PIK3R5

Summary

PIK3R5 (phosphoinositide-3-kinase regulatory subunit 5, HGNC:30035) is a protein-coding gene on chromosome 17p13.1, encoding Phosphoinositide 3-kinase regulatory subunit 5 (Q8WYR1). Regulatory subunit of the PI3K gamma complex.

Phosphatidylinositol 3-kinases (PI3Ks) phosphorylate the inositol ring of phosphatidylinositol at the 3-prime position, and play important roles in cell growth, proliferation, differentiation, motility, survival and intracellular trafficking. The PI3Ks are divided into three classes: I, II and III, and only the class I PI3Ks are involved in oncogenesis. This gene encodes the 101 kD regulatory subunit of the class I PI3K gamma complex, which is a dimeric enzyme, consisting of a 110 kD catalytic subunit gamma and a regulatory subunit of either 55, 87 or 101 kD. This protein recruits the catalytic subunit from the cytosol to the plasma membrane through high-affinity interaction with G-beta-gamma proteins. Multiple alternatively spliced transcript variants encoding two distinct isoforms have been found.

Source: NCBI Gene 23533 — RefSeq curated summary.

At a glance

• Gene–disease (curated): spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (Supportive, GenCC) — +1 more curated relationship
• GWAS associations: 5
• Clinical variants (ClinVar): 202 total
• Phenotypes (HPO): 37
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001142633

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30035
Approved symbol	PIK3R5
Name	phosphoinositide-3-kinase regulatory subunit 5
Location	17p13.1
Locus type	gene with protein product
Status	Approved
Aliases	P101-PI3K, p101
Ensembl gene	ENSG00000141506
Ensembl biotype	protein_coding
OMIM	611317
Entrez	23533

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 9 protein_coding, 6 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000269300, ENST00000447110, ENST00000577214, ENST00000577981, ENST00000578457, ENST00000578515, ENST00000578743, ENST00000580959, ENST00000581552, ENST00000581895, ENST00000583039, ENST00000583222, ENST00000583810, ENST00000584456, ENST00000584803, ENST00000585260, ENST00000611902, ENST00000616147, ENST00000623421, ENST00000935159

RefSeq mRNA: 11 — MANE Select: NM_001142633 NM_001142633, NM_001251851, NM_001251852, NM_001251853, NM_001251855, NM_001388396, NM_001388397, NM_001388398, NM_001388399, NM_001388400, NM_014308

CCDS: CCDS11147, CCDS73986, CCDS92257

Canonical transcript exons

ENST00000447110 — 19 exons

Exon	Start	End
ENSE00001732883	8965596	8965707
ENSE00003475774	8904777	8904915
ENSE00003480734	8887096	8887221
ENSE00003497637	8888171	8888891
ENSE00003499805	8886477	8886605
ENSE00003523453	8889973	8890126
ENSE00003540632	8889139	8889222
ENSE00003544890	8881630	8881712
ENSE00003545380	8881788	8881881
ENSE00003559638	8890738	8890912
ENSE00003582925	8893586	8893655
ENSE00003609406	8886229	8886322
ENSE00003611364	8909074	8909174
ENSE00003626439	8880905	8881017
ENSE00003653688	8884707	8884783
ENSE00003675014	8887521	8887683
ENSE00003683111	8911392	8911507
ENSE00003687716	8905669	8905737
ENSE00003735902	8878916	8880786

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 97.91.

FANTOM5 (CAGE): breadth broad, TPM avg 21.2863 / max 1472.0347, expressed in 618 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
164489	20.9447	614
164491	0.1609	77
164490	0.1286	68
164459	0.0471	21
164460	0.0049	1

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	97.91	gold quality
blood	UBERON:0000178	96.12	gold quality
monocyte	CL:0000576	95.10	gold quality
leukocyte	CL:0000738	94.92	gold quality
mononuclear cell	CL:0000842	94.79	gold quality
spleen	UBERON:0002106	90.80	gold quality
bone marrow cell	CL:0002092	88.50	gold quality
upper lobe of left lung	UBERON:0008952	88.19	gold quality
bone marrow	UBERON:0002371	87.39	gold quality
upper lobe of lung	UBERON:0008948	87.17	gold quality
lymph node	UBERON:0000029	86.51	gold quality
right lung	UBERON:0002167	86.04	gold quality
vermiform appendix	UBERON:0001154	85.92	gold quality
caecum	UBERON:0001153	82.37	gold quality
small intestine Peyer’s patch	UBERON:0003454	82.23	gold quality
gall bladder	UBERON:0002110	81.86	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.30	gold quality
right adrenal gland cortex	UBERON:0035827	79.88	gold quality
omental fat pad	UBERON:0010414	79.86	gold quality
peritoneum	UBERON:0002358	79.82	gold quality
trabecular bone tissue	UBERON:0002483	79.76	gold quality
small intestine	UBERON:0002108	79.57	gold quality
adipose tissue of abdominal region	UBERON:0007808	79.21	gold quality
right adrenal gland	UBERON:0001233	78.44	gold quality
left adrenal gland	UBERON:0001234	78.38	gold quality
right coronary artery	UBERON:0001625	78.11	gold quality
lung	UBERON:0002048	77.99	gold quality
left adrenal gland cortex	UBERON:0035825	77.81	gold quality
left uterine tube	UBERON:0001303	77.69	gold quality
adrenal cortex	UBERON:0001235	77.53	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-119	yes	6.51
E-MTAB-5061	no	3.86
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F1

miRNA regulators (miRDB)

70 targeting PIK3R5, 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-6867-5P	100.00	82.21	3464
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-4671-3P	99.88	72.46	1045
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-7856-5P	99.75	69.99	2901
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-762	99.58	66.61	1994
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-6740-3P	99.48	68.49	1392
HSA-MIR-4498	99.47	67.42	2360
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-6809-5P	99.13	68.45	1223

Literature-anchored findings (GeneRIF, showing 11)

• p101 has a role in membrane recruitment and activation of PI3K gamma (PMID:12507995)
• analysis of functional domains in the p101 regulatory subunit of phosphoinositide 3-kinase gamma (PMID:15611065)
• Overexpression of p101 activates PI3Kgamma signaling and is associated with T-cell lymphomas (PMID:17486067)
• Our characterization of the PIK3R5 protein and findings suggest that it may play a role in the development of the cerebellum and vermis. (PMID:22065524)
• expression and activities of PI3Kgamma are modified differently by p87 and p101 in vitro and in living cells, arguing for specific regulatory roles of the non-catalytic subunits in the differentiation of PI3Kgamma signaling pathways. (PMID:24014027)
• PIK3R5 promoter hypermethylation is associated with oral squamous cell carcinoma. (PMID:25374236)
• data argue for differential regulatory functions of the non-catalytic subunits and a specific Gbetagamma-dependent regulation of p101 in PI3Kgamma activation. (PMID:26173259)
• G protein betagamma translocation to the Golgi apparatus activates MAPK via p110gamma-p101 heterodimers. (PMID:33493514)
• HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression. (PMID:34187569)
• PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors. (PMID:34775477)
• Targetable leukaemia dependency on noncanonical PI3Kgamma signalling. (PMID:38720074)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pik3r5	ENSDARG00000102762
mus_musculus	Pik3r5	ENSMUSG00000020901
rattus_norvegicus	Pik3r5	ENSRNOG00000023428

Paralogs (1): PIK3R6 (ENSG00000276231)

Protein

Protein identifiers

Phosphoinositide 3-kinase regulatory subunit 5 — Q8WYR1 (reviewed: Q8WYR1)

Alternative names: PI3-kinase p101 subunit, Phosphatidylinositol 4,5-bisphosphate 3-kinase regulatory subunit, Protein FOAP-2, PtdIns-3-kinase p101, p101-PI3K

All UniProt accessions (6): Q8WYR1, J3KRE9, J3KSW1, J3KT66, L7RT34, X6R3K3

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the PI3K gamma complex. Required for recruitment of the catalytic subunit to the plasma membrane via interaction with beta-gamma G protein dimers. Required for G protein-mediated activation of PIK3CG.

Subunit / interactions. Heterodimer of a catalytic subunit (PIK3CG/p120) and a regulatory (PIK3R5a/p101) subunit. Interacts with beta-gamma G protein dimers.

Subcellular location. Nucleus. Cytoplasm. Cell membrane.

Tissue specificity. Ubiquitously expressed with high expression in fetal brain compared to adult brain. Abundant expression is observed in cerebellum, cerebral cortex, cerebral meninges, and vermis cerebelli.

Disease relevance. Ataxia-oculomotor apraxia 3 (AOA3) [MIM:615217] An autosomal recessive disease characterized by cerebellar ataxia, oculomotor apraxia, areflexia and peripheral neuropathy. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Greatly activated by G gamma proteins.

Domain organisation. The heterodimerization region allows the binding to the catalytic subunit.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8WYR1-1	1	yes
Q8WYR1-2	2

RefSeq proteins (11): NP_001136105, NP_001238780, NP_001238781, NP_001238782, NP_001238784, NP_001375325, NP_001375326, NP_001375327, NP_001375328, NP_001375329, NP_055123 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019522	PIK3R5/6	Family

Pfam: PF10486

UniProt features (23 total): sequence conflict 8, region of interest 6, modified residue 3, sequence variant 2, compositionally biased region 2, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WYR1-F1	71.39	0.47

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 (3): 458, 507, 1

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
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-392451	G beta:gamma signalling through PI3Kgamma
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-9027276	Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-9927354	Co-stimulation by ICOS

MSigDB gene sets: 371 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_REGULATION_OF_PHOSPHORYLATION, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, XU_HGF_TARGETS_REPRESSED_BY_AKT1_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, REACTOME_CO_STIMULATION_BY_CD28, GOCC_MICROTUBULE_ORGANIZING_CENTER, EFC_Q6, KEGG_FC_EPSILON_RI_SIGNALING_PATHWAY, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (6): immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of MAP kinase activity (GO:0043406), phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0043491), phosphatidylinositol metabolic process (GO:0046488), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897)

GO Molecular Function (3): G-protein beta/gamma-subunit complex binding (GO:0031683), 1-phosphatidylinositol-3-kinase regulator activity (GO:0046935), kinase activity (GO:0016301)

GO Cellular Component (9): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), phosphatidylinositol 3-kinase complex (GO:0005942), phosphatidylinositol 3-kinase complex, class IA (GO:0005943), phosphatidylinositol 3-kinase complex, class IB (GO:0005944), membrane (GO:0016020), centriolar satellite (GO:0034451)

Reactome top-level categories

Rollup of top-9 pathways:

Category	Pathways
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
PI Metabolism	1
PI3K/AKT Signaling in Cancer	1
Co-stimulation by CD28	1
G-protein beta:gamma signalling	1
Negative regulation of the PI3K/AKT network	1
Signaling by Erythropoietin	1
Regulation of T cell activation by CD28 family	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphatidylinositol 3-kinase complex, class I	2
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
MAP kinase activity	1
regulation of MAP kinase activity	1
positive regulation of MAPK cascade	1
positive regulation of protein serine/threonine kinase activity	1
intracellular signaling cassette	1
phosphorus metabolic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
positive regulation of intracellular signal transduction	1
protein-containing complex binding	1
1-phosphatidylinositol-3-kinase activity	1
kinase regulator activity	1
transferase activity, transferring phosphorus-containing groups	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
extrinsic component of membrane	1
transferase complex, transferring phosphorus-containing groups	1
membrane protein complex	1
centrosome	1

Protein interactions and networks

STRING

1354 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIK3R5	PIK3CG	P48736	998
PIK3R5	PIK3CA	P42336	992
PIK3R5	PIK3CD	O00329	990
PIK3R5	PIK3CB	P42338	990
PIK3R5	IMMT	Q16891	854
PIK3R5	PIK3R3	Q92569	824
PIK3R5	PIK3R2	O00459	817
PIK3R5	PPP1R12C	Q9BZL4	774
PIK3R5	SUCLG2	Q96I99	762
PIK3R5	GNG2	P59768	760
PIK3R5	GNB1	P04697	720
PIK3R5	PIK3R1	P27986	673
PIK3R5	PDE3B	Q13370	659
PIK3R5	PIK3C3	Q8NEB9	611
PIK3R5	PTEN	P60484	605

IntAct

9 interactions, top by confidence:

A	B	Type	Score
CFTR	PIK3R5	psi-mi:“MI:0915”(physical association)	0.370
PIK3R5	PIK3CG	psi-mi:“MI:2364”(proximity)	0.270
PIK3R5	SDHB	psi-mi:“MI:0915”(physical association)	0.000
PIK3R5	CXCL2	psi-mi:“MI:0915”(physical association)	0.000
PIK3R5	TTR	psi-mi:“MI:0915”(physical association)	0.000
PIK3R5	CYP4A11	psi-mi:“MI:0915”(physical association)	0.000
ADAMTS2	PIK3R5	psi-mi:“MI:0915”(physical association)	0.000
PIK3R5	acn	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (17): PIK3CG (Phenotypic Enhancement), GNB1 (Phenotypic Enhancement), GNG2 (Phenotypic Enhancement), PIK3R5 (Phenotypic Enhancement), PIK3CG (Co-localization), PIK3R5 (Affinity Capture-Western), PIK3R5 (FRET), PIK3R5 (Reconstituted Complex), PIK3CG (FRET), PIK3CG (Co-fractionation), PIK3CG (Co-localization), PIK3R5 (PCA), PIK3R5 (Cross-Linking-MS (XL-MS)), PIK3R5 (Affinity Capture-MS), PIK3R5 (Protein-peptide)

ESM2 similar proteins: A1A4J7, A2A9C3, A2BID5, B1WC10, E7FAW3, E7FCN8, O02696, O15360, O75153, O75800, O95248, Q08D69, Q1JPG0, Q3U6Q4, Q499Q5, Q5BLE2, Q5SW28, Q5SW45, Q5T011, Q5U1Z0, Q5U249, Q5UE93, Q5ZIB8, Q6AXZ5, Q6GLY5, Q6GR21, Q6PGF3, Q6ZNJ1, Q6ZQA0, Q7L4E1, Q8BK03, Q8BM55, Q8BMG7, Q8C3S2, Q8CJF7, Q8ND04, Q8QZV7, Q8TC57, Q8VDR9, Q8VE18

Diamond homologs: O02696, Q5SW28, Q5ZIB8, Q6INI0, Q8WYR1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	122
Likely benign	23
Benign	18

Top pathogenic / likely-pathogenic (0)

SpliceAI

3614 predictions. Top by Δscore:

Variant	Effect	Δscore
17:8881013:CTAAT:C	acceptor_gain	1.0000
17:8881014:TAAT:T	acceptor_gain	1.0000
17:8881016:AT:A	acceptor_gain	1.0000
17:8881017:TCTG:T	acceptor_loss	1.0000
17:8881018:C:CC	acceptor_gain	1.0000
17:8881019:T:C	acceptor_loss	1.0000
17:8881629:C:A	donor_loss	1.0000
17:8881782:ACTC:A	donor_loss	1.0000
17:8881783:CTCA:C	donor_loss	1.0000
17:8881784:TCACC:T	donor_loss	1.0000
17:8881785:CAC:C	donor_loss	1.0000
17:8881786:AC:A	donor_gain	1.0000
17:8881786:ACCCA:A	donor_loss	1.0000
17:8881787:CC:C	donor_gain	1.0000
17:8881787:CCCAG:C	donor_gain	1.0000
17:8881796:T:TA	donor_gain	1.0000
17:8881803:T:TA	donor_gain	1.0000
17:8886224:CCCA:C	donor_loss	1.0000
17:8886227:A:C	donor_loss	1.0000
17:8886318:GTCAG:G	acceptor_gain	1.0000
17:8886319:TCAG:T	acceptor_gain	1.0000
17:8886320:CAG:C	acceptor_gain	1.0000
17:8886320:CAGC:C	acceptor_gain	1.0000
17:8886321:AG:A	acceptor_gain	1.0000
17:8886322:GCT:G	acceptor_loss	1.0000
17:8886323:C:CA	acceptor_loss	1.0000
17:8886323:C:CC	acceptor_gain	1.0000
17:8886324:T:A	acceptor_loss	1.0000
17:8886333:C:CT	acceptor_gain	1.0000
17:8886471:CCTTA:C	donor_loss	1.0000

AlphaMissense

5678 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:8888231:A:T	V519D	0.997
17:8887152:A:G	W617R	0.996
17:8887152:A:T	W617R	0.996
17:8909147:A:G	L44P	0.996
17:8888192:G:T	A532D	0.995
17:8889157:A:G	W293R	0.995
17:8889157:A:T	W293R	0.995
17:8909138:A:G	L47P	0.995
17:8909149:G:C	S43R	0.995
17:8909149:G:T	S43R	0.995
17:8909151:T:G	S43R	0.995
17:8909154:A:G	W42R	0.995
17:8909154:A:T	W42R	0.995
17:8911457:A:G	I13T	0.995
17:8911460:C:G	R12P	0.995
17:8911461:G:T	R12S	0.995
17:8888234:C:G	R518P	0.994
17:8890901:A:G	L165P	0.994
17:8911445:A:G	L17P	0.994
17:8911457:A:C	I13S	0.994
17:8880673:A:G	L870P	0.993
17:8884726:A:G	L729P	0.993
17:8886514:G:T	A666D	0.993
17:8886520:C:G	R664P	0.993
17:8887149:A:C	Y618D	0.993
17:8888174:A:G	L538P	0.993
17:8881820:A:G	L756P	0.992
17:8888187:C:G	A534P	0.992
17:8888189:C:G	R533P	0.992
17:8888237:A:G	L517P	0.992

dbSNP variants (sampled 300 via entrez): RS1000031536 (17:8892269 G>T), RS1000034950 (17:8920801 G>C,T), RS1000048618 (17:8967111 C>A), RS1000089843 (17:8941264 C>T), RS1000117482 (17:8955450 A>C), RS1000123559 (17:8932383 C>T), RS1000143227 (17:8879559 G>A), RS1000157184 (17:8937920 C>T), RS1000167725 (17:8897342 C>A,G), RS1000172478 (17:8897080 C>T), RS1000220914 (17:8951272 C>A,T), RS1000331109 (17:8904569 C>T), RS1000331733 (17:8955803 A>G), RS1000337120 (17:8943226 T>C), RS1000362275 (17:8903116 A>G)

Disease associations

OMIM: gene MIM:611317 | disease phenotypes: MIM:108600, MIM:615217

GenCC curated gene-disease

Disease	Classification	Inheritance
spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	Supportive	Autosomal recessive
ataxia with oculomotor apraxia type 3	Limited	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ataxia with oculomotor apraxia type 3	Disputed	AR

Mondo (3): spastic ataxia (MONDO:0017845), ataxia with oculomotor apraxia type 3 (MONDO:0014084), spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 (MONDO:0018996)

Orphanet (2): Spastic ataxia (Orphanet:316226), Spinocerebellar ataxia with axonal neuropathy type 2 (Orphanet:64753)

HPO phenotypes

37 total (30 of 37 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000486	Strabismus
HP:0000514	Slow saccadic eye movements
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000657	Oculomotor apraxia
HP:0001152	Saccadic smooth pursuit interruptions
HP:0001251	Ataxia
HP:0001260	Dysarthria
HP:0001265	Hyporeflexia
HP:0001266	Choreoathetosis
HP:0001272	Cerebellar atrophy
HP:0001284	Areflexia
HP:0001310	Dysmetria
HP:0001324	Muscle weakness
HP:0001332	Dystonia
HP:0002015	Dysphagia
HP:0002141	Gait imbalance
HP:0002174	Postural tremor
HP:0002346	Head tremor
HP:0002359	Frequent falls
HP:0002839	Urinary bladder sphincter dysfunction
HP:0002936	Distal sensory impairment
HP:0003073	Hypoalbuminemia
HP:0003124	Hypercholesterolemia
HP:0003236	Elevated circulating creatine kinase concentration
HP:0003474	Somatic sensory dysfunction
HP:0003477	Peripheral axonal neuropathy
HP:0003487	Babinski sign
HP:0003621	Juvenile onset

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST008098_2	Atypical femoral fracture in phosphonate treatment	5.000000e-06
GCST010571_67	Autoimmune thyroid disease	4.000000e-10
GCST90002381_111	Eosinophil count	4.000000e-11
GCST90002382_414	Eosinophil percentage of white cells	4.000000e-12
GCST90002394_514	Monocyte percentage of white cells	8.000000e-10

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009958	response to bisphosphonate
EFO:0009960	atypical femoral fracture
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564815	Spastic Ataxia (supp.)
C537308	Spinocerebellar ataxia, autosomal recessive 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3430881 (PROTEIN COMPLEX), CHEMBL3559703 (PROTEIN COMPLEX GROUP)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 20,694 (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
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL2017974	BUPARLISIB	3	6,568
CHEMBL521851	PICTILISIB	2	6,071
CHEMBL3683575	ROGINOLISIB	2	67

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs444904	Toxicity	3	sorafenib	Hypertension

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs444904	PIK3R5	3	1.50	1	sorafenib

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

Binding affinities (BindingDB)

26 measured of 26 human assays (27 total across all organisms); most potent 26 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-4-{2-[4-(trifluoromethyl)phenyl]ethyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	1.92 nM
4-[2-(4-bromophenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	2.34 nM
4-[(4-tert-butylphenyl)methyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	2.42 nM
4-[(3,4-dimethylphenyl)methyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	2.59 nM
4-[2-(3,5-dimethylphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	2.65 nM
4-[2-(3-methoxyphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	2.66 nM
4-[2-(3,5-dimethoxyphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	2.79 nM
4-[2-(3-chlorophenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	4.27 nM
4-[2-(2,4-dichlorophenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	4.28 nM
4-[2-(3,4-dichlorophenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	4.36 nM
4-[2-(4-chlorophenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	4.76 nM
4-[2-(3,4-difluorophenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	4.84 nM
4-[2-(3-methylphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	4.96 nM
(2R,3S,6Z,14S,15S,17R)-6-({3-(dimethylamino)propylamino}methylidene)-8,14-dihydroxy-3-(methoxymethyl)-2,15-dimethyl-5,9-dioxo-4-oxatetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-1(10),7-dien-17-yl acetate	IC50	6.4 nM
4-[2-(4-methoxyphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	6.57 nM
4-[(4-chlorophenyl)methyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	7.16 nM
4-[2-(4-methylphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	8.83 nM
4-benzyl-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	23 nM
6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-4-(2-phenylethyl)-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	24.5 nM
6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-4-{[4-(trifluoromethyl)phenyl]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	27.5 nM
4-[(4-methylphenyl)methyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	29.5 nM
4-[2-(4-tert-butylphenyl)ethyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	33.2 nM
4-[(3-oxo-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-4-yl)methyl]benzonitrile	IC50	36.1 nM
4-[(3-methylphenyl)methyl]-6-{[(5Z)-4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene]methyl}-3,4-dihydro-2H-1,4-benzoxazin-3-one	IC50	43.7 nM
(5Z)-5-[(3-hydroxy-5-methoxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	IC50	77.7 nM
2-(4-Morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	IC50	13100 nM	US-9505780: Thienopyranones as kinase and epigenetic inhibitors

ChEMBL bioactivities

430 potent at pChembl≥5 of 440 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.22	IC50	6	nM	CHEMBL3683580
8.15	IC50	7	nM	CHEMBL3683671
7.96	IC50	11	nM	CHEMBL3612310
7.96	IC50	11	nM	CHEMBL3683555
7.89	IC50	13	nM	CHEMBL3683606
7.89	IC50	13	nM	CHEMBL3683649
7.89	IC50	13	nM	CHEMBL3683695
7.85	IC50	14	nM	CHEMBL3683596
7.85	IC50	14	nM	CHEMBL3683693
7.82	IC50	15	nM	CHEMBL3683611
7.82	IC50	15	nM	CHEMBL3683686
7.80	IC50	16	nM	CHEMBL3683556
7.80	IC50	16	nM	CHEMBL3683584
7.80	IC50	16	nM	CHEMBL3683641
7.80	IC50	16	nM	CHEMBL3683644
7.77	IC50	17	nM	CHEMBL3683594
7.75	IC50	18	nM	CHEMBL3683680
7.75	IC50	18	nM	CHEMBL3683684
7.72	IC50	19	nM	CHEMBL3683613
7.70	IC50	20	nM	CHEMBL3683667
7.70	IC50	20	nM	CHEMBL3683675
7.68	IC50	21	nM	CHEMBL3683552
7.68	IC50	21	nM	CHEMBL3683632
7.68	IC50	21	nM	CHEMBL3683681
7.66	IC50	22	nM	CHEMBL3683530
7.66	IC50	22	nM	CHEMBL3683685
7.62	IC50	24	nM	CHEMBL3683612
7.62	IC50	24	nM	CHEMBL3683617
7.60	IC50	25	nM	CHEMBL3683593
7.60	IC50	25	nM	CHEMBL3683595
7.60	IC50	25	nM	CHEMBL3683647
7.60	IC50	25	nM	CHEMBL3683661
7.60	IC50	25	nM	CHEMBL3683690
7.57	IC50	27	nM	CHEMBL3683600
7.55	IC50	28	nM	CHEMBL3683672
7.55	IC50	28	nM	CHEMBL3683674
7.54	IC50	29	nM	CHEMBL3683548
7.54	IC50	29	nM	CHEMBL3683614
7.52	IC50	30	nM	CHEMBL3683615
7.51	IC50	31	nM	CHEMBL3683656
7.50	IC50	32	nM	CHEMBL3683599
7.47	IC50	34	nM	CHEMBL3683531
7.47	IC50	34	nM	CHEMBL3683533
7.47	IC50	34	nM	CHEMBL3683556
7.47	IC50	34	nM	CHEMBL3683666
7.44	IC50	36	nM	CHEMBL3683523
7.44	IC50	36	nM	CHEMBL3683610
7.42	IC50	38	nM	CHEMBL3683551
7.42	IC50	38	nM	CHEMBL3683642
7.41	IC50	39	nM	CHEMBL3683651

PubChem BioAssay actives

38 with measured affinity, of 38 total; 37 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
6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-4-[2-[4-(trifluoromethyl)phenyl]ethyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0019	uM
4-[2-(4-bromophenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0023	uM
4-[(4-tert-butylphenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0024	uM
4-[(3,4-dimethylphenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0026	uM
4-[2-(3,5-dimethylphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0027	uM
4-[2-(3-methoxyphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0027	uM
4-[2-(3,5-dimethoxyphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0028	uM
4-[2-(3-chlorophenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0043	uM
4-[2-(2,4-dichlorophenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0043	uM
4-[2-(3,4-dichlorophenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0044	uM
4-[2-(4-chlorophenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0048	uM
4-[2-(3,4-difluorophenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0048	uM
4-[2-(3-methylphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0050	uM
4-[2-(4-methoxyphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0066	uM
4-[(4-chlorophenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0072	uM
[(1S,6Z,9S,9aS,10R,11aS)-6-[[3-(dimethylamino)propyl-methylamino]methylidene]-1-hydroxy-9-(methoxymethyl)-9a,11a-dimethyl-4,5,7-trioxo-1,2,3,3a,5a,9,10,11-octahydroindeno[4,5-h]isochromen-10-yl] acetate	1798030: PI3K Inhibition Assay from Article 10.1021/jm7012858: “Synthesis and structure-activity relationships of ring-opened 17-hydroxywortmannins: potent phosphoinositide 3-kinase inhibitors with improved properties and anticancer efficacy.”	ic50	0.0080	uM
4-[2-(4-methylphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0088	uM
1-[2-(diethylamino)ethyl]-3-[6-[5-[(4-fluorophenyl)sulfonylamino]-6-methoxy-3-pyridinyl]-1,3-benzothiazol-2-yl]urea	1245325: Inhibition of p110gamma/PIK3R5 (unknown origin) incubated for 40 mins by luciferase based ATP depletion assay	ic50	0.0110	uM
[(1R,3R,5S,9R,18S)-18-(methoxymethyl)-1,5-dimethyl-6,11,16-trioxo-13,17-dioxapentacyclo[10.6.1.02,10.05,9.015,19]nonadeca-2(10),12(19),14-trien-3-yl] acetate	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0190	uM
4-benzyl-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0230	uM
6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-4-(2-phenylethyl)-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0245	uM
6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-4-[[4-(trifluoromethyl)phenyl]methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0275	uM
4-[(4-methylphenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0295	uM
4-[2-(4-tert-butylphenyl)ethyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0332	uM
4-[[3-oxo-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-4-yl]methyl]benzonitrile	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0361	uM
4-[(3-methylphenyl)methyl]-6-[(Z)-(4-oxo-2-sulfanylidene-1,3-thiazolidin-5-ylidene)methyl]-1,4-benzoxazin-3-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0437	uM
2-methyl-2-[4-(3-methyl-2-oxo-8-quinolin-3-ylimidazo[4,5-c]quinolin-1-yl)phenyl]propanenitrile	1245325: Inhibition of p110gamma/PIK3R5 (unknown origin) incubated for 40 mins by luciferase based ATP depletion assay	ic50	0.0720	uM
(5Z)-5-[(3-hydroxy-5-methoxyphenyl)methylidene]-2-sulfanylidene-1,3-thiazolidin-4-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	0.0777	uM
[4-[[4-[6-amino-4-(trifluoromethyl)-3-pyridinyl]-6-morpholin-4-ylpyrimidin-2-yl]amino]phenyl]-(4-methylsulfonylpiperazin-1-yl)methanone	1628743: Inhibition of PI3K p110gamma/p101 (unknown origin) using PIP2/ATP as substrate after 1 hr by kinase glo luminescent assay	ic50	0.0800	uM
N-[5-[3-[(3S)-1-(cyclopropanecarbonyl)pyrrolidin-3-yl]-4-oxoquinazolin-6-yl]-2-methoxy-3-pyridinyl]-4-fluorobenzenesulfonamide	1433190: Inhibition of P110gamma/PIK3R5 (unknown origin) using L-alpha-phosphatidylinositol as substrate after 40 mins by ATP depletion assay	ic50	0.1160	uM
4-[2-(1H-indazol-4-yl)-6-[(4-methylsulfonylpiperazin-1-yl)methyl]thieno[3,2-d]pyrimidin-4-yl]morpholine	1202631: Inhibition of p110gamma/PIK3R5 (unknown origin) using L-alpha-phosphatidylinositol incubated for 40 mins by ADP depletion detection based luciferase assay	ic50	0.1170	uM
5-(2,6-dimorpholin-4-ylpyrimidin-4-yl)-4-(trifluoromethyl)pyridin-2-amine	1628743: Inhibition of PI3K p110gamma/p101 (unknown origin) using PIP2/ATP as substrate after 1 hr by kinase glo luminescent assay	ic50	0.1290	uM
5-[2-[(4aS,7aS)-2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrol-6-yl]-6-morpholin-4-ylpyrimidin-4-yl]-4-(trifluoromethyl)pyridin-2-amine	1628743: Inhibition of PI3K p110gamma/p101 (unknown origin) using PIP2/ATP as substrate after 1 hr by kinase glo luminescent assay	ic50	0.1580	uM
N-[5-[3-[(3S)-1-(cyclopropylmethyl)pyrrolidin-3-yl]-4-oxoquinazolin-6-yl]-2-methoxy-3-pyridinyl]-4-fluorobenzenesulfonamide	1433190: Inhibition of P110gamma/PIK3R5 (unknown origin) using L-alpha-phosphatidylinositol as substrate after 40 mins by ATP depletion assay	ic50	0.1810	uM
3-(6,7-dimethoxy-4-morpholin-4-ylquinazolin-2-yl)-5-hydroxybenzamide	1202631: Inhibition of p110gamma/PIK3R5 (unknown origin) using L-alpha-phosphatidylinositol incubated for 40 mins by ADP depletion detection based luciferase assay	ic50	0.3940	uM
3-(6,7-dimethoxy-4-morpholin-4-ylquinazolin-2-yl)-5-(trifluoromethoxy)benzamide	1202631: Inhibition of p110gamma/PIK3R5 (unknown origin) using L-alpha-phosphatidylinositol incubated for 40 mins by ADP depletion detection based luciferase assay	ic50	0.4650	uM
2-morpholin-4-yl-8-phenylchromen-4-one	1798510: PI3Kgamma Inhibition Assay from Article 10.1016/j.bmcl.2006.10.080: “Design and synthesis of phenethyl benzo[1,4]oxazine-3-ones as potent inhibitors of PI3Kinasegamma.”	ic50	1.7200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases expression, increases methylation	3
Tobacco Smoke Pollution	decreases methylation, increases expression, increases methylation	3
Valproic Acid	decreases methylation, increases expression	3
mercuric bromide	decreases expression, affects cotreatment	2
Phenylmercuric Acetate	decreases expression, affects cotreatment	2
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	decreases expression	1
bisphenol A	decreases methylation	1
ochratoxin A	decreases expression	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Fulvestrant	decreases methylation	1
Air Pollutants	affects expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Benzene	increases expression	1
Calcitriol	decreases expression	1
Copper	affects binding, increases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1
Nickel	increases expression	1
Oligomycins	affects response to substance, decreases expression	1
Ozone	affects expression, increases abundance	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3418084	Binding	Inhibition of p110gamma/PIK3R5 (unknown origin) using L-alpha-phosphatidylinositol incubated for 40 mins by ADP depletion detection based luciferase assay	Synthesis and antitumor activities evaluation of m-(4-morpholinoquinazolin-2-yl)benzamides in vitro and in vivo. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D8SV	Ubigene HCT 116 PIK3R5 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04297891	Not specified	UNKNOWN	Phenotypes, Biomarkers and Pathophysiology in Spastic Ataxias