	1
increased brain weight	1
decreased circulating insulin level	1
increased insulin sensitivity	1
increased brain size	1
decreased circulating creatinine level	1
decreased circulating glucose level	1
neuron hypertrophy	1
dilated brain ventricle	1
abnormal cell nucleus size	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Pongo abelii	Q5R685	99.4%	Diamond
Sus scrofa	Q7YRV6	97.5%	Diamond
Bos taurus	Q861R0	97.5%	Diamond
Xenopus laevis	Q8UUU2	80.0%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MAST3	protein-coding	23031
RAB3A	protein-coding	5864
MPV17L2	protein-coding	84769
IL12RB1	protein-coding	3594
IFI30	protein-coding	10437
PDE4C	protein-coding	5143
CIST1	protein-coding	729966

Protein

Protein identifiers

Phosphatidylinositol 3-kinase regulatory subunit beta — O00459 (reviewed: O00459)

Alternative names: Phosphatidylinositol 3-kinase 85 kDa regulatory subunit beta

All UniProt accessions (6): A0A087X257, A0A5F9ZHY3, A0A7I2U3A3, E9PFP1, O00459, V9GYJ4

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of phosphoinositide-3-kinase (PI3K), a kinase that phosphorylates PtdIns(4,5)P2 (Phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3). PIP3 plays a key role by recruiting PH domain-containing proteins to the membrane, including AKT1 and PDPK1, activating signaling cascades involved in cell growth, survival, proliferation, motility and morphology. Binds to activated (phosphorylated) protein-tyrosine kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. Indirectly regulates autophagy. Promotes nuclear translocation of XBP1 isoform 2 in a ER stress- and/or insulin-dependent manner during metabolic overloading in the liver and hence plays a role in glucose tolerance improvement.

Subunit / interactions. Heterodimer of a regulatory subunit PIK3R2 and a p110 catalytic subunit (PIK3CA, PIK3CB or PIK3CD). Interacts with AXL. Interacts with FLT1 (tyrosine-phosphorylated) and FLT4 (tyrosine-phosphorylated). Interacts with NYAP1, NYAP2 and MYO16. Interacts with FBXL2; PIK3R2 is a substrate of the SCF(FBXL2) complex. Interacts with PTPN13; dephosphorylates PIK3R2. Interacts with XBP1 isoform 2; the interaction is direct and induces translocation of XBP1 isoform 2 into the nucleus in a ER stress- and/or insulin-dependent but PI3K-independent manner. Interacts with PIK3R1; the interaction is dissociated in an insulin-dependent manner. Interacts with SRC.

Post-translational modifications. Phosphorylated in response to signaling from activated receptor-type protein kinases. Dephosphorylated by PTPRJ. Dephosphorylated at Tyr-655 by PTPN13. Phosphorylation of Tyr-655 impairs while its dephosphorylation promotes interaction with FBXL2 and SCF(FBXL2)-mediated polyubiquitination. Ubiquitinated. Polyubiquitination by the SCF(FBXL2) complex probably promotes proteasomal degradation of PIK3R2.

Disease relevance. Megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MPPH1) [MIM:603387] A syndrome characterized by megalencephaly, hydrocephalus, and polymicrogyria; polydactyly may also be seen. There is considerable phenotypic similarity between this disorder and the megalencephaly-capillary malformation syndrome. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The SH2 2 domain is required for interaction with FBXL2 and PTPN13.

Similarity. Belongs to the PI3K p85 subunit family.

RefSeq proteins (1): NP_005018* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000198	RhoGAP_dom	Domain
IPR000980	SH2	Domain
IPR001452	SH3_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR032498	PI3K_P85_iSH2	Domain
IPR035020	PI3kinase_P85_cSH2	Domain
IPR035022	PI3kinase_P85_nSH2	Domain
IPR035586	PI3K_p85beta_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily

Pfam: PF00017, PF00620, PF16454

Enzyme classification (BRENDA)

• EC 2.7.1.137 — phosphatidylinositol 3-kinase (BRENDA: 29 organisms, 131 substrates, 146 inhibitors, 16 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

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

UniProt features (61 total): helix 24, strand 11, sequence variant 6, domain 4, modified residue 3, mutagenesis site 3, turn 3, region of interest 3, compositionally biased region 2, chain 1, site 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
7RNU	nSH2 domain of p85-beta subunit of phosphatidylinositol 3-kinase in complex with an actin …	X-RAY DIFFRACTION	1.45
3O5Z	Crystal structure of the SH3 domain from p85beta subunit of phosphoinositide 3-kinase …	X-RAY DIFFRACTION	2.01
2XS6	CRYSTAL STRUCTURE OF THE RHOGAP DOMAIN OF HUMAN PIK3R2	X-RAY DIFFRACTION	2.09
6OX7	The complex of 1918 NS1-ED and the iSH2 domain of the human p85beta subunit of PI3K	X-RAY DIFFRACTION	2.75
6U28	Crystal structure of 1918 NS1-ED W187A in complex with the p85-beta-iSH2 domain of human …	X-RAY DIFFRACTION	2.95
7RCH	Crystal structure of NS1-ED of Vietnam influenza A virus in complex with the …	X-RAY DIFFRACTION	3.1
3MTT	Crystal structure of iSH2 domain of human p85beta, Northeast Structural Genomics …	X-RAY DIFFRACTION	3.3
2KT1	Solution NMR Structure of the SH3 Domain from the p85beta subunit of Phosphatidylinositol …	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00459-F1	82.53	0.43

Human Protein Atlas

Protein class: Metabolic proteins, Predicted intracellular proteins, Plasma proteins, RAS pathway related proteins, Cancer-related genes, Candidate cancer biomarkers, Disease related genes, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH approved · IF approved

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)

Position	Role
147	arginine finger; crucial for gtp hydrolysis by stabilizing the transition state

Post-translational modifications (3)

Type	Positions
Phosphotyrosine	464, 605, 655

Mutagenesis-validated functional residues (3)

Position	Phenotype
651	loss of interaction with fbxl2 and increased half-life; when associated with a-652.
652	loss of interaction with fbxl2 and increased half-life; when associated with a-651.
655	stabilized interaction with fbxl2 and decreased half-life.

Function

Pathways and Gene Ontology

Reactome pathways

43 curated (TAS) of 102; 12 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 102 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9725370	Signaling by ALK fusions and activated point mutants ⚕	curated
R-HSA-9842640	Signaling by LTK in cancer ⚕	curated
R-HSA-9673770	Signaling by PDGFRA extracellular domain mutants ⚕	curated
R-HSA-9673767	Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants ⚕	curated
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants ⚕	curated
R-HSA-389357	CD28 dependent PI3K/Akt signaling	curated
R-HSA-9013148	CDC42 GTPase cycle	curated
R-HSA-9927354	Co-stimulation by ICOS	curated
R-HSA-2424491	DAP12 signaling	curated
R-HSA-202424	Downstream TCR signaling	curated
R-HSA-186763	Downstream signal transduction	curated
R-HSA-9009391	Extra-nuclear estrogen signaling	curated
R-HSA-416476	G alpha (q) signalling events	curated
R-HSA-114604	GPVI-mediated activation cascade	curated
R-HSA-112399	IRS-mediated signalling	curated
R-HSA-912526	Interleukin receptor SHC signaling	curated
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling	curated
R-HSA-109704	PI3K Cascade	curated
R-HSA-198203	PI3K/AKT activation	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013404	RAC2 GTPase cycle	curated
R-HSA-9013423	RAC3 GTPase cycle	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-8853659	RET signaling	curated
R-HSA-8980692	RHOA GTPase cycle	curated
R-HSA-9013026	RHOB GTPase cycle	curated
R-HSA-9013405	RHOD GTPase cycle	curated
R-HSA-9035034	RHOF GTPase cycle	curated
R-HSA-9013409	RHOJ GTPase cycle	curated
R-HSA-9013420	RHOU GTPase cycle	curated
R-HSA-9696273	RND1 GTPase cycle	curated
R-HSA-9696270	RND2 GTPase cycle	curated
R-HSA-9696264	RND3 GTPase cycle	curated
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization	curated
R-HSA-2029485	Role of phospholipids in phagocytosis	curated
R-HSA-201556	Signaling by ALK	curated
R-HSA-9842663	Signaling by LTK	curated
R-HSA-1433557	Signaling by SCF-KIT	curated
R-HSA-1660499	Synthesis of PIPs at the plasma membrane	curated
R-HSA-210993	Tie2 Signaling	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-9700206	Signaling by ALK in cancer ⚕	—
R-HSA-9669938	Signaling by KIT in disease ⚕	—
R-HSA-9671555	Signaling by PDGFR in disease ⚕	—
R-HSA-1280218	Adaptive Immune System	—
R-HSA-422475	Axon guidance	—
R-HSA-202733	Cell surface interactions at the vascular wall	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-389356	Co-stimulation by CD28	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-2172127	DAP12 interactions	—
R-HSA-1266738	Developmental Biology	—
R-HSA-8939211	ESR-mediated signaling	—

MSigDB gene sets: 550 (showing top): REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_YELLOW_DN, REACTOME_SIGNALING_BY_INSULIN_RECEPTOR, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_ACTIN_FILAMENT_BUNDLE_ORGANIZATION, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_B_CELL_ACTIVATION, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOBP_RESPONSE_TO_ENDOPLASMIC_RETICULUM_STRESS, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT

GO Biological Process (14): intracellular glucose homeostasis (GO:0001678), immune response (GO:0006955), insulin receptor signaling pathway (GO:0008286), regulation of autophagy (GO:0010506), protein transport (GO:0015031), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), cellular response to insulin stimulus (GO:0032869), response to endoplasmic reticulum stress (GO:0034976), positive regulation of protein import into nucleus (GO:0042307), negative regulation of MAPK cascade (GO:0043409), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), positive regulation of transcription by RNA polymerase II (GO:0045944), signal transduction (GO:0007165)

GO Molecular Function (8): phosphotyrosine residue binding (GO:0001784), GTPase activator activity (GO:0005096), protein phosphatase binding (GO:0019903), receptor tyrosine kinase binding (GO:0030971), phosphatidylinositol 3-kinase regulatory subunit binding (GO:0036312), 1-phosphatidylinositol-3-kinase regulator activity (GO:0046935), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), cytosol (GO:0005829), focal adhesion (GO:0005925), phosphatidylinositol 3-kinase complex, class IA (GO:0005943)

Reactome top-level categories

20 top-level categories:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
IRS-mediated signalling	1
IRS-related events triggered by IGF1R	1
Insulin receptor signalling cascade	1
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
Signaling by Interleukins	1
PI Metabolism	1
Signaling by PDGF	1
Signaling by NTRK1 (TRKA)	1
TCR signaling	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell surface interactions at the vascular wall	1
PI3K/AKT Signaling in Cancer	1
DAP12 interactions	1
Fc epsilon receptor (FCERI) signaling	1
Cell-Cell communication	1
Co-stimulation by CD28	1
GPCR downstream signalling	1
Signaling by VEGF	1

GO top-level categories

51 GO namespaces:

Category	Terms
lymphocyte differentiation	2
glucose homeostasis	1
intracellular chemical homeostasis	1
immune system process	1
response to stimulus	1
cell surface receptor protein tyrosine kinase signaling pathway	1
cellular response to insulin stimulus	1
autophagy	1
regulation of catabolic process	1
transport	1
intracellular protein localization	1
establishment of protein localization	1
B cell activation	1
T cell activation	1
response to insulin	1
cellular response to peptide hormone stimulus	1
cellular response to stress	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
MAPK cascade	1
regulation of MAPK cascade	1
negative regulation of intracellular signal transduction	1
intracellular signaling cassette	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
protein phosphorylated amino acid binding	1
GTPase activity	1
enzyme activator activity	1
GTPase regulator activity	1
phosphatase binding	1
signaling receptor binding	1
protein tyrosine kinase binding	1
phosphatidylinositol 3-kinase binding	1
1-phosphatidylinositol-3-kinase activity	1
kinase regulator activity	1
protein dimerization activity	1
binding	1
intracellular membrane-bounded organelle	1
cytoplasm	1
cellular anatomical structure	1
cell-substrate junction	1
phosphatidylinositol 3-kinase complex, class I	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of MAPK cascade	BP	mutant phenotype
phosphatidylinositol 3-kinase/protein kinase B signal transduction	BP	direct assay
regulation of autophagy	BP	mutant phenotype
phosphotyrosine residue binding	MF	physical interaction
protein phosphatase binding	MF	physical interaction
receptor tyrosine kinase binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 1,774 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3R2	PIK3CA	P42336	830
PIK3R2	PIK3R3	Q92569	805
PIK3R2	PIK3CB	P42338	764
PIK3R2	PIK3CD	O00329	754
PIK3R2	PIK3R1	P27986	741
PIK3R2	SPRED1	Q7Z699	724
PIK3R2	PIK3R5	Q8WYR1	716
PIK3R2	USP8	P40818	702
PIK3R2	PIK3CG	P48736	691
PIK3R2	XBP1	P17861	646
PIK3R2	AKT1	P31749	642
PIK3R2	PIK3C3	Q8NEB9	640
PIK3R2	AKT3	Q9Y243	629
PIK3R2	PTEN	P60484	603
PIK3R2	MTOR	P42345	577

IntAct

Human interaction partners of PIK3R2 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 76 partners by confidence:

Partner	Interaction type	MIscore	Records
PIK3CA	association	0.900	42
PIK3CB	association	0.860	2
EGFR	physical association	0.760	4
NS	physical association	0.750	16
ERBB3	direct interaction	0.700	22
ERBB2	direct interaction	0.700	7
IKZF3	physical association	0.670	5
KRT38	physical association	0.670	5
MRFAP1L1	physical association	0.670	4
IRS4	association	0.640	3
CBL	physical association	0.620	2
PIK3R1	physical association	0.620	2
PDGFRB	association	0.610	2
KIT	association	0.590	19
IGF1R	physical association	0.590	2
INSR	proximity	0.570	1
NS1	association	0.560	9
DMWD	physical association	0.560	3
DYDC1	physical association	0.560	3
GOLGA2	physical association	0.560	3
KRT15	physical association	0.560	3
KRT20	physical association	0.560	3
RINT1	physical association	0.560	3
SPRED1	physical association	0.560	3
TRIM23	physical association	0.560	3
ARRB1	physical association	0.550	1
TGFBR2	association	0.530	3
PTGER3	association	0.530	2
RNF19B	association	0.530	1
CRK	physical association	0.490	2

BioGRID (348 interactions; top human partners by supporting records): EGFR (Two-hybrid; 10 records), PIK3R1 (Affinity Capture-MS; 9 records), CBL (Two-hybrid; 7 records), PIK3CB (Affinity Capture-MS; 7 records), PIK3CA (Affinity Capture-MS; 6 records), CRK (Two-hybrid; 4 records), ERBB2 (Reconstituted Complex; 4 records), ERBB3 (Affinity Capture-MS; 4 records), GRB2 (Two-hybrid; 4 records), IRS4 (Affinity Capture-MS; 4 records), PIK3R3 (Affinity Capture-MS; 4 records), TGFBR2 (Affinity Capture-MS; 4 records), CRKL (Far Western; 3 records), EFNB2 (Affinity Capture-MS; 3 records), FBXL2 (Affinity Capture-Western; 3 records)

SIGNOR signaling

12 signaling interactions:

A	Effect	B	Mechanism
CBL	down-regulates	PIK3R2	ubiquitination
ESR1	up-regulates	PIK3R2	binding
TGFBR2	up-regulates	PIK3R2	binding
TGFBR1	up-regulates	PIK3R2	binding
LAT	“up-regulates activity”	PIK3R2	binding
CBLB	“down-regulates activity”	PIK3R2	ubiquitination
FBXO2	“down-regulates quantity by destabilization”	PIK3R2	binding
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	PIK3R2	polyubiquitination
FBXL2	“down-regulates quantity by destabilization”	PIK3R2	binding
“Cullin 3-RBX1-Skp1”	“down-regulates quantity by destabilization”	PIK3R2	polyubiquitination
has-mir-126-3p	“down-regulates quantity by repression”	PIK3R2	“post transcriptional regulation”
EPHA2	up-regulates	PIK3R2

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ PIK3CA-PIK3R2 complex	2	PIK3CA, PIK3R2
★ PIK3CD-PIK3R2 complex	2	PIK3CD, PIK3R2

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
PI3K events in ERBB2 signaling	8	82.7×	1e-12
GAB1 signalosome	8	78.1×	2e-12
Constitutive Signaling by EGFRvIII	7	76.9×	9e-11
Signaling by ERBB2 ECD mutants	7	72.3×	1e-10
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	7	61.5×	4e-10
Signaling by ALK	7	61.5×	4e-10
Regulation of signaling by CBL	8	61.1×	2e-11
Downstream signal transduction	10	58.6×	6e-14

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of Rac protein signal transduction	5	47.0×	5e-06
epidermal growth factor receptor signaling pathway	13	46.7×	5e-16
insulin-like growth factor receptor signaling pathway	6	43.1×	6e-07
cell surface receptor protein tyrosine kinase signaling pathway	15	37.8×	5e-17
peptidyl-tyrosine phosphorylation	6	36.6×	1e-06
phosphatidylinositol 3-kinase/protein kinase B signal transduction	11	33.6×	6e-12
positive regulation of D-glucose import across plasma membrane	5	33.0×	2e-05
substrate adhesion-dependent cell spreading	6	29.9×	4e-06

Disease & clinical

Genetic variants

Variant evidence for PIK3R2: 535 ClinVar records (11 pathogenic / likely pathogenic); 5 ClinGen expert-panel interpretations; 3 CIViC cancer variants; 13 PharmGKB clinical annotations; 5 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	6
Uncertain significance	220
Likely benign	196
Benign	49

Top pathogenic / likely-pathogenic (11)

Showing all 11 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
39808	NM_005027.4(PIK3R2):c.1117G>A (p.Gly373Arg)	Pathogenic	reviewed by expert panel	28
280374	NM_005027.4(PIK3R2):c.1126A>G (p.Lys376Glu)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
280388	NM_005027.4(PIK3R2):c.1690A>G (p.Lys564Glu)	Pathogenic	criteria provided, single submitter	1
376165	NM_005027.4(PIK3R2):c.1681A>G (p.Asn561Asp)	Likely pathogenic	criteria provided, single submitter	1
431911	NM_005027.4(PIK3R2):c.1948A>G (p.Ser650Gly)	Likely pathogenic	criteria provided, single submitter	1
620407	NM_005027.4(PIK3R2):c.1359C>A (p.Tyr453Ter)	Likely pathogenic	criteria provided, single submitter	1
625283	NM_005027.4(PIK3R2):c.1056C>G (p.Phe352Leu)	Likely pathogenic	criteria provided, single submitter	1
976716	NM_005027.4(PIK3R2):c.988T>G (p.Trp330Gly)	Likely pathogenic	criteria provided, single submitter	1
143990	NM_005027.4(PIK3R2):c.1202T>C (p.Leu401Pro)	Pathogenic	no assertion criteria provided	1
995384	NM_005027.4(PIK3R2):c.1153G>A (p.Gly385Arg)	Pathogenic	no assertion criteria provided	1
800333	NM_005027.4(PIK3R2):c.850G>A (p.Val284Met)	Likely pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PIK3R2’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

ClinGen expert-panel interpretations (5)

Expert ACMG interpretations from Brain Malformations VCEP for overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes — a higher-authority tier than individual ClinVar submissions.

Assertion	Variants
Pathogenic	1
Likely Benign	3
Benign	1

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 28 predictions of 950):

Position(s)	Effect	Δscore	Sites
19:18153295	donor_loss	1.0000	2
19:18160469–18160470	acceptor_loss	1.0000	6
19:18160564–18160565	donor_loss	1.0000	2
19:18160917–18160918	acceptor_loss	1.0000	3
19:18161186–18161187	donor_loss	1.0000	3
19:18161964	acceptor_gain	1.0000
19:18161965	acceptor_loss	1.0000	3
19:18162052–18162053	donor_loss	1.0000	3
19:18162200–18162201	acceptor_loss	1.0000	3
19:18162406–18162407	acceptor_loss	1.0000	2

AlphaMissense

2,266 missense substitutions predicted likely pathogenic (of 4,685 scored), across 492 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M560	9	0.990	1.000
M476	9	0.963	0.999
H667	8	1.000	1.000
F389	8	0.999	1.000
F679	8	0.999	1.000
F644	8	0.998	1.000
H704	8	0.998	1.000
N414	8	0.997	1.000
F484	8	0.995	1.000
F491	8	0.995	1.000
D349	8	0.994	1.000
D557	8	0.993	0.999
D461	8	0.991	0.999
F352	8	0.990	1.000
N705	8	0.990	1.000
D346	8	0.989	0.999
N561	8	0.988	1.000
S649	8	0.987	0.998
D29	8	0.984	0.996
F70	8	0.983	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	2.27e-05

Disease associations

OMIM: gene MIM:603157 | disease phenotypes: MIM:603387, MIM:602501, MIM:254500

GenCC curated gene-disease

3 curated gene-disease records:

Disease	Classification	Inheritance	Records
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	Autosomal dominant
megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1	Definitive	Autosomal dominant	5
megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes	Definitive	AD

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (15 panels, 15 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

15 panels:

Panel	Rating
Cerebral malformation	green
DDG2P	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hydrocephalus	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Limb disorders	green
Malformations of cortical development	green
Neurological segmental overgrowth	green
Paediatric disorders	green
Segmental overgrowth disorders - Deep sequencing	green
Unexplained death in infancy and sudden unexplained death in childhood	green
Vascular skin disorders	green

Mondo (6): megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome 1 (MONDO:0011313), intellectual disability (MONDO:0001071), megalencephaly-capillary malformation-polymicrogyria syndrome (MONDO:0011240), megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (MONDO:0019375), overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes (MONDO:0100283), plasma cell myeloma (MONDO:0009693)

Orphanet (5): Megalencephaly-polymicrogyria-postaxial polydactyly-hydrocephalus syndrome (Orphanet:83473), Megalencephaly-capillary malformation-polymicrogyria syndrome (Orphanet:60040), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

38 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000238	Hydrocephalus
HP:0000256	Macrocephaly
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000506	Telecanthus
HP:0000508	Ptosis
HP:0000618	Blindness
HP:0000637	Long palpebral fissure
HP:0001090	Abnormally large globe
HP:0001162	Postaxial hand polydactyly
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001302	Pachygyria
HP:0001355	Megalencephaly
HP:0001548	Overgrowth
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001653	Mitral regurgitation
HP:0001671	Abnormal cardiac septum morphology
HP:0002007	Frontal bossing
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002187	Profound intellectual disability
HP:0002808	Kyphosis
HP:0002943	Thoracic scoliosis
HP:0003202	Skeletal muscle atrophy
HP:0005105	Abnormal nasal morphology
HP:0005280	Depressed nasal bridge
HP:0006380	Knee flexion contracture
HP:0007074	Thick corpus callosum
HP:0008936	Axial hypotonia
HP:0010775	Vascular ring
HP:0025352	Typically de novo
HP:0100259	Postaxial polydactyly
HP:0100542	Abnormal localization of kidney

GWAS associations

5 associations:

Study	Trait	p-value
GCST90002379_96	Basophil count	4e-13
GCST90002380_112	Basophil percentage of white cells	4e-12
GCST008550_17	Mental health study participation (completed survey)	1e-10
GCST008550_19	Mental health study participation (completed survey)	2e-9
GCST008550_18	Mental health study participation (completed survey)	3e-8

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0010130	health study participation
EFO:0005090	basophil count
EFO:0007992	basophil percentage of leukocytes

MeSH disease descriptors

4 disease descriptors:

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
C566381	Megalancephaly Polymicrogyria-Polydactyly Hydrocephalus Syndrome *(supp.)*
C536142	Megalencephaly cutis marmorata telangiectatica congenita *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3559703 (PROTEIN COMPLEX GROUP), CHEMBL3885615 (PROTEIN COMPLEX), CHEMBL4437 (SINGLE PROTEIN)

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes PIK3R2 — the drug acts on the assembly or class, not necessarily on this subunit alone.

26 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
BUPARLISIB	PI3-kinase class I	8	3
DACTOLISIB	PI3-kinase class I	8	3
GEDATOLISIB	PI3-kinase class I	8	3
TASELISIB	PI3-kinase class I	8	3
APITOLISIB	PI3-kinase class I	8	2
AZD-6482	PI3-kinase class I	8	2
BGT-226	PI3-kinase class I	8	2
IZORLISIB	PI3-kinase class I	8	2
OMIPALISIB	PI3-kinase class I	8	2
PANULISIB	PI3-kinase class I	8	2
PAXALISIB	PI3-kinase class I	8	2
PF-04691502	PI3-kinase class I	8	2
PICTILISIB	PI3-kinase class I	8	2
PILARALISIB	PI3-kinase class I	8	2
RECILISIB	PI3-kinase class I	8	2
SAMOTOLISIB	PI3-kinase class I	8	2
SF-1126	PI3-kinase class I	8	2
SONOLISIB	PI3-kinase class I	8	2
VOXTALISIB	PI3-kinase class I	8	2
ZSTK-474	PI3-kinase class I	8	2
DS-7423	PI3-kinase class I	8	1
GSK-1059615	PI3-kinase class I	8	1
PUQUITINIB MESYLATE DIHYDRATE	PI3-kinase class I	8	1
PWT-33587	PI3-kinase class I	8	1
VS-5584	PI3-kinase class I	8	1
WX-037	PI3-kinase class I	8	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 21,747 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

6 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL2216870	IDELALISIB	4	10,756
CHEMBL4650215	INAVOLISIB	4	937
CHEMBL2387080	TASELISIB	3	3,643
CHEMBL4438249	AMDIZALISIB	2	14
CHEMBL521851	PICTILISIB	2	6,322
CHEMBL3683575	ROGINOLISIB	2	75

Clinical evidence (CIViC)

Drug × variant × indication, from 2 curated evidence items; also 1 functional. CIViC evidence level: A (validated) → B (clinical) → C (case study) → D (preclinical) → E (inferential).

2 predictive associations by evidence level:

Variant	Therapy	Indication	Effect	Level	CIViC
BRAF V600E AND PIK3R2 N561D	Vemurafenib	Melanoma	Resistance	CIViC D	EID4783
PIK3R2 Overexpression	Vemurafenib	Melanoma	Resistance	CIViC D	EID6266

CIViC curated variants (3)

Named clinical variants curated in CIViC for this gene (the catalogue beneath the predictive evidence above):

N561D (missense variant), Overexpression, G373R.

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

13 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs117341846	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs117951771	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs118129530	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs138602176	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs145623321	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs148013902	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs148235907	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs150688309	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs55633228	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs56022120	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs58695150	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs79430272	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia
rs8110364	Toxicity	3	cyclophosphamide;epirubicin;fluorouracil	Breast Neoplasms;Neutropenia

PharmGKB variants

2 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8110364	PIK3R2	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil
rs58695150	MAST3, PIK3R2	3	0.00	1	cyclophosphamide;epirubicin;fluorouracil

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

13 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs8110364	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele A is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele G.	PMID:29593529
rs56022120	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs150688309	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele G is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs58695150	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs138602176	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele A is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele G.	PMID:29593529
rs148235907	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele A is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele G.	PMID:29593529
rs117951771	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs117341846	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs79430272	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs118129530	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele A is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele G.	PMID:29593529
rs145623321	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs148013902	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529
rs55633228	cyclophosphamide, epirubicin, fluorouracil	Toxicity	Allele T is associated with increased risk of Neutropenia due to cyclophosphamide, epirubicin and fluorouracil in women with Breast Neoplasms as compared to allele C.	PMID:29593529

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Binding affinities (BindingDB)

985 measured of 1634 human assays (1634 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2S)-2-[[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide	KI	0.04 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]butanamide	KI	0.048 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4S)-4-(fluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.051 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4S)-4-(difluoromethyl)-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.06 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclopropyl-2-[[2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.464 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-cyclobutyl-2-[[2-[(4R)-4-methyl-2-oxo-1,3-oxazolidin-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]acetamide	KI	0.949 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
Sapanisertib	IC50	1 nM	US-10172858: Combination pharmaceutical compositions and uses thereof
4-amino-6-[[(1S)-1-[3-chloro-6-(4-hydroxyphenyl)imidazo[1,2-b]pyridazin-7-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	1 nM	US-10208066: Imidazopyridazine compounds and their use
4-[3-(5,8-dichloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	1 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
2-amino-4-[[(S)-[3-(3-aminopropyl)-5-chloro-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]-6-methylpyrimidine-5-carbonitrile	IC50	1 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(1,3-thiazol-2-yl)benzimidazol-5-yl]morpholine	IC50	2 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-7-(1H-imidazol-5-yl)benzimidazol-5-yl]morpholine	IC50	2 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	2 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-difluoroquinolin-4-yl)-2-ethyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
5,8-difluoro-4-[6-(2-fluoro-4-pyridinyl)-2-methyl-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	2 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(1S)-1-[3-[2-aminoethyl(methyl)amino]-5-chloro-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	2 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	3 nM	US-10214519
4-[3-(8-chloroquinolin-4-yl)-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	3 nM	US-10214519
1-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-6-pyridin-4-ylbenzimidazole-4-carboxamide	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridin-2-amine	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-cyclopropyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-3-methylquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,7-difluoroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]pyridine-2-carbonitrile	IC50	3 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-propyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[3-[8-chloro-2-(difluoromethyl)quinolin-4-yl]-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-methyl-7-(4-methyl-1,3-thiazol-2-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[7-(2-chloro-1H-imidazol-5-yl)-3-(8-chloroquinolin-4-yl)-2-methylbenzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
4-[7-(2-chloro-1H-imidazol-5-yl)-3-(8-chloroquinolin-4-yl)benzimidazol-5-yl]morpholine	IC50	4 nM	US-10214519
8-chloro-5-fluoro-4-[2-methyl-6-pyridin-4-yl-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	4 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-2-propyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	4 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-dichloroquinolin-4-yl)-2-methyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	4 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
3-(3-aminopropyl)-5-chloro-2-[(S)-[(6-chloropyrido[3,2-d]pyrimidin-4-yl)amino]-cyclopropylmethyl]quinazolin-4-one	IC50	4 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(S)-[5-chloro-3-[3-(oxetan-3-ylamino)propyl]-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile	IC50	4 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(S)-[5-chloro-3-[3-[(4,4-difluorocyclohexyl)amino]propyl]-4-oxoquinazolin-2-yl]-cyclopropylmethyl]amino]pyrimidine-5-carbonitrile	IC50	4 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
4-[5-chloro-2-[(S)-cyclopropyl-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]methyl]-4-oxoquinazolin-3-yl]butanamide	IC50	4 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
2,4-diamino-6-[[(1S)-1-[5-chloro-3-(3-hydroxycyclobutyl)-4-oxoquinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	IC50	4 nM	US-11021467: Phosphatidylinositol 3-kinase inhibitors
4-[3-(8-chloroquinolin-4-yl)-2-ethyl-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-2-methyl-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1,3-oxazol-2-yl)-2-propylbenzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1,3-oxazol-2-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(8-chloro-5-fluoroquinolin-4-yl)-7-(2-chloro-1H-imidazol-5-yl)-2-methylbenzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-dichloro-2-methylquinolin-4-yl)-7-(1H-imidazol-5-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
4-[3-(5,8-difluoroquinolin-4-yl)-7-(1H-imidazol-5-yl)benzimidazol-5-yl]morpholine	IC50	5 nM	US-10214519
8-chloro-4-[6-pyridin-4-yl-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
8-chloro-4-[2-methyl-6-(2-methyl-4-pyridinyl)-4-(1H-1,2,4-triazol-5-yl)benzimidazol-1-yl]quinoline	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors
4-[3-(5,8-difluoroquinolin-4-yl)-2-propyl-7-(1H-1,2,4-triazol-5-yl)benzimidazol-5-yl]-3-fluoropyridin-2-amine	IC50	5 nM	US-10227350: Phosphatidylinositol 3-kinase inhibitors

ChEMBL bioactivities

1321 potent at pChembl≥5 of 1461 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL6002533
9.00	IC50	1	nM	CHEMBL5924262
9.00	IC50	1	nM	CHEMBL5916761
8.70	IC50	2	nM	CHEMBL5888916
8.70	IC50	2	nM	CHEMBL6033360
8.70	IC50	2	nM	CHEMBL5880970
8.70	IC50	2	nM	CHEMBL5902751
8.70	IC50	2	nM	CHEMBL5774157
8.70	IC50	2	nM	CHEMBL5957032
8.70	IC50	2	nM	CHEMBL4647791
8.70	IC50	2	nM	CHEMBL5818660
8.70	IC50	2	nM	CHEMBL5998780
8.70	IC50	2	nM	CHEMBL5924262
8.70	IC50	2	nM	CHEMBL5744071
8.52	IC50	3	nM	CHEMBL5769598
8.52	IC50	3	nM	CHEMBL4646376
8.52	IC50	3	nM	CHEMBL5897720
8.52	IC50	3	nM	CHEMBL5800580
8.52	IC50	3	nM	CHEMBL5964102
8.52	IC50	3	nM	CHEMBL4470860
8.52	IC50	3	nM	CHEMBL5921395
8.52	IC50	3	nM	CHEMBL5789334
8.52	IC50	3	nM	CHEMBL5993540
8.52	IC50	3	nM	CHEMBL5941074
8.40	IC50	4	nM	CHEMBL5789071
8.40	IC50	4	nM	CHEMBL5907233
8.40	IC50	4	nM	CHEMBL5780564
8.40	IC50	4	nM	CHEMBL5838167
8.40	IC50	4	nM	CHEMBL5999580
8.40	IC50	4	nM	CHEMBL5856108
8.40	IC50	4	nM	CHEMBL4647791
8.40	IC50	4	nM	CHEMBL5820221
8.40	IC50	4	nM	CHEMBL5756370
8.40	IC50	4	nM	CHEMBL5772820
8.40	IC50	4	nM	CHEMBL5961627
8.40	IC50	4	nM	CHEMBL5818660
8.40	IC50	4	nM	CHEMBL5941074
8.40	IC50	4	nM	CHEMBL5861950
8.40	IC50	4	nM	CHEMBL5816408
8.40	IC50	4	nM	CHEMBL5781665
8.40	IC50	4	nM	CHEMBL5888776
8.40	IC50	4	nM	CHEMBL5780265
8.30	IC50	5	nM	CHEMBL5771672
8.30	IC50	5	nM	CHEMBL5918117
8.30	IC50	5	nM	CHEMBL5853060
8.30	IC50	5	nM	CHEMBL5787062
8.30	IC50	5	nM	CHEMBL5849419
8.30	IC50	5	nM	CHEMBL5852093
8.30	IC50	5	nM	CHEMBL5957592
8.30	IC50	5	nM	CHEMBL5788149

PubChem BioAssay actives

7 with measured affinity, of 11 total; 6 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
[(1S,6Z,9S,9aS,10R,11aS)-6-[[3-(dimethylamino)propyl-methylamino]methylidene]-1-hydroxy-9-(methoxymethyl)-9a,11a-dimethyl-4,5,7-trioxo-1,2,3,3a,5a,9,10,11-octahydroindeno[4,5-h]isochromen-10-yl] acetate	1798030: PI3K Inhibition Assay from Article 10.1021/jm7012858: “Synthesis and structure-activity relationships of ring-opened 17-hydroxywortmannins: potent phosphoinositide 3-kinase inhibitors with improved properties and anticancer efficacy.”	ic50	0.0110	uM
2,4-diamino-6-[(6S)-6-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)-5-azaspiro[2.4]heptan-5-yl]pyrimidine-5-carbonitrile	1690218: Inhibition of human full-length recombinant His-tagged PI3K p110beta/p85beta expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay	ic50	0.1740	uM
4-[5-amino-6-(cyclopropanecarbonyl)pyrazin-2-yl]-N-(4-hydroxycyclohexyl)-3-methylbenzenesulfonamide	2066708: Inhibition of P13Kbeta (unknown origin) in the presence of ATP by scintillation proximity assay	ic50	0.4000	uM
N-[5-[4-[5-[[(2S,6R)-2,6-dimethylmorpholin-4-yl]methyl]-1,3-oxazol-2-yl]-1H-indazol-6-yl]-2-methoxy-3-pyridinyl]methanesulfonamide	1894037: Inhibition of human PI3K beta	ic50	0.6300	uM
4-[6-amino-5-(2-methyl-1,3-oxazol-5-yl)-3-pyridinyl]-N-(2-hydroxy-2-methylpropyl)-3-methylbenzenesulfonamide	2066708: Inhibition of P13Kbeta (unknown origin) in the presence of ATP by scintillation proximity assay	ic50	1.7000	uM
5-chloro-3-phenyl-2-[(6S)-5-(7H-purin-6-yl)-5-azaspiro[2.4]heptan-6-yl]quinazolin-4-one	1690218: Inhibition of human full-length recombinant His-tagged PI3K p110beta/p85beta expressed in baculovirus expression system using PIP2 as substrate measured after 2 hrs by ADP-Glo luminescence assay	ic50	2.6410	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, increases expression	3
Air Pollutants	increases abundance, increases oxidation, decreases expression, increases expression, affects cotreatment	3
bisphenol A	decreases expression, decreases methylation	2
Estradiol	decreases expression	2
Oxygen	decreases reaction, decreases expression, affects cotreatment, decreases phosphorylation	2
Ozone	affects cotreatment, increases oxidation, increases abundance, decreases expression	2
Smoke	decreases expression, increases abundance, increases expression	2
Valproic Acid	increases expression, increases methylation	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
nuciferine	affects cotreatment, decreases phosphorylation, decreases reaction	1
beta-lapachone	increases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
aflatoxin B2	increases methylation	1
muconaldehyde	decreases expression	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
antimonite	decreases expression, increases abundance	1
chloropicrin	decreases expression	1
monomethylarsonous acid	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	affects cotreatment, increases expression	1

ChEMBL screening assays

27 unique, capped per target: 27 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3706369	Binding	Binding Assay: The efficacy of compounds of the invention in inhibiting the PI3K induced-lipid phosphorylation may be tested in the following binding assay. The assay combines the scintillation proximity assay technology (SPA, Amersham) wit	Tricyclic pyrazol amine derivatives

Cellosaurus cell lines

19 cell lines: 10 cancer cell line, 7 induced pluripotent stem cell, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DV	Abcam HEK293T PIK3R2 KO	Transformed cell line	Female
CVCL_B8ML	Abcam HCT 116 PIK3R2 KO	Cancer cell line	Male
CVCL_B9AC	Abcam MCF-7 PIK3R2 KO	Cancer cell line	Female
CVCL_B9PT	Abcam A-549 PIK3R2 KO	Cancer cell line	Male
CVCL_D0WN	HPS2936	Induced pluripotent stem cell	Female
CVCL_D0WP	HPS2937	Induced pluripotent stem cell	Female
CVCL_D0WQ	HPS2938	Induced pluripotent stem cell	Female
CVCL_D0WR	HPS2939	Induced pluripotent stem cell	Female
CVCL_D0WS	HPS2940	Induced pluripotent stem cell	Female
CVCL_D0WT	HPS2941	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT05657860	Phase 4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	Phase 4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	Phase 4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	Phase 4	RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	Phase 4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	Phase 4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	Phase 4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	Phase 4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	Phase 4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	Phase 4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	Phase 4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	Phase 4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	Phase 4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	Phase 4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	Phase 4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	Phase 4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	Phase 4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	Phase 4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	Phase 4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	Phase 4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	Phase 4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	Phase 4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	Phase 4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	Phase 4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	Phase 4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	Phase 4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	Phase 4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	Phase 4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	Phase 4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	Phase 4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	Phase 4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	Phase 4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	Phase 4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	Phase 4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	Phase 4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	Phase 4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	Phase 4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	Phase 4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	Phase 4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	Phase 4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	Phase 4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	Phase 4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	Phase 4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting
NCT06409702	Phase 4	RECRUITING	Treatment of High-risk Newly Diagnosed Multiple Myeloma With Minimal Residual Disease Detection
NCT06425276	Phase 4	COMPLETED	Evaluate Safety and Efficacy of High-dose Melphalan HCL for Injection in MM Patients With Auto-HSC Transplantation
NCT07030517	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Assess Safety of Teclistamab in Indian Participants With Relapsed and Refractory Multiple Myeloma
NCT07094048	Phase 4	RECRUITING	Immunoglobulins in Multiple Myeloma Patients Receiving a BCMA-Directed T Cell Engager
NCT07101445	Phase 4	RECRUITING	Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial
NCT07154537	Phase 4	ACTIVE_NOT_RECRUITING	Pneumococcal Conjugated Vaccine 13 (PCV13) for Patients With Multiple Myeloma (MM)
NCT07334535	Phase 4	NOT_YET_RECRUITING	Isa-VRD in TIE HRMM
NCT07474961	Phase 4	NOT_YET_RECRUITING	BLOOD-dose: A Platform Trial Evaluating Dose Optimization in Hematological Diseases.
NCT02270736	Phase 3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT00001561	Phase 3	COMPLETED	Active Immunization of Sibling Bone Marrow Transplant Donors Against Purified Myeloma Protein of the Recipient Undergoing Allogeneic Bone Marrow Transplantation
NCT00002548	Phase 3	COMPLETED	SWOG-9321 Melphalan, TBI, and Transplant vs Combo Chemo in Untreated Myeloma
NCT00002556	Phase 3	COMPLETED	Combination Chemotherapy With or Without High Dose Cyclophosphamide and Recombinant Interferon Alfa-2b in Treating Patients With Previously Untreated Stage I-III Multiple Myeloma
NCT00002850	Phase 3	COMPLETED	Antibiotic Therapy in Preventing Early Infection in Patients With Multiple Myeloma Who Are Receiving Chemotherapy
NCT00005834	Phase 3	TERMINATED	S9922 Combination Chemo Plus Filgrastim With or Without Thalidomide in Refractory Multiple Myeloma
NCT00037791	Phase 3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00038233	Phase 3	COMPLETED	Thalidomide for Multiple Myeloma

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PIK3R2 across ~30M SureChEMBL compounds — explore on Sugi Predict.