PIK3CD

Summary

PIK3CD (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta, HGNC:8977) is a protein-coding gene on chromosome 1p36.22, encoding Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform (O00329). Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides.

Phosphoinositide 3-kinases (PI3Ks) phosphorylate inositol lipids and are involved in the immune response. The protein encoded by this gene is a class I PI3K found primarily in leukocytes. Like other class I PI3Ks (p110-alpha p110-beta, and p110-gamma), the encoded protein binds p85 adapter proteins and GTP-bound RAS. However, unlike the other class I PI3Ks, this protein phosphorylates itself, not p85 protein.

Source: NCBI Gene 5293 — RefSeq curated summary.

At a glance

• Gene–disease (curated): immunodeficiency 14b, autosomal recessive (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 9
• Clinical variants (ClinVar): 944 total — 19 pathogenic, 14 likely-pathogenic
• Phenotypes (HPO): 142
• Druggable target: yes — 66 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005026

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8977
Approved symbol	PIK3CD
Name	phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	p110D
Ensembl gene	ENSG00000171608
Ensembl biotype	protein_coding
OMIM	602839
Entrez	5293

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 24 protein_coding, 9 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000361110, ENST00000377346, ENST00000479223, ENST00000481137, ENST00000484851, ENST00000698706, ENST00000698707, ENST00000698708, ENST00000698709, ENST00000698710, ENST00000698711, ENST00000698712, ENST00000698713, ENST00000698714, ENST00000698715, ENST00000698716, ENST00000698717, ENST00000698718, ENST00000698719, ENST00000698786, ENST00000698787, ENST00000698788, ENST00000698789, ENST00000892287, ENST00000892288, ENST00000892289, ENST00000892290, ENST00000932635, ENST00000932636, ENST00000932637, ENST00000932638, ENST00000932639, ENST00000960479, ENST00000960480, ENST00000960481, ENST00000960482

RefSeq mRNA: 3 — MANE Select: NM_005026 NM_001350234, NM_001350235, NM_005026

CCDS: CCDS104, CCDS90856

Canonical transcript exons

ENST00000377346 — 24 exons

Exon	Start	End
ENSE00001149505	9720112	9720242
ENSE00001149519	9724804	9724936
ENSE00001149532	9724276	9724421
ENSE00001149551	9723125	9723292
ENSE00001149563	9722528	9722606
ENSE00001149574	9722244	9722356
ENSE00001149616	9719921	9720017
ENSE00001149626	9718694	9718915
ENSE00001149633	9717537	9717626
ENSE00001149654	9716440	9716619
ENSE00001149661	9715849	9716078
ENSE00001180741	9721975	9722153
ENSE00001180748	9721761	9721860
ENSE00001180753	9721444	9721587
ENSE00001180759	9721127	9721248
ENSE00001284058	9720742	9720909
ENSE00001298047	9720611	9720661
ENSE00001643426	9723969	9724092
ENSE00001879105	9715541	9715769
ENSE00002225148	9726909	9729114
ENSE00003550926	9716959	9717108
ENSE00003974493	9691467	9691571
ENSE00003974496	9651731	9651802
ENSE00003974501	9710424	9710596

Expression profiles

Bgee: expression breadth ubiquitous, 253 present calls, max score 97.96.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6697 / max 892.4409, expressed in 1672 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
529	16.8188	819
533	3.7718	1325
530	1.0614	270
532	0.4771	234
534	0.2434	111
536	0.2154	66
201347	0.0818	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.96	gold quality
blood	UBERON:0000178	97.31	gold quality
lymph node	UBERON:0000029	94.11	gold quality
leukocyte	CL:0000738	93.94	gold quality
mononuclear cell	CL:0000842	93.63	gold quality
trabecular bone tissue	UBERON:0002483	93.63	gold quality
spleen	UBERON:0002106	93.56	gold quality
monocyte	CL:0000576	93.52	gold quality
vermiform appendix	UBERON:0001154	93.49	gold quality
bone marrow cell	CL:0002092	92.76	gold quality
bone marrow	UBERON:0002371	90.87	gold quality
periodontal ligament	UBERON:0008266	90.70	gold quality
caecum	UBERON:0001153	90.67	gold quality
paraflocculus	UBERON:0005351	87.99	silver quality
thymus	UBERON:0002370	87.84	gold quality
frontal pole	UBERON:0002795	87.84	silver quality
epithelium of nasopharynx	UBERON:0001951	87.20	gold quality
parietal pleura	UBERON:0002400	87.04	gold quality
ileal mucosa	UBERON:0000331	86.61	gold quality
amniotic fluid	UBERON:0000173	86.20	gold quality
tibia	UBERON:0000979	86.19	gold quality
middle frontal gyrus	UBERON:0002702	86.03	gold quality
gluteal muscle	UBERON:0002000	85.91	gold quality
triceps brachii	UBERON:0001509	85.69	gold quality
pleura	UBERON:0000977	85.30	gold quality
tonsil	UBERON:0002372	85.19	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.99	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.74	gold quality
cartilage tissue	UBERON:0002418	82.93	gold quality
decidua	UBERON:0002450	82.53	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	11.13
E-ANND-3	yes	5.75

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RUNX1

miRNA regulators (miRDB)

73 targeting PIK3CD, 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-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-5692A	100.00	74.40	6850
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
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-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3682-5P	99.93	67.97	1163
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-320A-3P	99.77	69.73	2107
HSA-MIR-320B	99.77	69.73	2107
HSA-MIR-320C	99.77	69.73	2107
HSA-MIR-320D	99.77	69.73	2107
HSA-MIR-4429	99.77	69.62	2111
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-5197-5P	99.64	69.08	1494

Literature-anchored findings (GeneRIF, showing 40)

• PI3K delta can play a selective role in the amplification of phosphatidylinositol (3,4,5) trisphosphate (PIP3) levels that lead to neutrophil polarization and regulate directional migration, but not random locomotion. (PMID:12594293)
• p110delta isoform of PI3K is consistently expressed at a high level in blast cells from AML, in contrast to the other class I isoforms (PMID:15840695)
• Stimulation of TNF-alpha-primed human neutrophils with fMLP results in biphasic activation of PI3K; the first phase is largely dependent on PI3Kgamma; the second phase is largely dependent on PI3Kdelta and regulates parallel activation of ROS production (PMID:15878979)
• p110beta, -gamma, and -delta isoforms of class I phosphoinositide 3-kinase have roles in oncogenic transformation (PMID:16432180)
• These findings could shed light on further understanding the polymorphisms of p110delta in B-cell immunodeficiency and different populations. (PMID:16984281)
• p110delta contributes significantly to Th cell expansion and differentiation in vitro and in vivo, also in the context of CD28 costimulation. (PMID:17015696)
• This review describes the second-messenger PI3K delta signalling pathways that are involved in immune responses relevant to the pathogenesis of rheumatoid arthritis and other inflammatory diseases. (PMID:17290298)
• identifies the RhoA/ROCK pathway as a major target of p110delta-mediated PI3K signalling (PMID:17581634)
• novel function of the class I(A) PI3K isoform p110delta in neuroblastoma growth and survival. (PMID:18281552)
• These results demonstrate that CD148 may interact with and dephosphorylate p85 when it is phosphorylated and modulate the magnitude of phosphoinositide 3-kinase activity. (PMID:18348712)
• In contrast with PI3Kalpha, beta and gamma, PI3Kdelta accounts for most of the PI3K-dependent signaling ruling the production of IL-1beta, IL-6, TNF and sIL-1Ra in monocytes. (PMID:18471882)
• Results identify a conserved phosphoinositide 3-kinase p11delta promoter region that may account for the predominant leukocyte expression of p110delta. (PMID:19357769)
• RUNX1 may play a critical role in chemotherapy response in acute megakaryocytic leukemia by regulating the PI3-kinase/Akt pathway. (PMID:19638627)
• These studies establish that previously activated memory T cells are at least as sensitive to p110delta inhibition as naive T cells and show that mouse models accurately predict p110delta function in human T cells. (PMID:20081091)
• Data show that similar responses were seen in cancer cells with wild-type or activated mutant PI3K genes treated with p110alpha/delta or p110alpha/beta/delta inhibitors in cell viability assays. (PMID:20103642)
• PI3Kdelta expression and signaling is increased in the lungs of patients with COPD. (PMID:20381852)
• IFN-beta triggers an atypical MEK2/PI3Kdelta signaling cascade to regulate sIL-1Ra expression in monocytes. (PMID:20837746)
• These observations suggest that PI3Kdelta contributes to induction of enhanced systemic lupus erythematosus memory T cell survival (PMID:21810603)
• PI3K p110delta is important for TGFB1 induced production of the contractile proteins calponin and alpha-SMA and the proinflammatory cytokine IL-6 (PMID:22015454)
• p37delta appears to be a new tumor-specific isoform of p110delta with growth-promoting properties (PMID:22020336)
• Isoform specific targeting of PI3Kdelta may be beneficial in the treatment of glioblastoma multiforme by specifically inhibiting tumour cell migration capacity. (PMID:22079609)
• p110delta-dependent translocation of exogenous CSF-1 to the nucleus-associated CSF-1Rs, correlating with a prominent role of p110delta in activation of the Rab5 GTPase, a key regulator of endocytic trafficking (PMID:22084313)
• Findings suggest that excessive PI3Kdelta activity is characteristic in Hodgkin lymphoma (HL) and support clinical evaluation of GS-1101, alone and in combination, as targeted therapy for HL. (PMID:22210877)
• present a detailed biochemical and bioinformatic characterization of p110delta gene regulation, demonstrating that PIK3CD has distinct promoters, some of which can be dynamically activated by pro-inflammatory mediators (PMID:22375552)
• PI3 kinase delta is a key regulator of synoviocyte function in rheumatoid arthritis. (PMID:22433439)
• PIK3CD shows evidence of association with schizophrenia, and is a previously undescribed therapeutic target for the treatment of psychiatric disorders. (PMID:22689948)
• Studies indicate that the research with phosphoinositide 3-kinase p110-delta (p110delta) in chronic lymphocytic leukemia (CLL) have led to a more fundamental understanding of CLL signaling defects. (PMID:22711705)
• High PIK3CA/PIK3CD ratio identified a subset of primary mantle cell lymphomas resistant to GS-1101 and this ratio increased significantly with relapse. (PMID:23341541)
• The expression of PIK3CD is inversely correlated with miR-30a levels in metastatic colorectal carcinoma tissues. (PMID:23486085)
• These results suggest that PI3Kdelta mediates dsRNA-induced upregulation of B7-H1 without affecting the activation of NF-kappaB. (PMID:23660190)
• this study found E1021K in 17 patients with activated PI3K-delta syndrome (APDS), from seven unrelated families with, but not among 3346 healthy subjects. (PMID:24136356)
• Data indicate that patients with combined immunodeficiency disease who share gain-of-function mutations in PIK3CD (p110delta), resulting in hyperactivation of mTOR signaling and skewed the differentiation of CD8+ T cells. (PMID:24165795)
• Study reveals functional and mechanistic links between miRNA-30b and oncogene KRAS, PIK3CD and BCL2 in the pathogenesis of colorectal carcinoma. (PMID:24293274)
• PI3Kdelta contributes to multiple aspects of the pathogenic FLS behavior in RA. These observations, together with previous findings that PI3Kdelta regulates FLS growth and survival (PMID:24470496)
• PIK3CD is a target gene of miR-125b in Ewing’s sarcoma cells. RT-PCR and western blot assays identify over-expression of miR-125b that suppresses the expression of PIK3CD mRNA and protein. (PMID:24517182)
• PIK3CD was inversely correlated with miR-663 in glioblastoma specimens and predicted poor prognosis of patients with glioblastoma (PMID:24523440)
• Gestational diabetes mellitus is accompanied by leukocyte PIK3CD overexpression associated with reduced plasma LDL-C and TC levels, as well as with hyperglycaemia and elevated leukocyte SIRT1 mRNA. (PMID:24549598)
• PI3K p110delta uniquely promotes gain-of-function Shp2-induced GM-CSF hypersensitivity in a model of juvenile myelomonocytic leukemia. (PMID:24553178)
• Mutations in PIK3CD can cause hyper IgM syndrome (HIGM) associated with increased cancer susceptibility. (PMID:24610295)
• The p110delta PI3K-selective compound CAL-101 (Idelalisib) did not inhibit markers of PI3K activity in cancer or stromal cells. (PMID:24648465)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3cd	ENSDARG00000003250
mus_musculus	Pik3cd	ENSMUSG00000039936
rattus_norvegicus	Pik3cd	ENSRNOG00000016846
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), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PI4KB (ENSG00000143393), PI4KA (ENSG00000241973)

Protein

Protein identifiers

Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform — O00329 (reviewed: O00329)

Alternative names: Phosphatidylinositol 4,5-bisphosphate 3-kinase 110 kDa catalytic subunit delta

All UniProt accessions (9): A0A2K8FKV1, A0A8V8TM62, A0A8V8TML5, A0A8V8TMM0, A0A8V8TNP1, A0A8V8TNW9, B7ZM44, O00329, F8W9P4

UniProt curated annotations — full annotation on UniProt →

Function. Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. Uses ATP and 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. Mediates immune responses. Plays a role in B-cell development, proliferation, migration, and function. Required for B-cell receptor (BCR) signaling. Mediates B-cell proliferation response to anti-IgM, anti-CD40 and IL4 stimulation. Promotes cytokine production in response to TLR4 and TLR9. Required for antibody class switch mediated by TLR9. Involved in the antigen presentation function of B-cells. Involved in B-cell chemotaxis in response to CXCL13 and sphingosine 1-phosphate (S1P). Required for proliferation, signaling and cytokine production of naive, effector and memory T-cells. Required for T-cell receptor (TCR) signaling. Mediates TCR signaling events at the immune synapse. Activation by TCR leads to antigen-dependent memory T-cell migration and retention to antigenic tissues. Together with PIK3CG participates in T-cell development. Contributes to T-helper cell expansion and differentiation. Required for T-cell migration mediated by homing receptors SELL/CD62L, CCR7 and S1PR1 and antigen dependent recruitment of T-cells. Together with PIK3CG is involved in natural killer (NK) cell development and migration towards the sites of inflammation. Participates in NK cell receptor activation. Plays a role in NK cell maturation and cytokine production. Together with PIK3CG is involved in neutrophil chemotaxis and extravasation. Together with PIK3CG participates in neutrophil respiratory burst. Plays important roles in mast-cell development and mast cell mediated allergic response. Involved in stem cell factor (SCF)-mediated proliferation, adhesion and migration. Required for allergen-IgE-induced degranulation and cytokine release. The lipid kinase activity is required for its biological function. Isoform 2 may be involved in stabilizing total RAS levels, resulting in increased ERK phosphorylation and increased PI3K activity.

Subunit / interactions. Heterodimer of a catalytic subunit PIK3CD and a p85 regulatory subunit (PIK3R1, PIK3R2 or PIK3R3). Interacts with ERAS. Interacts with HRAS.

Subcellular location. Cytoplasm.

Tissue specificity. In humans, the highest levels of expression are seen in peripheral blood mononuclear cells, spleen, and thymus, and low levels of expression in testes, uterus, colon, and small intestine but not in other tissues examined including prostate, heart, brain, and liver. Isoform 2 is expressed in normal thymus, lung and spleen tissues, and is detected at low levels in normal lysates from colon and ovarian biopsies, at elevated levels in lysates from colorectal tumors and is abundantly expressed in some ovarian tumors (at protein level). Both isoform 1 and isoform 2 are widely expressed. Isoform 1 is expressed predominantly in leukocytes.

Post-translational modifications. Autophosphorylation on Ser-1039 results in the almost complete inactivation of the lipid kinase activity.

Disease relevance. Immunodeficiency 14A with lymphoproliferation, autosomal dominant (IMD14A) [MIM:615513] A disorder characterized by recurrent respiratory infections, progressive airway damage, lymphopenia, increased circulating transitional B cells, increased immunoglobulin M, reduced immunoglobulin G2 levels in serum, and impaired vaccine responses. The disease is caused by variants affecting the gene represented in this entry. Immunodeficiency 14B, autosomal recessive (IMD14B) [MIM:619281] An autosomal recessive, primary immunodeficiency characterized by recurrent sinopulmonary infections apparent in early childhood. Some patients may develop inflammatory bowel disease or osteomyelitis. Immunological features include hypogammaglobulinemia, decreased levels of B cells, and evidence of impaired immune-mediated cytotoxicity and defective T-cell function. The disease is caused by variants affecting the gene represented in this entry. Roifman-Chitayat syndrome (ROCHIS) [MIM:613328] An autosomal recessive digenic disorder characterized by global developmental delay, variable neurologic features such as seizures and ataxia, optic atrophy, dysmorphic facial features, distal skeletal anomalies, and recurrent invasive infections due to combined immunodeficiency. The disease is caused by variants affecting distinct genetic loci, including the gene represented in this entry. Caused by the simultaneous occurrence of homozygous mutations in PIK3CD and KNSTRN.

Activity regulation. Activated by growth factors and cytokine receptors through a tyrosine-kinase-dependent mechanism. Activated by RAS. IC87114 inhibits lipid kinase activity and is selective in cells at doses up to 5-10 uM. IC87114 blocks T-cell receptor signaling in naive and memory T-cells and reduces cytokine production by memory T-cells.

Pathway. Phospholipid metabolism; phosphatidylinositol phosphate biosynthesis.

Miscellaneous. IC87114 inhibitor reduces passive cutaneous anaphylaxis, attenuates allergic airway inflammation and hyperresponsiveness and allergen induced rhinitis response. Inhibitors may have therapeutic potential for the treatment of immune system-mediated diseases such as auto-immune diseases, inflammation and allergy.

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

Isoforms (2)

UniProt ID	Names	Canonical?
O00329-1	1, p110-delta	yes
O00329-2	2, p37-delta

RefSeq proteins (3): NP_001337163, NP_001337164, NP_005017* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000341	PI3K_Ras-bd_dom	Domain
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR001263	PI3K_accessory_dom	Domain
IPR002420	PI3K-type_C2_dom	Domain
IPR003113	PI3K_ABD	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
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR037703	PI3-kinase_delta_cat	Domain
IPR042236	PI3K_accessory_sf	Homologous_superfamily

Pfam: PF00454, PF00613, PF00792, PF00794, PF02192

Enzyme classification (BRENDA):

• EC 2.7.1.137 — phosphatidylinositol 3-kinase (BRENDA: 29 organisms, 131 substrates, 146 inhibitors, 16 Km, 0 kcat entries)
• EC 2.7.1.153 — phosphatidylinositol-4,5-bisphosphate 3-kinase (BRENDA: 12 organisms, 48 substrates, 96 inhibitors, 1 Km, 0 kcat entries)
• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

14 substrates with measured Km, best-characterized 14. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
ATP	0.03–44	7
PHOSPHATIDYLINOSITOL	0.034–64	3
KKRAARATSNVFA	0.013–0.045	3
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE	0.004–15	2
PHOSPHATIDYLINOSITOL 4-PHOSPHATE	0.009–10	2
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
1,2-DIOCTANOYLPHOSPHATIDYLINOSITOL 4,5-DIPHOSPHA	0.05	1
PHOSPHATIDYLINOSITOL-4,5-BISPHOSPHATE	0.011	1
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 3 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-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+) (RHEA:21292)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H(+) (RHEA:43396)

UniProt features (112 total): helix 45, strand 39, turn 8, domain 5, region of interest 4, mutagenesis site 3, modified residue 2, splice variant 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
6PYR	X-RAY DIFFRACTION	2.21
8S3R	X-RAY DIFFRACTION	2.28
7JIS	X-RAY DIFFRACTION	2.42
8BCY	X-RAY DIFFRACTION	2.43
9L3R	X-RAY DIFFRACTION	2.5
6PYU	X-RAY DIFFRACTION	2.54
6OCO	X-RAY DIFFRACTION	2.58
5DXU	X-RAY DIFFRACTION	2.64
6G6W	X-RAY DIFFRACTION	2.72
6OCU	X-RAY DIFFRACTION	2.77
7LM2	X-RAY DIFFRACTION	2.79
5VLR	X-RAY DIFFRACTION	2.8
9GDI	X-RAY DIFFRACTION	2.81
5UBT	X-RAY DIFFRACTION	2.83
5M6U	X-RAY DIFFRACTION	2.85
9GCF	X-RAY DIFFRACTION	2.89
5T8F	X-RAY DIFFRACTION	2.91
7LQ1	X-RAY DIFFRACTION	2.96

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00329-F1	88.21	0.69

Functional residue map

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

Post-translational modifications (2): 524, 1039

Mutagenesis-validated functional residues (3):

Position	Phenotype
894	abolishes lipid and protein kinase activities.
1039	abolishes autophosphorylation, no effect on lipid kinase activity.
1039	abolishes autophosphorylation, reduced lipid kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-512988	Interleukin-3, Interleukin-5 and GM-CSF signaling
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8853659	RET signaling
R-HSA-9027276	Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-912526	Interleukin receptor SHC signaling
R-HSA-912631	Regulation of signaling by CBL
R-HSA-9680350	Signaling by CSF1 (M-CSF) in myeloid cells
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9927354	Co-stimulation by ICOS

MSigDB gene sets: 914 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INTERLEUKIN_2_FAMILY_SIGNALING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_NATURAL_KILLER_CELL_DIFFERENTIATION, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VASCULAR_ENDOTHELIAL_GROWTH_FACTOR_SIGNALING_PATHWAY, GOBP_MYELOID_CELL_HOMEOSTASIS, PAX4_01, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS

GO Biological Process (48): natural killer cell differentiation (GO:0001779), positive regulation of cytokine production (GO:0001819), positive regulation of endothelial cell proliferation (GO:0001938), adaptive immune response (GO:0002250), mast cell chemotaxis (GO:0002551), respiratory burst involved in defense response (GO:0002679), protein phosphorylation (GO:0006468), inflammatory response (GO:0006954), immune response (GO:0006955), signal transduction (GO:0007165), positive regulation of endothelial cell migration (GO:0010595), positive regulation of gene expression (GO:0010628), T cell chemotaxis (GO:0010818), cell migration (GO:0016477), natural killer cell activation (GO:0030101), B cell differentiation (GO:0030183), T cell differentiation (GO:0030217), positive regulation of cell migration (GO:0030335), neutrophil chemotaxis (GO:0030593), T cell costimulation (GO:0031295), positive regulation of neutrophil apoptotic process (GO:0033031), natural killer cell chemotaxis (GO:0035747), B cell chemotaxis (GO:0035754), phosphatidylinositol-3-phosphate biosynthetic process (GO:0036092), vascular endothelial growth factor signaling pathway (GO:0038084), T cell activation (GO:0042110), B cell activation (GO:0042113), mast cell degranulation (GO:0043303), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), innate immune response (GO:0045087), positive regulation of angiogenesis (GO:0045766), phosphatidylinositol-mediated signaling (GO:0048015), T cell receptor signaling pathway (GO:0050852), B cell receptor signaling pathway (GO:0050853), mast cell differentiation (GO:0060374), neutrophil extravasation (GO:0072672), positive regulation of epithelial tube formation (GO:1905278), immune system process (GO:0002376), leukocyte mediated immunity (GO:0002443), lipid metabolic process (GO:0006629)

GO Molecular Function (8): ATP binding (GO:0005524), 1-phosphatidylinositol-3-kinase activity (GO:0016303), 1-phosphatidylinositol-4-phosphate 3-kinase activity (GO:0035005), 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity (GO:0046934), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (5): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), phosphatidylinositol 3-kinase complex (GO:0005942), phosphatidylinositol 3-kinase complex, class IA (GO:0005943)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
Interleukin-3, Interleukin-5 and GM-CSF signaling	2
Intracellular signaling by second messengers	1
PI Metabolism	1
PI3K/AKT Signaling in Cancer	1
Co-stimulation by CD28	1
Signaling by Interleukins	1
Negative regulation of the PI3K/AKT network	1
Axon guidance	1
Signaling by Erythropoietin	1
Interleukin-2 family signaling	1
Cytokine Signaling in Immune system	1
Signaling by the B Cell Receptor (BCR)	1
Response of endothelial cells to shear stress	1
Regulation of T cell activation by CD28 family	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lymphocyte differentiation	3
phosphatidylinositol kinase activity	3
defense response	2
cellular anatomical structure	2
natural killer cell activation	1
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
immune response	1
leukocyte chemotaxis	1
mast cell migration	1
immune effector process	1
respiratory burst	1
phosphorylation	1
protein modification process	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
regulation of endothelial cell migration	1
positive regulation of cell migration	1
endothelial cell migration	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
lymphocyte chemotaxis	1
T cell migration	1
cell motility	1
lymphocyte activation	1
B cell activation	1
T cell activation	1
cell migration	1
regulation of cell migration	1

Protein interactions and networks

STRING

1986 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3CD	PIK3R2	O00459	997
PIK3CD	PIK3R3	Q92569	997
PIK3CD	PIK3R1	P27986	996
PIK3CD	PIK3R5	Q8WYR1	990
PIK3CD	PIK3CA	P42336	983
PIK3CD	PIK3CB	P42338	983
PIK3CD	ARHGEF7	Q14155	955
PIK3CD	PIK3CG	P48736	923
PIK3CD	PPP1R12C	Q9BZL4	822
PIK3CD	IMMT	Q16891	803
PIK3CD	BTK	Q06187	770
PIK3CD	SYK	P43405	758
PIK3CD	AKT1	P31749	757
PIK3CD	PI3	P19957	752
PIK3CD	PLCG2	P16885	743

IntAct

40 interactions, top by confidence:

A	B	Type	Score
PIK3R1	PIK3CD	psi-mi:“MI:0407”(direct interaction)	0.890
PIK3R1	PIK3CD	psi-mi:“MI:0915”(physical association)	0.890
PIK3CD	PIK3R1	psi-mi:“MI:0915”(physical association)	0.890
PIK3R1	PIK3CD	psi-mi:“MI:0914”(association)	0.890
PIK3R1	PIK3CD	psi-mi:“MI:0403”(colocalization)	0.890
PIK3R3	PIK3CD	psi-mi:“MI:0914”(association)	0.800
PIK3CD	PIK3R3	psi-mi:“MI:0915”(physical association)	0.800
PIK3CD	PIK3R1	psi-mi:“MI:0915”(physical association)	0.560
	PIK3CD	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
PIK3CD		psi-mi:“MI:0915”(physical association)	0.400
PIK3R1	PIK3CD	psi-mi:“MI:0915”(physical association)	0.400
PIK3CD	NCK1	psi-mi:“MI:0915”(physical association)	0.400
PIK3CD	CD37	psi-mi:“MI:0915”(physical association)	0.400
PIK3CD	HRAS	psi-mi:“MI:0915”(physical association)	0.400
NS1		psi-mi:“MI:0914”(association)	0.350
NS1	SAC3D1	psi-mi:“MI:0914”(association)	0.350
NS1	ESYT2	psi-mi:“MI:0914”(association)	0.350
DDR1	PIK3CD	psi-mi:“MI:0914”(association)	0.350
SPP1	PIK3CD	psi-mi:“MI:0914”(association)	0.350

BioGRID (33): PIK3CD (Co-fractionation), PIK3CD (Affinity Capture-MS), PIK3CD (Affinity Capture-MS), PIK3CD (Negative Genetic), PIK3CD (Negative Genetic), PIK3CD (Negative Genetic), PIK3CD (Negative Genetic), PTPRZ1 (Negative Genetic), PIK3CD (Negative Genetic), PIK3CD (Negative Genetic), PIK3CD (Negative Genetic), PIK3CD (Affinity Capture-MS), PIK3CD (Affinity Capture-MS), PIK3CD (Two-hybrid), PIK3CD (Two-hybrid)

ESM2 similar proteins: A0A0G2K1Q8, B2RX12, E9PU17, E9PX95, F1MWM0, O00329, O15438, O35600, O75899, O88563, O88871, O94911, O95477, P41233, P55205, P58428, P78363, Q09427, Q09428, Q09429, Q2NKY8, Q5BJS0, Q5R607, Q5ZI74, Q6TL19, Q7L2E3, Q7TNJ2, Q80T41, Q84M24, Q8CF82, Q8IUA7, Q8K440, Q8K441, Q8K442, Q8K448, Q8K449, Q8LPK0, Q8N139, Q8NCL4, Q8R420

Diamond homologs: A0A0G2K344, O00329, O00443, O00750, O02697, O35904, O70167, O70173, O75747, P32871, P42336, P42337, P42338, P48736, P50520, P54673, P54674, P54675, P54676, Q0WPX9, Q22258, Q54UC0, Q5RAY1, Q61194, Q8BTI9, Q8WN22, Q9C680, Q9FMJ0, Q9JHG7, Q9VK45, Q9Z1L0, P0C5E7, P22543, P39104, P42339, P42347, P42348, P54677, Q94125, Q95Q95

SIGNOR signaling

28 interactions.

A	Effect	B	Mechanism
ERBB3	up-regulates	PIK3CD	binding
ERBB4	up-regulates	PIK3CD	binding
IC-87114	down-regulates	PIK3CD	“chemical inhibition”
HRAS	up-regulates	PIK3CD	binding
KRAS	up-regulates	PIK3CD	binding
dactolisib	down-regulates	PIK3CD	“chemical inhibition”
pictrelisib	down-regulates	PIK3CD	“chemical inhibition”
BKM120	down-regulates	PIK3CD	“chemical inhibition”
idelalisib	down-regulates	PIK3CD	“chemical inhibition”
CH5132799	down-regulates	PIK3CD	“chemical inhibition”
1-[4-[[2-(2-amino-5-pyrimidinyl)-7-methyl-4-(4-morpholinyl)-6-thieno[3,2-d]pyrimidinyl]methyl]-1-piperazinyl]-2-hydroxy-1-propanone	down-regulates	PIK3CD	“chemical inhibition”
GSK1059615	down-regulates	PIK3CD	“chemical inhibition”
GSK2126458	down-regulates	PIK3CD	“chemical inhibition”
PI-103	down-regulates	PIK3CD	“chemical inhibition”
PIK-294	down-regulates	PIK3CD	“chemical inhibition”
PIK-90	down-regulates	PIK3CD	“chemical inhibition”
PKI-402	down-regulates	PIK3CD	“chemical inhibition”
PP121	down-regulates	PIK3CD	“chemical inhibition”
3-[2,4-diamino-7-(3-hydroxyphenyl)-6-pteridinyl]phenol	down-regulates	PIK3CD	“chemical inhibition”
XL765	down-regulates	PIK3CD	“chemical inhibition”
ZSTK-474	down-regulates	PIK3CD	“chemical inhibition”
ITGB4	up-regulates	PIK3CD	binding
PIK3CD	down-regulates	PIK3CD	phosphorylation
TNF	up-regulates	PIK3CD
PIK3R1	“up-regulates activity”	PIK3CD	binding
PIK3CD	up-regulates	Survival
PI3K	“up-regulates activity”	PIK3CD	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	19
Likely pathogenic	14
Uncertain significance	370
Likely benign	446
Benign	53

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1064709	NM_005026.5(PIK3CD):c.2161C>T (p.Gln721Ter)	Pathogenic
1064710	NM_005026.5(PIK3CD):c.1654del (p.Val552fs)	Pathogenic
1064711	NM_005026.5(PIK3CD):c.2558_2559del (p.Asp853fs)	Pathogenic
132807	NM_005026.5(PIK3CD):c.1573G>A (p.Glu525Lys)	Pathogenic
1500652	NM_005026.5(PIK3CD):c.171_178del (p.Leu58fs)	Pathogenic
2077526	NM_005026.5(PIK3CD):c.767dup (p.Cys257fs)	Pathogenic
2699590	NM_005026.5(PIK3CD):c.2164G>T (p.Glu722Ter)	Pathogenic
2810787	NM_005026.5(PIK3CD):c.1687C>T (p.Gln563Ter)	Pathogenic
2845778	NM_005026.5(PIK3CD):c.494_512del (p.Tyr165fs)	Pathogenic
2849187	NM_005026.5(PIK3CD):c.104_105del (p.Pro35fs)	Pathogenic
2849820	NM_005026.5(PIK3CD):c.2704C>T (p.Arg902Ter)	Pathogenic
3722778	NM_005026.5(PIK3CD):c.236dup (p.Gln80fs)	Pathogenic
3723252	NM_005026.5(PIK3CD):c.1708del (p.Ser570fs)	Pathogenic
422410	NM_005026.5(PIK3CD):c.3074A>G (p.Glu1025Gly)	Pathogenic
4734780	NM_005026.5(PIK3CD):c.1314_1333del (p.Leu439fs)	Pathogenic
4735607	NM_005026.5(PIK3CD):c.223C>T (p.Gln75Ter)	Pathogenic
4762344	NM_005026.5(PIK3CD):c.157dup (p.Ala53fs)	Pathogenic
541084	NM_005026.5(PIK3CD):c.236_237del (p.Gln79fs)	Pathogenic
88675	NM_005026.5(PIK3CD):c.3061G>A (p.Glu1021Lys)	Pathogenic
132806	NM_005026.5(PIK3CD):c.1002C>A (p.Asn334Lys)	Likely pathogenic
132808	NM_005026.5(PIK3CD):c.1246T>C (p.Cys416Arg)	Likely pathogenic
1406866	NM_005026.5(PIK3CD):c.1570T>A (p.Tyr524Asn)	Likely pathogenic
1457684	NM_005026.5(PIK3CD):c.1571A>C (p.Tyr524Ser)	Likely pathogenic
2582528	NM_005026.5(PIK3CD):c.266_273del (p.Leu89fs)	Likely pathogenic
2733822	NM_005026.5(PIK3CD):c.371G>A (p.Gly124Asp)	Likely pathogenic
3237514	NM_005026.5(PIK3CD):c.317dup (p.Asp107fs)	Likely pathogenic
4684966	NM_005026.5(PIK3CD):c.241G>A (p.Glu81Lys)	Likely pathogenic
4684967	NM_005026.5(PIK3CD):c.1574A>C (p.Glu525Ala)	Likely pathogenic
4795433	NM_005026.5(PIK3CD):c.1571A>G (p.Tyr524Cys)	Likely pathogenic
578525	NM_005026.5(PIK3CD):c.1002C>G (p.Asn334Lys)	Likely pathogenic

SpliceAI

4381 predictions. Top by Δscore:

Variant	Effect	Δscore
1:9653345:C:G	donor_gain	1.0000
1:9691567:GAGAG:G	donor_gain	1.0000
1:9691570:AGGTA:A	donor_loss	1.0000
1:9691572:GT:G	donor_loss	1.0000
1:9691573:T:A	donor_loss	1.0000
1:9710416:A:AG	acceptor_gain	1.0000
1:9710417:T:G	acceptor_gain	1.0000
1:9710419:TTTA:T	acceptor_loss	1.0000
1:9710420:TTA:T	acceptor_loss	1.0000
1:9710421:TA:T	acceptor_loss	1.0000
1:9710422:A:AG	acceptor_gain	1.0000
1:9710422:A:C	acceptor_loss	1.0000
1:9710422:AG:A	acceptor_gain	1.0000
1:9710423:G:GG	acceptor_gain	1.0000
1:9710423:GG:G	acceptor_gain	1.0000
1:9710423:GGA:G	acceptor_gain	1.0000
1:9710423:GGAC:G	acceptor_gain	1.0000
1:9710423:GGACA:G	acceptor_gain	1.0000
1:9710593:GCAG:G	donor_gain	1.0000
1:9710594:CAGG:C	donor_loss	1.0000
1:9710595:AGG:A	donor_loss	1.0000
1:9710596:GGT:G	donor_loss	1.0000
1:9710597:GT:G	donor_loss	1.0000
1:9710598:T:G	donor_loss	1.0000
1:9715539:A:AG	acceptor_gain	1.0000
1:9715540:G:GG	acceptor_gain	1.0000
1:9715540:GCT:G	acceptor_gain	1.0000
1:9715765:CAAAG:C	donor_loss	1.0000
1:9715766:AAAG:A	donor_loss	1.0000
1:9715767:AAGGT:A	donor_loss	1.0000

AlphaMissense

6879 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:9722344:A:G	K779E	1.000
1:9722346:G:C	K779N	1.000
1:9722346:G:T	K779N	1.000
1:9722581:T:A	W801R	1.000
1:9722581:T:C	W801R	1.000
1:9723274:T:C	L859P	1.000
1:9723997:T:C	F875L	1.000
1:9723998:T:C	F875S	1.000
1:9723999:C:A	F875L	1.000
1:9723999:C:G	F875L	1.000
1:9724010:G:A	C879Y	1.000
1:9724011:T:G	C879W	1.000
1:9724013:C:A	A880D	1.000
1:9724016:G:A	G881D	1.000
1:9724023:T:G	C883W	1.000
1:9724051:G:C	D893H	1.000
1:9724052:A:C	D893A	1.000
1:9724052:A:G	D893G	1.000
1:9724052:A:T	D893V	1.000
1:9724068:C:A	N898K	1.000
1:9724068:C:G	N898K	1.000
1:9724070:T:A	I899N	1.000
1:9724070:T:G	I899S	1.000
1:9724087:G:T	G905W	1.000
1:9724088:G:A	G905E	1.000
1:9724088:G:T	G905V	1.000
1:9724282:C:G	H909D	1.000
1:9724289:A:C	D911A	1.000
1:9724289:A:T	D911V	1.000
1:9724290:T:A	D911E	1.000

dbSNP variants (sampled 300 via entrez): RS1000060436 (1:9662289 C>T), RS1000088267 (1:9647809 C>A,G), RS1000094886 (1:9644748 C>G), RS1000108829 (1:9695642 G>C), RS1000114064 (1:9625604 C>A), RS1000151753 (1:9710291 T>A,C), RS1000207360 (1:9707720 A>G), RS1000216606 (1:9701130 C>T), RS1000235207 (1:9628829 G>A,C), RS1000269113 (1:9710815 C>T), RS1000279171 (1:9660062 T>C), RS1000288293 (1:9700897 C>T), RS1000292516 (1:9697693 AT>A), RS1000305442 (1:9650471 A>G), RS1000315161 (1:9629074 A>G)

Disease associations

OMIM: gene MIM:602839 | disease phenotypes: MIM:615513, MIM:613328, MIM:619281

GenCC curated gene-disease

Disease	Classification	Inheritance
immunodeficiency 14	Definitive	Autosomal dominant
immunodeficiency 14b, autosomal recessive	Strong	Autosomal recessive
activated PI3K-delta syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (2)

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

Disease	Classification	Inheritance
immunodeficiency 14b, autosomal recessive	Definitive	AR
immunodeficiency 14	Definitive	AD

Mondo (4): immunodeficiency 14 (MONDO:0014222), activated PI3K-delta syndrome (MONDO:0018338), combined immunodeficiency with faciooculoskeletal anomalies (MONDO:0013226), immunodeficiency 14b, autosomal recessive (MONDO:0023655)

Orphanet (4): Activated PI3K-delta syndrome (Orphanet:397596), Activated PI3K-delta syndrome 1 (Orphanet:693661), Combined immunodeficiency with facio-oculo-skeletal anomalies (Orphanet:221139), Moyamoya angiopathy (Orphanet:477768)

HPO phenotypes

142 total (30 of 142 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000010	Recurrent urinary tract infections
HP:0000086	Ectopic kidney
HP:0000122	Unilateral renal agenesis
HP:0000218	High palate
HP:0000246	Sinusitis
HP:0000286	Epicanthus
HP:0000306	Abnormality of the chin
HP:0000316	Hypertelorism
HP:0000348	High forehead
HP:0000377	Abnormal pinna morphology
HP:0000389	Chronic otitis media
HP:0000411	Protruding ear
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000490	Deeply set eye
HP:0000509	Conjunctivitis
HP:0000609	Optic nerve hypoplasia
HP:0000620	Dacryocystitis
HP:0000648	Optic atrophy
HP:0000924	Abnormality of the skeletal system
HP:0000938	Osteopenia
HP:0000953	Hyperpigmentation of the skin
HP:0000988	Skin rash
HP:0000998	Hypertrichosis
HP:0001249	Intellectual disability
HP:0001251	Ataxia

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST002875_38	Diisocyanate-induced asthma	1.000000e-06
GCST004625_2	Monocyte count	2.000000e-09
GCST004635_1	Testicular germ cell tumor	6.000000e-13
GCST006304_1	Irritable bowel syndrome	3.000000e-06
GCST008888_1	Systemising	1.000000e-06
GCST90002381_511	Eosinophil count	3.000000e-27
GCST90002382_55	Eosinophil percentage of white cells	2.000000e-19
GCST90002388_282	Lymphocyte count	4.000000e-09
GCST90002393_114	Monocyte count	2.000000e-19

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0006995	response to diisocyanate
EFO:0005091	monocyte count
EFO:0010221	systemising measurement
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004587	lymphocyte count

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C585640	Activated PI3K-delta Syndrome (supp.)
C567641	Roifman-Chitayat Syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2111432 (PROTEIN COMPLEX), CHEMBL3130 (SINGLE PROTEIN), CHEMBL3559703 (PROTEIN COMPLEX GROUP), CHEMBL3885617 (PROTEIN FAMILY), CHEMBL6193791 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195501 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195549 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

66 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 338,553 (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
CHEMBL2216870	IDELALISIB	4	10,163
CHEMBL2396661	ALPELISIB	4	6,070
CHEMBL3039502	DUVELISIB	4	5,332
CHEMBL3218576	COPANLISIB	4	4,529
CHEMBL3948730	UMBRALISIB	4	2,833
CHEMBL113	CAFFEINE	4	200,591
CHEMBL1355736	THEOPHYLLINE	4	752
CHEMBL3545068	COPANLISIB HYDROCHLORIDE	4	1,306
CHEMBL3643413	LENIOLISIB	4	341
CHEMBL4650215	INAVOLISIB	4	876
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL2017974	BUPARLISIB	3	6,568
CHEMBL2387080	TASELISIB	3	3,473
CHEMBL4297615	PARSACLISIB	3	666
CHEMBL5095079	POVORCITINIB	3	224
CHEMBL592445	GEDATOLISIB	3	3,177
CHEMBL603469	LESTAURTINIB	3
CHEMBL1236962	OMIPALISIB	2	3,989
CHEMBL3188551	GSK-2636771	2
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL3984425	EGANELISIB	2
CHEMBL4438249	AMDIZALISIB	2
CHEMBL4800252	RISOVALISIB	2
CHEMBL521851	PICTILISIB	2
CHEMBL586702	ZSTK-474	2
CHEMBL1234354	PF-04691502	2
CHEMBL1684984	IZORLISIB	2
CHEMBL1922094	APITOLISIB	2

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 (78 total), top 25:

Ligand	Action	Affinity	Parameter
GSK2292767	Inhibition	10.1	pKi
taselisib	Inhibition	10.1	pKi
KU-0060648	Inhibition	10.0	pIC50
nemiralisib	Inhibition	9.9	pIC50
PF-06843195	Inhibition	9.55	pKi
amdizalisib	Inhibition	9.52	pIC50
compound 15a [PMID: 32069401]	Inhibition	9.3	pIC50
compound 20f [PMID: 28520415]	Inhibition	9.2	pIC50
AZD8154	Inhibition	9.15	pIC50
copanlisib	Inhibition	9.15	pIC50
compound (S)-29 [PMID: 37606563]	Inhibition	9.1	pIC50
compound 5d [PMID: 31335136]	Inhibition	8.96	pIC50
compound 82 [PMID: 21332118]	Inhibition	8.92	pKi
compound 52 [PMID: 28541707]	Inhibition	8.77	pIC50
CHF-6523	Inhibition	8.77	pIC50
bosmolisib	Inhibition	8.7	pIC50
linperlisib	Inhibition	8.62	pIC50
RV6153	Inhibition	8.6	pIC50
idelalisib	Inhibition	8.6	pIC50
duvelisib	Inhibition	8.6	pIC50
pictilisib	Inhibition	8.52	pIC50
PI-103	Inhibition	8.52	pIC50
puquitinib	Inhibition	8.48	pIC50
compound 2q [PMID: 30986068]	Inhibition	8.41	pIC50
panulisib	Inhibition	8.4	pIC50

Binding affinities (BindingDB)

3963 measured of 6099 human assays (6100 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(3R,10R,13E,16S)-10-[(4-methoxyphenyl)methyl]-3-(2-methylpropyl)-16-[(E,2R)-4-phenylbut-3-en-2-yl]-1,4-dioxa-8,11-diazacyclohexadec-13-ene-2,5,9,12-tetrone	KI	0.016 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(2S)-2-[[2-[2-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide	KI	0.023 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
Inavolisib	KI	0.034 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
(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
9-[1-methyl-5-[(3R)-4-methyl-3-propan-2-ylpiperazin-1-yl]pyrazol-4-yl]-2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine	IC50	0.048 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta 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
2-amino-4-[[(1S)-1-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]-6-methylpyrimidine-5-carbonitrile	IC50	0.1 nM	US-9765060: Phosphatidylinositol 3-kinase inhibitors
12-[2-(1-methylpiperidin-2-yl)pyrrolidin-1-yl]-4-[5-methyl-2-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]-9-oxa-3,6,13-triazatricyclo[8.4.0.02,6]tetradeca-1(14),2,4,10,12-pentaene	IC50	0.102 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
(2S)-2-[methyl-[2-(2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]amino]propanamide	KI	0.107 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-9-[2-[(3R)-1-propan-2-ylpiperidin-3-yl]azetidin-1-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine	IC50	0.16 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
9-(9-methyl-1,9-diazaspiro[4.5]decan-1-yl)-2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine	IC50	0.178 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
(2S)-2-[[2-[2-(2,2,2-trifluoroethyl)-1,2,4-triazol-3-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]oxy]propanamide	KI	0.186 nM	US-10112932: Benzoxazepin oxazolidinone compounds and methods of use
5-methyl-3-phenyl-2-[(1S)-1-[[5-(1H-pyrrolo[2,3-b]pyridin-5-yl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-4-one	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
2-[(1S)-1-[[5-[1-(3-hydroxypropyl)pyrazol-4-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-5-methyl-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-4-one	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
US9388189, 145	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
N-[5-[4-amino-6-[[(1S)-1-(5-methyl-4-oxo-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidin-5-yl]-2-methoxy-3-pyridinyl]-4-hydroxybenzenesulfonamide	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
US9388189, 163	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
[3-hydroxy-5-(methanesulfonamido)phenyl] 4-amino-6-[[(1S)-1-(5-methyl-4-oxo-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]pyrimidine-5-carboxylate	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
N-[6-[4-[[(1S)-1-(5-methyl-4-oxo-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-1H-indol-4-yl]methanesulfonamide	IC50	0.2 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
(S)-4-acetyl-1-(5-(4-amino-5- (trifluoromethyl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)-2-fluorophenyl)-3,3,6- trimethylpiperazin-2-one	IC50	0.2 nM	US-10214537
(S)-4-acetyl-1-(5-(4-amino-5- chloropyrrolo[2,1-f][1,2,4]triazin-7- yl)-2-fluorophenyl)-3,3,6- trimethylpiperazin-2-one	IC50	0.2 nM	US-10214537
(S)-4-acetyl-1-(5-(4-amino-5-(1-((S)- 1,1,1-trifluoropropan-2-yl)-1H- pyrazol-5-yl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)-2-fluorophenyl)-3,3,6- trimethylpiperazin-2-one	IC50	0.2 nM	US-10214537
(S)-4-acetyl-1-(5-(4-amino-5-(1- methyl-1H-pyrazol-4-yl)pyrrolo[2,1-f] [1,2,4]triazin-7-yl)-2-fluorophenyl)- 3,3,6-trimethylpiperazin-2-one	IC50	0.2 nM	US-10214537
2-(4-acetyl-3-ethyl-3-methyl-2- oxopiperazin-1-yl)-4-(4-amino-5- chloropyrrolo[2,1-f][1,2,4]triazin-7- yl)benzonitrile	IC50	0.2 nM	US-10214537
(R)-2-(4-acetyl-3-ethyl-3-methyl-2- oxopiperazin-1-yl)-4-(4-amino-5- chloropyrrolo[2,1-f][1,2,4]triazin-7- yl)benzonitrile	IC50	0.2 nM	US-10214537
(S)-2-(4-acetyl-3-ethyl-3-methyl-2- oxopiperazin-1-yl)-4-(4-amino-5- (trifluoromethyl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)benzonitrile	IC50	0.2 nM	US-10214537
4-[4-amino-5-(trifluoromethyl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-2-(2,2,5-trimethyl-3-oxomorpholin-4-yl)benzonitrile	IC50	0.2 nM	US-10214537
4-(4-amino-5-(1-(2,2,2-trifluoroethyl)- 1H-pyrazol-5-yl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)-2-((5S,6S)-2,2,5,6- tetramethyl-3-oxomorpholino) benzonitrile	IC50	0.2 nM	US-10214537
(R)-4-(4-amino-5-(trifluoromethyl) pyrrolo[2,1-f][1,2,4]triazin-7-yl)-2- (2,2,5-trimethyl-3-oxomorpholino) benzamide	IC50	0.2 nM	US-10214537
N-(2-(4-(5-(4-amino-5-chloropyrrolo [2,1-f][1,2,4]triazin-7-yl)-2- fluorophenyl)-2,2-dimethyl-3- oxopiperazin-1-yl)-2-oxoethyl) acetamide	IC50	0.2 nM	US-10214537
1-(3-(4-amino-5-chloropyrrolo[2,1-f] [1,2,4]triazin-7-yl)phenyl)-4-(3- hydroxy-3-methylbutanoyl)-3,3- dimethylpiperazin-2-one	IC50	0.2 nM	US-10214537
N-(2-(4-(5-(4-amino-5- (trifluoromethyl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)-2-cyanophenyl)-2,2- dimethyl-3-oxopiperazin-1-yl)-2- oxoethyl)methanesulfonamide	IC50	0.2 nM	US-10214537
(S)-1-(5-(4-amino-5-chloropyrrolo [2,1-f][1,2,4]triazin-7-yl)-2- fluorophenyl)-3,3,6-trimethyl-4-(2- (methylsulfonyl)acetyl)piperazin-2-one	IC50	0.2 nM	US-10214537
4-acetyl-1-(5-(4-amino-5- (trifluoromethyl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)-2-(methoxymethyl) phenyl)-3,3-dimethylpiperazin-2-one	IC50	0.2 nM	US-10214537
2-methyl-2-[3-[1-methyl-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-5-yl]piperidin-1-yl]propan-1-ol	IC50	0.262 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
N,N-dimethyl-1-[1-[2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepin-9-yl]pyrrolidin-2-yl]methanamine	IC50	0.288 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
2-methyl-2-[3-[5-[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]piperidin-1-yl]propan-1-ol	IC50	0.292 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
9-[1-methyl-5-(1-propan-2-ylpiperidin-3-yl)pyrazol-4-yl]-2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine	IC50	0.293 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use
5-methyl-3-phenyl-2-[(1S)-1-[[5-(2-phenylethynyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-4-one	IC50	0.3 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
5-methyl-2-[(1S)-1-[[5-(3-morpholin-4-ylsulfonylphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]ethyl]-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-4-one	IC50	0.3 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
US9388189, 155	IC50	0.3 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
[3-hydroxy-5-[4-[[(1S)-1-(5-methyl-4-oxo-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]urea	IC50	0.3 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
3-(methanesulfonamido)-N,N-dimethyl-5-[4-[[(1S)-1-(5-methyl-4-oxo-3-phenyl-1,2-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]benzamide	IC50	0.3 nM	US-9388189: Pyrrolotriazinone derivatives as PI3K inhibitors
(S)-2,4-diamino-6-(((5-chloro-4-oxo-3-phenyl-3,4-dihydroquinazoline-2-yl)(phenyl)methyl)amino)pyrimidine-5-carbonitrile	IC50	0.3 nM	US-9765060: Phosphatidylinositol 3-kinase inhibitors
(S)-4-acetyl-1-(5-(4-amino-5-(1- cyclopropyl-1H-pyrazol-4-yl)pyrrolo [2,1-f][1,2,4]triazin-7-yl)-2- fluorophenyl)-3,3,6- trimethylpiperazin-2-one	IC50	0.3 nM	US-10214537
2-(4-acetyl-3-ethyl-3-methyl-2- oxopiperazin-1-yl)-4-(4-amino-5- (trifluoromethyl)pyrrolo[2,1-f][1,2,4] triazin-7-yl)benzonitrile	IC50	0.3 nM	US-10214537
N-(3-(4-(5-(4-amino-5-chloropyrrolo [2,1-f][1,2,4]triazin-7-yl)-2- cyanophenyl)-2,2-dimethyl-3- oxopiperazin-1-yl)-3-oxopropyl) acetamide	IC50	0.3 nM	US-10214537
2-(5-methyl-2-propan-2-yl-1,2,4-triazol-3-yl)-9-[3-(1-propan-2-ylpiperidin-3-yl)pyrazolidin-4-yl]-5,6-dihydroimidazo[1,2-d][1,4]benzoxazepine	IC50	0.311 nM	US-9090628: Benzoxazepin compounds selective for PI3K P110 delta and methods of use

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	Ki	0.01	nM	CHEMBL4850297
11.00	Ki	0.01	nM	CHEMBL4869783
10.90	Ki	0.01259	nM	CHEMBL4167702
10.80	Ki	0.01585	nM	CHEMBL4858875
10.70	Ki	0.02	nM	OMIPALISIB
10.62	Ki	0.024	nM	OMIPALISIB
10.60	Ki	0.02512	nM	CHEMBL4873390
10.60	Ki	0.02512	nM	CHEMBL4165185
10.60	Ki	0.02512	nM	CHEMBL4175571
10.50	Ki	0.03162	nM	CHEMBL4175737
10.40	IC50	0.04	nM	CHEMBL4441003
10.40	Ki	0.03981	nM	CHEMBL4169192
10.37	IC50	0.043	nM	CHEMBL5947580
10.37	IC50	0.043	nM	CHEMBL5806327
10.32	IC50	0.048	nM	CHEMBL3704739
10.30	Ki	0.05012	nM	CHEMBL4173087
10.30	Ki	0.05012	nM	CHEMBL4174874
10.22	Ki	0.06	nM	CHEMBL4864407
10.22	IC50	0.06	nM	OMIPALISIB
10.20	Ki	0.0631	nM	CHEMBL4170075
10.15	Ki	0.07	nM	OMIPALISIB
10.10	Ki	0.07943	nM	CHEMBL4434674
10.10	Ki	0.07943	nM	CHEMBL4855234
10.10	Ki	0.08	nM	CHEMBL4860369
10.10	IC50	0.08	nM	CHEMBL4434674
10.10	Ki	0.079	nM	TASELISIB
10.07	IC50	0.086	nM	CHEMBL5927459
10.07	IC50	0.086	nM	CHEMBL5878158
10.05	IC50	0.09	nM	CHEMBL4868117
10.00	IC50	0.1	nM	CHEMBL3403664
10.00	IC50	0.1	nM	CHEMBL3805572
10.00	IC50	0.1	nM	CHEMBL3805430
10.00	IC50	0.1	nM	CHEMBL4541570
10.00	Ki	0.1	nM	CHEMBL5555605
10.00	IC50	0.1	nM	CHEMBL3805760
9.99	IC50	0.102	nM	CHEMBL3704656
9.97	IC50	0.107	nM	CHEMBL3704656
9.97	IC50	0.106	nM	CHEMBL3704656
9.92	Ki	0.12	nM	TASELISIB
9.91	Ki	0.122	nM	CHEMBL2331664
9.90	Ki	0.1259	nM	NEMIRALISIB
9.90	Ki	0.1259	nM	CHEMBL4867203
9.89	IC50	0.13	nM	CHEMBL3805760
9.89	Ki	0.13	nM	CHEMBL4878958
9.85	IC50	0.14	nM	CHEMBL6058341
9.85	IC50	0.14	nM	CHEMBL5851512
9.82	IC50	0.15	nM	CHEMBL3805664
9.80	IC50	0.16	nM	CHEMBL3704723
9.75	IC50	0.178	nM	CHEMBL3704706
9.74	IC50	0.18	nM	CHEMBL4166144

PubChem BioAssay actives

4446 with measured affinity, of 6100 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
N-[3-[4-[[(1S)-1-(5-methyl-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]-7H-pyrrolo[2,3-d]pyrimidin-5-yl]phenyl]methanesulfonamide	1553507: Inhibition of PI3Kdelta (unknown origin) preincubated for 30 mins followed by insulin stimulation for 5 mins by Western blot analysis	ic50	<0.0001	uM
N-[2-[2-fluoro-4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
N-[2-[4-[(4-tert-butylpiperazin-1-yl)methyl]phenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
N-[2-[4-[(4-tert-butylpiperazin-1-yl)methyl]-2-fluorophenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
2-methoxy-5-morpholin-4-yl-N-[2-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]-4-pyridinyl]pyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
N-[2-[4-[[(2R,6S)-2,6-dimethylmorpholin-4-yl]methyl]-2-fluorophenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
5-(3,6-dihydro-2H-pyran-4-yl)-2-methoxy-N-[5-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]-3-pyridinyl]pyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
5-(3,6-dihydro-2H-pyran-4-yl)-2-methoxy-N-[5-[4-[[(3R,5S)-3,4,5-trimethylpiperazin-1-yl]methyl]phenyl]-3-pyridinyl]pyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
5-(3,6-dihydro-2H-pyran-4-yl)-2-methoxy-N-[5-[6-[(4-propan-2-ylpiperazin-1-yl)methyl]-3-pyridinyl]-3-pyridinyl]pyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
5-(3,6-dihydro-2H-pyran-4-yl)-N-[5-[4-[[(2R,6S)-2,6-dimethylmorpholin-4-yl]methyl]phenyl]-3-pyridinyl]-2-methoxypyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	<0.0001	uM
2,4-difluoro-N-[2-methoxy-5-(4-pyridazin-4-ylquinolin-6-yl)-3-pyridinyl]benzenesulfonamide	1994269: Inhibition of P13Kdelta (unknown origin) assessed as inhibition constant	ki	<0.0001	uM
2-amino-4-[[(1S)-1-(5-chloro-4-oxo-3-phenylquinazolin-2-yl)ethyl]amino]-6-methylpyrimidine-5-carbonitrile	1299722: Inhibition human full length PI3Kdelta catalytic subunit/p85alpha assessed as formation of PIP3 after 30 mins by europium labeled GRP-based TR-FRET assay	ic50	0.0001	uM
3-phenyl-2-[1-(7H-purin-6-ylamino)ethyl]quinolizin-4-one	1553490: Inhibition of PI3Kdelta (unknown origin)	ic50	0.0001	uM
2-(4-ethylpiperazin-1-yl)-N-[4-(2-morpholin-4-yl-4-oxochromen-8-yl)dibenzothiophen-1-yl]acetamide	768757: Inhibition of PI-3K delta (unknown origin)	ic50	0.0001	uM
2-[(1S)-1-[(6-amino-5-ethynylpyrimidin-4-yl)amino]ethyl]-5-chloro-3-phenylquinazolin-4-one	1299722: Inhibition human full length PI3Kdelta catalytic subunit/p85alpha assessed as formation of PIP3 after 30 mins by europium labeled GRP-based TR-FRET assay	ic50	0.0001	uM
N-[2-[3-fluoro-4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	0.0001	uM
N-[2-[2-fluoro-4-[[4-(2-hydroxypropan-2-yl)piperidin-1-yl]methyl]phenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	0.0001	uM
N-[2-[2,3-difluoro-4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]-4-pyridinyl]-2-methoxy-5-morpholin-4-ylpyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	0.0001	uM
2-(4-acetyl-3,3-dimethyl-2-oxopiperazin-1-yl)-4-[4-amino-5-(trifluoromethyl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]benzonitrile	1448761: Inhibition of PI3Kdelta (unknown origin) after 60 mins using fluorescein-labeled kinase tracer by HTRF assay	ic50	0.0001	uM
2-methoxy-5-morpholin-4-yl-N-[5-[4-[(4-propan-2-ylpiperazin-1-yl)methyl]phenyl]-3-pyridinyl]pyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	0.0001	uM
2-[(S)-cyclopropyl-(7H-purin-6-ylamino)methyl]-5-methyl-3-phenylquinazolin-4-one	1777368: Inhibition of recombinant human full length His-tagged p110delta/p85alpha expressed in baculovirus expression system measured after 60 mins in presence of ATP by ATP-competitive binding assay	ic50	0.0001	uM
5-(3,6-dihydro-2H-pyran-4-yl)-2-methoxy-N-[5-[4-(piperazin-1-ylmethyl)phenyl]-3-pyridinyl]pyridine-3-sulfonamide	1768974: Inhibition of recombinant human N-terminal His6-tagged full length P110delta/full length untagged human p85alpha expressed in baculovirus infected Sf21 insect cells using PIP2 as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by HTRF assay	ki	0.0001	uM
5-[(1S)-1-[4-amino-3-(3-fluoro-5-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-2-tert-butyl-4-chloropyridazin-3-one	2065839: Inhibition of recombinant human PI3Kdelta using L-alpha-phosphatidylinositol sodium salt and L-alpha-phosphatidyl-L-serine as substrate incubated for 60 mins in presence of ATP by ADP-glo kinase assay	ki	0.0001	uM
1-[1-[(2S)-2-hydroxypropanoyl]piperidin-4-yl]-3-methyl-8-(6-methyl-3-pyridinyl)imidazo[4,5-c][1,5]naphthyridin-2-one	731922: Inhibition of human PI3Kdelta	ki	0.0001	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	1586658: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by HTRF method	ki	0.0001	uM
2-[6-(1H-indol-4-yl)-1H-indazol-4-yl]-5-[(4-propan-2-ylpiperazin-1-yl)methyl]-1,3-oxazole	1586658: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate preincubated for 15 mins followed by substrate addition measured after 60 mins by HTRF method	ki	0.0001	uM
4-amino-6-[[(1S)-1-(6-fluoro-4-methylsulfonyl-3-phenylquinolin-2-yl)ethyl]amino]pyrimidine-5-carbonitrile	1192865: Inhibition of PI3Kdelta (unknown origin) assessed as inhibition of AKT phosphorylation by cell-based HTRF assay	ic50	0.0001	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	750479: Inhibition of PI3Kdelta (unknown origin)	ki	0.0001	uM
25-methoxy-31-methyl-22,22-dioxo-3,22lambda6,30-trithia-6,8,15,23,26-pentazahexacyclo[22.3.1.12,5.110,13.117,21.04,9]hentriaconta-1(28),2(31),4,6,8,10,12,17(29),18,20,24,26-dodecaen-16-one	1785807: Inhibition of human PI3K p110delta/p85alpha by HTRF assay	ki	0.0001	uM
18-fluoro-25-methoxy-31-methyl-22,22-dioxo-3,22lambda6,30-trithia-6,8,15,23,26-pentazahexacyclo[22.3.1.12,5.110,13.117,21.04,9]hentriaconta-1(28),2(31),4,6,8,10,12,17,19,21(29),24,26-dodecaen-16-one	1785807: Inhibition of human PI3K p110delta/p85alpha by HTRF assay	ki	0.0001	uM
5-methoxy-8,8-dioxo-8lambda6-thia-4,7,15,19,24,29-hexazahexacyclo[20.5.2.12,6.19,13.117,21.025,29]dotriaconta-1(28),2(32),3,5,9,11,13(31),17(30),18,20,22,24,26-tridecaen-14-one	1761293: Inhibition of human p110delta/p85alpha using PIP2 as substrate in presence of ATP measured by HTRF assay	ki	0.0001	uM
2,4-diamino-6-[[(1S)-1-[5-chloro-4-oxo-3-(1H-pyrazol-5-yl)quinazolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	1438035: Inhibition of human full length PI3K p110delta/p85 alpha using PIP2/ATP as substrate after 30 mins by TR-FRET assay	ic50	0.0002	uM
2-[(1S)-1-[[6-amino-5-(2H-tetrazol-5-yl)pyrimidin-4-yl]amino]ethyl]-3-phenylpyrrolo[2,1-f][1,2,4]triazin-4-one	1553507: Inhibition of PI3Kdelta (unknown origin) preincubated for 30 mins followed by insulin stimulation for 5 mins by Western blot analysis	ic50	0.0002	uM
N-[5-[2-amino-4-methyl-8-[(3R)-oxolan-3-yl]oxyquinazolin-6-yl]-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1355493: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate by ADP-Glo assay	ic50	0.0002	uM
N-[5-[2-amino-4-methyl-8-(oxan-4-yloxy)quinazolin-6-yl]-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1355493: Inhibition of PI3Kdelta (unknown origin) using PIP2 as substrate by ADP-Glo assay	ic50	0.0002	uM
2-amino-N-[7-methoxy-8-(3-morpholin-4-ylpropoxy)-2,3-dihydro-1H-imidazo[1,2-c]quinazolin-5-ylidene]pyrimidine-5-carboxamide	1560711: Inhibition of human full-length His-tagged p110delta/p85alpha expressed in baculovirus expression system using PIP2 as substrate measured after 1 hr by ADP-glo assay	ic50	0.0002	uM
4-[4-amino-5-(trifluoromethyl)pyrrolo[2,1-f][1,2,4]triazin-7-yl]-2-[(5S,6R)-2,2,5,6-tetramethyl-3-oxomorpholin-4-yl]benzonitrile	1469862: Inhibition of PI3Kdelta (unknown origin) after 60 mins using fluorescein-labeled kinase tracer by HTRF assay	ic50	0.0002	uM
4-[2-[2-[(1S)-1-[(2,6-diamino-5-cyanopyrimidin-4-yl)amino]propyl]-4-oxo-3-phenylquinazolin-5-yl]ethyl]-N-hydroxybenzamide	1605952: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay	ic50	0.0002	uM
6-[2-[(1S)-1-[(2-amino-5-cyano-6-methylpyrimidin-4-yl)amino]propyl]-4-oxo-3-phenylquinazolin-5-yl]-N-hydroxyhexanamide	1605952: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay	ic50	0.0002	uM
N-hydroxy-6-[4-oxo-3-phenyl-2-[(1S)-1-(7H-purin-6-ylamino)propyl]quinazolin-5-yl]hexanamide	1605952: Inhibition of human PI3Kdelta assessed as reduction in PIP3 product complex formation by measuring displacement of biotin-labelled PIP3 from complex using PIP2 as substrate measured after 30 mins in presence of ATP by HTRF assay	ic50	0.0002	uM
2-methoxy-N-[2-methoxy-5-[7-[[(2R)-4-(oxetan-3-yl)morpholin-2-yl]methoxy]-1,3-dihydro-2-benzofuran-5-yl]-3-pyridinyl]ethanesulfonamide	1528687: Binding affinity to PI3Kdelta in human HL60 cell extract measured after 2 hrs by kinobeads based pull down assay	kd	0.0002	uM
4-amino-6-[[(1S)-1-(3-chloro-6-phenylimidazo[1,2-a]pyridin-7-yl)ethyl]amino]pyrimidine-5-carbonitrile	1553490: Inhibition of PI3Kdelta (unknown origin)	ic50	0.0002	uM
N-[2-chloro-5-(4-imidazol-1-ylcinnolin-6-yl)-3-pyridinyl]benzenesulfonamide	1765908: Inhibition of PI3Kdelta (unknown origin)	ic50	0.0002	uM
5-[(1S)-1-[4-amino-3-(3-fluoro-5-hydroxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]ethyl]-2-tert-butyl-4-methoxypyridazin-3-one	2065839: Inhibition of recombinant human PI3Kdelta using L-alpha-phosphatidylinositol sodium salt and L-alpha-phosphatidyl-L-serine as substrate incubated for 60 mins in presence of ATP by ADP-glo kinase assay	ki	0.0002	uM
4-[3-[[2-(2-ethylbenzimidazol-1-yl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl]azetidin-1-yl]thiane 1,1-dioxide	764682: Inhibition of PI3Kdelta (unknown origin) assessed as formation of PIP3 by competitive fluorescence polarization assay	ki	0.0002	uM
4-amino-6-[[(1S)-1-[6-fluoro-3-phenyl-4-(piperazine-1-carbonyl)quinolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	1628650: Inhibition of polyHis tagged full length recombinant PI3Kdelta (unknown origin) expressed in Sf9 cells co-expressing p85 incubated for 20 mins by alpha screen assay	ic50	0.0002	uM
4-amino-6-[[(1S)-1-[6-fluoro-4-(2-methylsulfonylethylamino)-3-phenylquinolin-2-yl]ethyl]amino]pyrimidine-5-carbonitrile	1192861: Inhibition of PI3Kdelta (unknown origin) by biochemical Alphascreen assay	ic50	0.0002	uM
Duvelisib	1994225: Inhibition of P13Kdelta (unknown origin)	ic50	0.0002	uM
4-amino-6-[[(1S)-1-(6-fluoro-1-phenylbenzimidazol-2-yl)ethyl]amino]pyrimidine-5-carbonitrile	719910: Inhibition of PI3Kdelta	ki	0.0002	uM
1-[(3S)-3-[4-(2-aminopyrimidin-5-yl)-2-morpholin-4-yl-5,6-dihydropyrrolo[2,3-d]pyrimidin-7-yl]-3-methylpyrrolidin-1-yl]-2-methylpropan-1-one	1707453: Inhibition of recombinant human PI3K p110delta/p85alpha using phosphatidylinositol 4,5-bisphosphate as substrate preincubated for 15 mins followed by addition of ATP and measured after 30 mins by fluorescence polarisation assay	ki	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases expression, increases methylation	5
sodium arsenite	affects methylation, increases abundance, increases expression	3
Cannabidiol	affects cotreatment, decreases expression	3
Valproic Acid	increases expression, increases methylation, affects expression	3
moringin	affects cotreatment, decreases expression	2
trichostatin A	affects expression, increases expression	2
Arsenic	increases expression, increases abundance	2
Tretinoin	increases expression	2
GSK-J4	increases expression	1
dicrotophos	increases expression	1
tylophorine	increases expression	1
triphenyl phosphate	affects expression	1
bis(tri-n-butyltin)oxide	decreases expression	1
bisphenol A	decreases methylation	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
terbufos	increases methylation	1
sulforaphane	decreases expression	1
cobaltous chloride	decreases expression	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
celastrol	decreases expression	1
tamibarotene	increases expression	1
yessotoxin	increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
gedunin	decreases expression	1
entinostat	increases expression	1

ChEMBL screening assays

1111 unique, capped per target: 1094 binding, 8 admet, 8 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1261702	Binding	Inhibition of P110delta/p85-alpha	Discovery of 1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one as a highly potent, selective mammalian target of rapamycin (mTOR) inhibitor for the treatment of cancer. — J Med Chem
CHEMBL4403972	ADMET	Inhibition of AlexaFluor-labeled tracer 236 binding to full-length human His-tagged p110delta/p85alpha expressed in baculovirus expression system measured after 60 mins by LanthaScreen assay	The Discovery of 7-Methyl-2-[(7-methyl[1,2,4]triazolo[1,5-a]pyridin-6-yl)amino]-9-(tetrahydro-2H-pyran-4-yl)-7,9-dihydro-8H-purin-8-one (AZD7648), a Potent and Selective DNA-Dependent Protein Kinase (DNA-PK) Inhibitor. — J Med Chem
CHEMBL5123070	Toxicity	Inhibition of human PI3Kdelta by ADP-Glo assay	Discovery of novel 7,8-dihydropteridine-6(5H)-one-based DNA-PK inhibitors as potential anticancer agents via scaffold hopping strategy. — Eur J Med Chem

Cellosaurus cell lines

16 cell lines: 14 cancer cell line, 2 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_0093	RS4;11	Cancer cell line	Female
CVCL_B7YR	Abcam Raji PIK3CD KO	Cancer cell line	Male
CVCL_B9ZG	Abcam THP-1 PIK3CD KO	Cancer cell line	Male
CVCL_C0C4	CHCMUi001-A	Induced pluripotent stem cell	Female
CVCL_C7B5	Abcam PC-3 PIK3CD KO	Cancer cell line	Male
CVCL_D4ZR	SDQLCHi068-A	Induced pluripotent stem cell	Male
CVCL_D7XA	Ubigene A-549 PIK3CD KO	Cancer cell line	Male
CVCL_D8SR	Ubigene HCT 116 PIK3CD KO	Cancer cell line	Male
CVCL_E0KL	Ubigene HeLa PIK3CD KO	Cancer cell line	Female
CVCL_E8JJ	RS4;11 mouse MCL1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05438407	PHASE3	ACTIVE_NOT_RECRUITING	Pediatric Patients Aged 4 to 11 Years With APDS
NCT05693129	PHASE3	ACTIVE_NOT_RECRUITING	Pediatric Patients Aged 1 to 6 Years With APDS
NCT02593539	PHASE2	COMPLETED	Safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) Study of Repeat Doses of Inhaled Nemiralisib in Patients With APDS/PASLI
NCT03383380	PHASE1/PHASE2	COMPLETED	Rapamycin Treatment for Activated Phosphoinositide 3-Kinase δ Syndrome
NCT06694363	Not specified	RECRUITING	New Biomarker-based Strategy to Screen and Monitor for Activated Phosphoinositide 3-kinase δ Syndrome