activated PI3K-delta syndrome
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Also known as APDSsenescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation
Summary
activated PI3K-delta syndrome (MONDO:0018338) is a disease with 3 cohort genes and 5 clinical trials. The dominant Reactome pathway is Synthesis of PIPs at the plasma membrane (3 cohort genes). Top therapeutic interventions include leniolisib, sirolimus, and nemiralisib.
At a glance
- Prevalence: Unknown (Worldwide) [Orphanet-validated]
- Cohort genes: 3
- ClinVar variants: 43
- Phenotypes (HPO): 24
- Clinical trials: 5
Clinical features
Epidemiology
Prevalence records
1 prevalence record(s), Orphanet:
| Type | Class | Value | Geography | Validation |
|---|---|---|---|---|
| Cases/families | 250 | Worldwide | Validated |
Signs & symptoms
Clinical features (HPO)
24 HPO clinical features (Orphanet curated; top 24 by frequency):
| HPO ID | Term | Frequency |
|---|---|---|
| HP:0002090 | Pneumonia | Very frequent (80-99%) |
| HP:0200117 | Recurrent upper and lower respiratory tract infections | Very frequent (80-99%) |
| HP:0000403 | Recurrent otitis media | Frequent (30-79%) |
| HP:0001744 | Splenomegaly | Frequent (30-79%) |
| HP:0002110 | Bronchiectasis | Frequent (30-79%) |
| HP:0002240 | Hepatomegaly | Frequent (30-79%) |
| HP:0002716 | Lymphadenopathy | Frequent (30-79%) |
| HP:0002960 | Autoimmunity | Frequent (30-79%) |
| HP:0003496 | Increased circulating IgM level | Frequent (30-79%) |
| HP:0004313 | Decreased circulating antibody level | Frequent (30-79%) |
| HP:0010976 | Decreased total B cell count | Frequent (30-79%) |
| HP:0011109 | Chronic sinusitis | Frequent (30-79%) |
| HP:0011956 | Intestinal lymphoid nodular hyperplasia | Frequent (30-79%) |
| HP:0000252 | Microcephaly | Occasional (5-29%) |
| HP:0000365 | Hearing impairment | Occasional (5-29%) |
| HP:0001369 | Arthritis | Occasional (5-29%) |
| HP:0001508 | Failure to thrive | Occasional (5-29%) |
| HP:0002242 | Abnormal intestine morphology | Occasional (5-29%) |
| HP:0002665 | Lymphoma | Occasional (5-29%) |
| HP:0011110 | Recurrent tonsillitis | Occasional (5-29%) |
| HP:0012758 | Neurodevelopmental delay | Occasional (5-29%) |
| HP:0031692 | Severe cytomegalovirus infection | Occasional (5-29%) |
| HP:0031693 | Severe Epstein Barr virus infection | Occasional (5-29%) |
| HP:0032170 | Severe varicella zoster infection | Occasional (5-29%) |
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | activated PI3K-delta syndrome |
| Mondo ID | MONDO:0018338 |
| MeSH | C585640 |
| Orphanet | 397596 |
| SNOMED CT | 711480000 |
| GARD | 0011983 |
| Is cancer (heuristic) | no |
Also known as: APDS · senescent T-cells-lymphadenopathy-immunodeficiency syndrome due to p110delta-activating mutation
Data availability: 43 ClinVar variants · 3 GenCC gene-disease records.
Disease family
An umbrella term covering 2 Mondo subtypes.
Classification path: disease › human disease › disease by body system or component › immune system disorder › inborn error of immunity › B cell deficiency › agammaglobulinemia › activated PI3K-delta syndrome
Related subtypes (9): congenital agammaglobulinemia, immunodeficiency 61, Good syndrome, isolated agammaglobulinemia, syndromic agammaglobulinemia, agammaglobulinemia 9, autosomal recessive, agammaglobulinemia 10, autosomal dominant, agammaglobulinemia, autosomal recessive, due to BOB1 deficiency, agammaglobulinemia 8b, autosomal recessive
Subtypes (2): immunodeficiency 14, immunodeficiency 36 with lymphoproliferation
Genetics & variants
GWAS landscape
No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.
Variant details and genetic-evidence tiers
ClinVar germline variants
43 retrieved; paginated sample, class counts are floors:
36 uncertain significance, 6 likely benign, 1 conflicting classifications of pathogenicity
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 1047215 | NM_181523.3(PIK3R1):c.343C>G (p.Leu115Val) | PIK3R1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1495102 | NM_005026.5(PIK3CD):c.1057A>G (p.Met353Val) | LOC126805612 | Uncertain significance | criteria provided, single submitter |
| 4075729 | NM_005026.5(PIK3CD):c.1318T>C (p.Tyr440His) | LOC126805612 | Uncertain significance | criteria provided, single submitter |
| 1035901 | NM_005026.5(PIK3CD):c.2503G>A (p.Ala835Thr) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 1038802 | NM_005026.5(PIK3CD):c.1478A>C (p.Glu493Ala) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 1041355 | NM_005026.5(PIK3CD):c.866A>G (p.Gln289Arg) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 1056408 | NM_005026.5(PIK3CD):c.923C>T (p.Ala308Val) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 1061373 | NM_005026.5(PIK3CD):c.1402G>A (p.Ala468Thr) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1162831 | NM_005026.5(PIK3CD):c.2461C>T (p.Arg821Cys) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1328117 | NM_005026.5(PIK3CD):c.1579G>A (p.Glu527Lys) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 1399114 | NM_005026.5(PIK3CD):c.1121G>A (p.Arg374Gln) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2110452 | NM_005026.5(PIK3CD):c.113G>T (p.Arg38Leu) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 2572869 | NM_005026.5(PIK3CD):c.3057T>A (p.Phe1019Leu) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2805124 | NM_005026.5(PIK3CD):c.2863C>T (p.Arg955Trp) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 2866391 | NM_005026.5(PIK3CD):c.1738C>G (p.Leu580Val) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 2890917 | NM_005026.5(PIK3CD):c.2945G>A (p.Arg982Gln) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 3418574 | NM_005026.5(PIK3CD):c.2117C>A (p.Thr706Asn) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 3615597 | NM_005026.5(PIK3CD):c.896C>T (p.Pro299Leu) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 659165 | NM_005026.5(PIK3CD):c.692C>T (p.Pro231Leu) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 663967 | NM_005026.5(PIK3CD):c.2320G>A (p.Val774Met) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 845740 | NM_005026.5(PIK3CD):c.2869C>T (p.Arg957Trp) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 850940 | NM_005026.5(PIK3CD):c.971G>A (p.Arg324His) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 943206 | NM_005026.5(PIK3CD):c.5C>T (p.Pro2Leu) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 951744 | NM_005026.5(PIK3CD):c.401C>T (p.Pro134Leu) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 960245 | NM_005026.5(PIK3CD):c.2206G>A (p.Asp736Asn) | PIK3CD | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 963563 | NM_005026.5(PIK3CD):c.221A>G (p.Asn74Ser) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 965978 | NM_005026.5(PIK3CD):c.155G>A (p.Arg52His) | PIK3CD | Uncertain significance | criteria provided, single submitter |
| 1337679 | NM_181523.3(PIK3R1):c.406G>A (p.Val136Met) | PIK3R1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 1491282 | NM_181523.3(PIK3R1):c.604G>A (p.Val202Ile) | PIK3R1 | Uncertain significance | criteria provided, multiple submitters, no conflicts |
| 2921958 | NM_181523.3(PIK3R1):c.949G>A (p.Val317Ile) | PIK3R1 | Uncertain significance | criteria provided, single submitter |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 37 · Orphanet: 20 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0
GenCC gene–disease validity (cohort genes)
the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.
| Gene | Classification | Inheritance | Disease | Records |
|---|---|---|---|---|
| PIK3CD | Supportive | Autosomal dominant | activated PI3K-delta syndrome | 7 |
| PIK3R1 | Supportive | Autosomal dominant | activated PI3K-delta syndrome | 13 |
| PTEN | Supportive | Autosomal dominant | activated PI3K-delta syndrome | 17 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| PIK3CD | Orphanet:221139 | Combined immunodeficiency with facio-oculo-skeletal anomalies |
| PIK3CD | Orphanet:33110 | Autosomal non-syndromic agammaglobulinemia |
| PIK3CD | Orphanet:693661 | Activated PI3K-delta syndrome 1 |
| PIK3R1 | Orphanet:3163 | SHORT syndrome |
| PIK3R1 | Orphanet:33110 | Autosomal non-syndromic agammaglobulinemia |
| PIK3R1 | Orphanet:693681 | Activated PI3K-delta syndrome 2 |
| PTEN | Orphanet:109 | Bannayan-Riley-Ruvalcaba syndrome |
| PTEN | Orphanet:137608 | Segmental outgrowth-lipomatosis-arteriovenous malformation-epidermal nevus syndrome |
| PTEN | Orphanet:145 | Hereditary breast and/or ovarian cancer syndrome |
| PTEN | Orphanet:201 | Cowden syndrome |
| PTEN | Orphanet:210548 | Macrocephaly-intellectual disability-autism syndrome |
| PTEN | Orphanet:2969 | Proteus-like syndrome |
| PTEN | Orphanet:494547 | Squamous cell carcinoma of the hypopharynx |
| PTEN | Orphanet:494550 | Squamous cell carcinoma of the larynx |
| PTEN | Orphanet:500464 | Squamous cell carcinoma of the nasal cavity and paranasal sinuses |
| PTEN | Orphanet:500478 | Squamous cell carcinoma of the oropharynx |
| PTEN | Orphanet:502363 | Squamous cell carcinoma of the oral cavity |
| PTEN | Orphanet:502366 | Squamous cell carcinoma of the lip |
| PTEN | Orphanet:65285 | Lhermitte-Duclos disease |
| PTEN | Orphanet:79076 | Juvenile polyposis of infancy |
Cohort genes → proteins
3 cohort genes, 3 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 3 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| PIK3CD | HGNC:8977 | ENSG00000171608 | O00329 | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform | gencc,clinvar |
| PIK3R1 | HGNC:8979 | ENSG00000145675 | P27986 | Phosphatidylinositol 3-kinase regulatory subunit alpha | gencc,clinvar |
| PTEN | HGNC:9588 | ENSG00000171862 | P60484 | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | gencc |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| PIK3CD | Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform | Phosphoinositide-3-kinase (PI3K) phosphorylates phosphatidylinositol (PI) and its phosphorylated derivatives at position 3 of the inositol ring to produce 3-phosphoinositides. |
| PIK3R1 | Phosphatidylinositol 3-kinase regulatory subunit alpha | Binds to activated (phosphorylated) protein-Tyr kinases, through its SH2 domain, and acts as an adapter, mediating the association of the p110 catalytic unit to the plasma membrane. |
| PTEN | Phosphatidylinositol 3,4,5-trisphosphate 3-phosphatase and dual-specificity protein phosphatase PTEN | Dual-specificity protein phosphatase, dephosphorylating tyrosine-, serine- and threonine-phosphorylated proteins. |
Protein-family classification
Druggable: 3 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0
Family distribution
Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.
| Family | Genes | Fold | FDR |
|---|---|---|---|
| Kinase | 2 | 18.5× | 0.008 |
| Phosphatase | 1 | 28.0× | 0.035 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| PIK3CD | Kinase | yes | 2.7.1.137 | PI3K_Ras-bd_dom, PI3/4_kinase_cat_dom, PI3K_accessory_dom |
| PIK3R1 | Kinase | yes | 2.7.1.153 | RhoGAP_dom, SH2, SH3_domain |
| PTEN | Phosphatase | yes | 3.1.3.16 | Tyr_Pase_dom, Tyr_Pase_cat, Tensin_C2-dom |
Expression context
Cohort genes with no expression data: 0.
3 cohort genes are a single-cell marker in ≥1 SCXA experiment.
Breadth distribution (Bgee present_calls)
| Bucket | Genes |
|---|---|
| narrow (1-5 tissues) | 0 |
| moderate (6-20) | 0 |
| broad (>20) | 3 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| calcaneal tendon | 2 |
| blood | 1 |
| granulocyte | 1 |
| lymph node | 1 |
| caput epididymis | 1 |
| corpus epididymis | 1 |
| endothelial cell | 1 |
| sperm | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| PIK3CD | 253 | ubiquitous | marker | granulocyte, blood, lymph node |
| PIK3R1 | 294 | ubiquitous | marker | calcaneal tendon, caput epididymis, corpus epididymis |
| PTEN | 256 | ubiquitous | marker | sperm, endothelial cell, calcaneal tendon |
Protein interactions among cohort
Intra-cohort edges: 2.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| PTEN | 11,626 |
| PIK3R1 | 5,168 |
| PIK3CD | 2,059 |
Intra-cohort edges
| A | B | Sources |
|---|---|---|
| PIK3CD | PIK3R1 | biogrid_interaction, intact, string_interaction |
| PIK3R1 | PTEN | string_interaction |
Structural data
PDB: 3 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| PIK3R1 | P27986 | 105 |
| PIK3CD | O00329 | 18 |
| PTEN | P60484 | 12 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 90. Enrichment computed across 3 evidence-associated genes (3 with Reactome annotation).
Pathways by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Synthesis of PIPs at the plasma membrane | 3 | 211.5× | 9e-06 | PIK3CD, PIK3R1, PTEN |
| Co-stimulation by ICOS | 2 | 692.1× | 9e-05 | PIK3CD, PIK3R1 |
| Erythropoietin activates Phosphoinositide-3-kinase (PI3K) | 2 | 634.4× | 9e-05 | PIK3CD, PIK3R1 |
| Regulation of signaling by CBL | 2 | 331.0× | 3e-04 | PIK3CD, PIK3R1 |
| Interleukin receptor SHC signaling | 2 | 271.9× | 3e-04 | PIK3CD, PIK3R1 |
| CD28 dependent PI3K/Akt signaling | 2 | 262.5× | 3e-04 | PIK3CD, PIK3R1 |
| Antigen activates B Cell Receptor (BCR) leading to generation of second messengers | 2 | 237.9× | 3e-04 | PIK3CD, PIK3R1 |
| Signaling by CSF1 (M-CSF) in myeloid cells | 2 | 230.7× | 3e-04 | PIK3CD, PIK3R1 |
| Interleukin-3, Interleukin-5 and GM-CSF signaling | 2 | 211.5× | 3e-04 | PIK3CD, PIK3R1 |
| RET signaling | 2 | 173.0× | 4e-04 | PIK3CD, PIK3R1 |
| Downstream TCR signaling | 2 | 85.5× | 0.001 | PIK3R1, PTEN |
| Constitutive Signaling by Aberrant PI3K in Cancer | 2 | 84.6× | 0.001 | PIK3CD, PIK3R1 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 2 | 64.5× | 0.002 | PIK3CD, PIK3R1 |
| PTEN Loss of Function in Cancer | 1 | 1903.3× | 0.003 | PTEN |
| PIP3 activates AKT signaling | 2 | 44.5× | 0.004 | PIK3CD, PIK3R1 |
| MET activates PI3K/AKT signaling | 1 | 634.4× | 0.008 | PIK3R1 |
| Activated NTRK3 signals through PI3K | 1 | 634.4× | 0.008 | PIK3R1 |
| Activated NTRK2 signals through PI3K | 1 | 543.8× | 0.009 | PIK3R1 |
| Signaling by LTK in cancer | 1 | 543.8× | 0.009 | PIK3R1 |
| PI3K/AKT activation | 1 | 423.0× | 0.011 | PIK3R1 |
| Regulation of PTEN mRNA translation | 1 | 380.7× | 0.011 | PTEN |
| IRS-mediated signalling | 1 | 346.1× | 0.011 | PIK3R1 |
| PI3K events in ERBB4 signaling | 1 | 346.1× | 0.011 | PIK3R1 |
| Regulation of PTEN localization | 1 | 346.1× | 0.011 | PTEN |
| GP1b-IX-V activation signalling | 1 | 317.2× | 0.011 | PIK3R1 |
| Signaling by FGFR4 in disease | 1 | 317.2× | 0.011 | PIK3R1 |
| Signaling by PDGFRA transmembrane, juxtamembrane and kinase domain mutants | 1 | 292.8× | 0.011 | PIK3R1 |
| Signaling by PDGFRA extracellular domain mutants | 1 | 292.8× | 0.011 | PIK3R1 |
| Signaling by LTK | 1 | 292.8× | 0.011 | PIK3R1 |
| Signaling by FLT3 ITD and TKD mutants | 1 | 253.8× | 0.011 | PIK3R1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 3 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| phosphatidylinositol 3-kinase/protein kinase B signal transduction | 3 | 210.7× | 1e-05 | PIK3CD, PIK3R1, PTEN |
| T cell differentiation | 2 | 255.3× | 0.001 | PIK3CD, PIK3R1 |
| B cell differentiation | 2 | 145.9× | 0.003 | PIK3CD, PIK3R1 |
| natural killer cell chemotaxis | 1 | 2808.7× | 0.007 | PIK3CD |
| negative regulation of synaptic vesicle clustering | 1 | 2808.7× | 0.007 | PTEN |
| regulation of toll-like receptor 4 signaling pathway | 1 | 1872.4× | 0.007 | PIK3R1 |
| negative regulation of keratinocyte migration | 1 | 1872.4× | 0.007 | PTEN |
| positive regulation of endoplasmic reticulum unfolded protein response | 1 | 1872.4× | 0.007 | PIK3R1 |
| mast cell chemotaxis | 1 | 1404.3× | 0.007 | PIK3CD |
| respiratory burst involved in defense response | 1 | 1404.3× | 0.007 | PIK3CD |
| rhythmic synaptic transmission | 1 | 1404.3× | 0.007 | PTEN |
| mast cell differentiation | 1 | 1404.3× | 0.007 | PIK3CD |
| myeloid leukocyte migration | 1 | 1404.3× | 0.007 | PIK3R1 |
| positive regulation of neutrophil apoptotic process | 1 | 1123.5× | 0.007 | PIK3CD |
| central nervous system myelin maintenance | 1 | 936.2× | 0.007 | PTEN |
| interleukin-18-mediated signaling pathway | 1 | 936.2× | 0.007 | PIK3R1 |
| B cell chemotaxis | 1 | 936.2× | 0.007 | PIK3CD |
| neutrophil extravasation | 1 | 936.2× | 0.007 | PIK3CD |
| positive regulation of epithelial tube formation | 1 | 936.2× | 0.007 | PIK3CD |
| protein stabilization | 2 | 44.6× | 0.007 | PIK3R1, PTEN |
| cell migration | 2 | 41.0× | 0.007 | PIK3CD, PTEN |
| negative regulation of cell cycle G1/S phase transition | 1 | 802.5× | 0.007 | PTEN |
| negative regulation of wound healing, spreading of epidermal cells | 1 | 802.5× | 0.007 | PTEN |
| immune response | 2 | 31.4× | 0.007 | PIK3CD, PIK3R1 |
| spindle assembly involved in female meiosis | 1 | 624.1× | 0.007 | PTEN |
| central nervous system neuron axonogenesis | 1 | 624.1× | 0.007 | PTEN |
| postsynaptic density assembly | 1 | 624.1× | 0.007 | PTEN |
| positive regulation of focal adhesion disassembly | 1 | 624.1× | 0.007 | PIK3R1 |
| neuron-neuron synaptic transmission | 1 | 561.7× | 0.007 | PTEN |
| negative regulation of peptidyl-serine phosphorylation | 1 | 561.7× | 0.007 | PTEN |
Therapeutics
Drug target analysis
Approved (phase 4): 2 · Phase ≥3: 2 · Phased (≥1): 2 · Undrugged: 1
Druggability breadth: 3 of 3 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Genes with an approved drug
The molecule shown is one approved compound that hits the gene — not necessarily a drug of choice or one indicated for this disease.
| Symbol | Example approved molecule |
|---|---|
| PIK3CD | IDELALISIB |
| PIK3R1 | IDELALISIB |
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| PIK3CD | 66 | 4 |
| PIK3R1 | 26 | 4 |
| PTEN | 0 | 0 |
Drugs targeting cohort genes (top 30)
| Molecule | Max phase | Targets in cohort |
|---|---|---|
| IDELALISIB | 4 | PIK3CD, PIK3R1 |
| ALPELISIB | 4 | PIK3CD, PIK3R1 |
| DUVELISIB | 4 | PIK3CD, PIK3R1 |
| COPANLISIB | 4 | PIK3CD, PIK3R1 |
| UMBRALISIB | 4 | PIK3CD, PIK3R1 |
| CAFFEINE | 4 | PIK3CD |
| THEOPHYLLINE | 4 | PIK3CD |
| COPANLISIB HYDROCHLORIDE | 4 | PIK3CD |
| LENIOLISIB | 4 | PIK3CD |
| INAVOLISIB | 4 | PIK3CD |
| SUNITINIB | 4 | PIK3CD |
| DASATINIB | 4 | PIK3CD |
| DACTOLISIB | 3 | PIK3CD, PIK3R1 |
| BUPARLISIB | 3 | PIK3CD, PIK3R1 |
| TASELISIB | 3 | PIK3CD |
| PARSACLISIB | 3 | PIK3CD |
| POVORCITINIB | 3 | PIK3CD |
| GEDATOLISIB | 3 | PIK3CD |
| LESTAURTINIB | 3 | PIK3CD |
| QUERCETIN | 3 | PIK3R1 |
| OMIPALISIB | 2 | PIK3CD, PIK3R1 |
| GSK-2636771 | 2 | PIK3CD, PIK3R1 |
| FIMEPINOSTAT | 2 | PIK3CD, PIK3R1 |
| EGANELISIB | 2 | PIK3CD, PIK3R1 |
| AMDIZALISIB | 2 | PIK3CD, PIK3R1 |
| RISOVALISIB | 2 | PIK3CD, PIK3R1 |
| PICTILISIB | 2 | PIK3CD, PIK3R1 |
| ZSTK-474 | 2 | PIK3CD, PIK3R1 |
| PF-04691502 | 2 | PIK3CD |
| IZORLISIB | 2 | PIK3CD |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 3.
Cohort genes with ChEMBL bioactivity (full, sorted by assay count)
| Symbol | Assays | Type breakdown |
|---|---|---|
| PIK3CD | 1,111 | Binding:1094, ADMET:8, Functional:8, Toxicity:1 |
| PIK3R1 | 493 | Binding:470, ADMET:23 |
| PTEN | 8 | Binding:8 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| PIK3CD | 2.7.1.137, 2.7.1.153, 2.7.11.1 | phosphatidylinositol 3-kinase, phosphatidylinositol-4,5-bisphosphate 3-kinase, non-specific serine/threonine protein kinase |
| PIK3R1 | 2.7.1.153 | phosphatidylinositol-4,5-bisphosphate 3-kinase |
| PTEN | 3.1.3.16, 3.1.3.67 | protein-serine/threonine phosphatase, phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase |
Cohort genes with high screening signal
≥100 ChEMBL assays — a studied-ness signal; see Therapeutics for approved-drug status.
| Symbol | ChEMBL assays |
|---|---|
| PIK3CD | 1,111 |
| PIK3R1 | 493 |
Pharmacogenomics
Cohort genes with a PharmGKB record: 3; with CPIC/DPWG dosing guidelines: 0.
No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).
Chemical tractability of cohort targets
29 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.
| Compound | Max phase | Cohort target (bioactivity) |
|---|---|---|
| IDELALISIB | 4 | PIK3CD, PIK3R1 |
| ALPELISIB | 4 | PIK3CD, PIK3R1 |
| DUVELISIB | 4 | PIK3CD, PIK3R1 |
| COPANLISIB | 4 | PIK3CD, PIK3R1 |
| UMBRALISIB | 4 | PIK3CD, PIK3R1 |
| CAFFEINE | 4 | PIK3CD |
| THEOPHYLLINE | 4 | PIK3CD |
| COPANLISIB HYDROCHLORIDE | 4 | PIK3CD |
| INAVOLISIB | 4 | PIK3CD |
| SUNITINIB | 4 | PIK3CD |
| DASATINIB | 4 | PIK3CD |
| DACTOLISIB | 3 | PIK3CD, PIK3R1 |
| BUPARLISIB | 3 | PIK3CD, PIK3R1 |
| TASELISIB | 3 | PIK3CD |
| PARSACLISIB | 3 | PIK3CD |
| POVORCITINIB | 3 | PIK3CD |
| GEDATOLISIB | 3 | PIK3CD |
| LESTAURTINIB | 3 | PIK3CD |
| QUERCETIN | 3 | PIK3R1 |
| OMIPALISIB | 2 | PIK3CD, PIK3R1 |
| GSK-2636771 | 2 | PIK3CD, PIK3R1 |
| FIMEPINOSTAT | 2 | PIK3CD, PIK3R1 |
| EGANELISIB | 2 | PIK3CD, PIK3R1 |
| AMDIZALISIB | 2 | PIK3CD, PIK3R1 |
| RISOVALISIB | 2 | PIK3CD, PIK3R1 |
| PICTILISIB | 2 | PIK3CD, PIK3R1 |
| ZSTK-474 | 2 | PIK3CD, PIK3R1 |
| PF-04691502 | 2 | PIK3CD |
| IZORLISIB | 2 | PIK3CD |
Druggability pyramid
Cohort genes binned by druggability tier (high → low):
| Tier | Definition | Genes | Symbols |
|---|---|---|---|
| A | Approved (phase 4 drug) | 2 | PIK3CD, PIK3R1 |
| B | Phased (≥1) drug, not yet approved | 0 | |
| C | Druggable family + PDB, no drug | 1 | PTEN |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| PTEN | 8 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 5.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| PHASE3 | 2 |
| PHASE2 | 1 |
| PHASE1/PHASE2 | 1 |
| Not specified | 1 |
Top trials by phase / activity
| NCT | 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 |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| LENIOLISIB | 4 | 2 |
| SIROLIMUS | 4 | 1 |
| NEMIRALISIB | 2 | 1 |
| CHEMBL3643409 | 0 | 2 |
Related Atlas pages
- Cohort genes: PIK3CD, PIK3R1, PTEN
- Drugs: Leniolisib, Sirolimus