ITPKA

Summary

ITPKA (inositol-trisphosphate 3-kinase A, HGNC:6178) is a protein-coding gene on chromosome 15q15.1, encoding Inositol-trisphosphate 3-kinase A (P23677). Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.

Regulates inositol phosphate metabolism by phosphorylation of second messenger inositol 1,4,5-trisphosphate to Ins(1,3,4,5)P4. The activity of the inositol 1,4,5-trisphosphate 3-kinase is responsible for regulating the levels of a large number of inositol polyphosphates that are important in cellular signaling. Both calcium/calmodulin and protein phosphorylation mechanisms control its activity. It is also a substrate for the cyclic AMP-dependent protein kinase, calcium/calmodulin- dependent protein kinase II, and protein kinase C in vitro.

Source: NCBI Gene 3706 — RefSeq curated summary.

At a glance

• GWAS associations: 20
• Clinical variants (ClinVar): 64 total
• Druggable target: yes
• MANE Select transcript: NM_002220

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6178
Approved symbol	ITPKA
Name	inositol-trisphosphate 3-kinase A
Location	15q15.1
Locus type	gene with protein product
Status	Approved
Aliases	IP3KA, IP3-3KA
Ensembl gene	ENSG00000137825
Ensembl biotype	protein_coding
OMIM	147521
Entrez	3706

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 retained_intron

ENST00000260386, ENST00000425927, ENST00000462816, ENST00000491007, ENST00000967240

RefSeq mRNA: 1 — MANE Select: NM_002220 NM_002220

CCDS: CCDS10076

Canonical transcript exons

ENST00000260386 — 7 exons

Exon	Start	End
ENSE00000931025	41501463	41501559
ENSE00000931030	41502963	41503551
ENSE00001206292	41493874	41494416
ENSE00003462029	41502788	41502859
ENSE00003489921	41501997	41502201
ENSE00003517628	41502402	41502503
ENSE00003632253	41501635	41501851

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 94.20.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2233 / max 111.2627, expressed in 461 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
146189	1.3194	273
146188	0.8137	284
146190	0.0528	29
146191	0.0372	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	94.20	gold quality
right frontal lobe	UBERON:0002810	93.73	gold quality
Brodmann (1909) area 9	UBERON:0013540	93.05	gold quality
prefrontal cortex	UBERON:0000451	92.59	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	91.54	gold quality
caudate nucleus	UBERON:0001873	90.58	gold quality
middle temporal gyrus	UBERON:0002771	90.58	gold quality
frontal cortex	UBERON:0001870	90.33	gold quality
putamen	UBERON:0001874	90.19	gold quality
cingulate cortex	UBERON:0003027	89.65	gold quality
anterior cingulate cortex	UBERON:0009835	89.38	gold quality
neocortex	UBERON:0001950	89.18	gold quality
nucleus accumbens	UBERON:0001882	89.00	gold quality
Brodmann (1909) area 46	UBERON:0006483	88.00	gold quality
cerebral cortex	UBERON:0000956	87.48	gold quality
telencephalon	UBERON:0001893	87.05	gold quality
superior frontal gyrus	UBERON:0002661	86.82	gold quality
primary visual cortex	UBERON:0002436	86.26	gold quality
amygdala	UBERON:0001876	85.47	gold quality
orbitofrontal cortex	UBERON:0004167	84.11	gold quality
temporal lobe	UBERON:0001871	83.70	gold quality
postcentral gyrus	UBERON:0002581	83.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.46	gold quality
Brodmann (1909) area 23	UBERON:0013554	82.33	gold quality
entorhinal cortex	UBERON:0002728	82.10	gold quality
Brodmann (1909) area 10	UBERON:0013541	81.96	gold quality
forebrain	UBERON:0001890	81.67	gold quality
transverse colon	UBERON:0001157	81.52	gold quality
parietal lobe	UBERON:0001872	81.40	gold quality
Ammon’s horn	UBERON:0001954	81.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.83

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

13 targeting ITPKA, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-9851-3P	99.63	69.68	1110
HSA-MIR-122B-5P	99.46	70.81	1457
HSA-MIR-593-5P	99.34	69.50	965
HSA-MIR-511-5P	98.97	70.94	2268
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-6830-3P	98.62	68.07	1760
HSA-MIR-5088-3P	98.29	66.63	1310
HSA-MIR-8081	96.42	67.75	738
HSA-MIR-9900	96.06	65.48	557
HSA-MIR-3655	86.11	61.77	117

Literature-anchored findings (GeneRIF, showing 15)

• results highlight the potential role of the three isoforms of InsP3 3-kinase as direct InsP3 metabolizing enzymes and direct regulators of Ca2+ responses to extracellular signals (PMID:12747803)
• We report the structure of an IPK, the human Ins(1,4,5)P3 3-kinase-A, both free and in complexes with substrates and products. (PMID:15350214)
• Data suggest that ITPKA may be related to carcinogenesis by the modulation of inositol polyphosphates and Ca2+ homeostasis and that ITPKA may be a potential novel molecular target and biomarker. (PMID:16525636)
• the morphological changes induced by IP3K-A are mediated by non-enzymatic activities of the protein. (PMID:18498254)
• Inositol 1,4,5-trisphosphate 3-kinase-A is a new cell motility-promoting protein that increases the metastatic potential of tumor cells by two functional activities. (PMID:20022963)
• we conclude that the observed expression of ITPKA early in tumor development increases the metastatic potential of lung adenocarcinoma cells. (PMID:21792881)
• describe the crystal structure of the complex between human Ca2+/CaM and the CaM-binding region of human IP3-3K isoform A (residues 158-183) (PMID:25101901)
• Our data indicated that ITPKA expression was significantly up-regulated in hepatocellular carcinoma and could serve as a potential novel prognostic biomarker (PMID:26249031)
• ITPKA is a potential oncogene that it is overexpressed in most tumors, and its overexpression promotes tumorigenesis; ITPKA gene body methylation regulates its expression and serves as a novel and potential biomarker for early cancer detection (PMID:27234602)
• IP3K-A binds to EB3 and their binding affinity is precisely regulated by protein kinase A (PKA)-dependent phosphorylation of IP3K-A at Ser119 (pSer119). The complex of IP3K-A and EB3 dissociates and reassociates rapidly during chemically induced LTP. (PMID:30466786)
• TFAP2A Induced ITPKA Serves as an Oncogene and Interacts with DBN1 in Lung Adenocarcinoma. (PMID:32015686)
• Relationship of ITPKA expression with the prognosis of breast cancer. (PMID:33624455)
• ITPKA induces cell senescence, inhibits ovarian cancer tumorigenesis and can be downregulated by miR-203. (PMID:33879633)
• The actin bundling activity of ITPKA mainly accounts for its migration-promoting effect in lung cancer cells. (PMID:36688944)
• Commentary on: The actin bundling activity of ITPKA mainly accounts for its migration-promoting effect in lung cancer cells. (PMID:37664985)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	itpka	ENSDARG00000042856
mus_musculus	Itpka	ENSMUSG00000027296
rattus_norvegicus	Itpka	ENSRNOG00000005284
drosophila_melanogaster	IP3K1	FBGN0032147
drosophila_melanogaster	Ip6k	FBGN0034644
caenorhabditis_elegans	lfe-2	WBGENE00002979
caenorhabditis_elegans	F30A10.3	WBGENE00009262

Paralogs (6): IP6K2 (ENSG00000068745), ITPKC (ENSG00000086544), ITPKB (ENSG00000143772), IPMK (ENSG00000151151), IP6K3 (ENSG00000161896), IP6K1 (ENSG00000176095)

Protein

Protein identifiers

Inositol-trisphosphate 3-kinase A — P23677 (reviewed: P23677)

Alternative names: Inositol 1,4,5-trisphosphate 3-kinase A

All UniProt accessions (2): C9JC74, P23677

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of 1D-myo-inositol 1,4,5-trisphosphate (InsP3) into 1D-myo-inositol 1,3,4,5-tetrakisphosphate and participates to the regulation of calcium homeostasis.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Expressed in brain.

Activity regulation. Activated by calcium/calmodulin.

Similarity. Belongs to the inositol phosphokinase (IPK) family.

RefSeq proteins (1): NP_002211* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005522	IPK	Family
IPR038286	IPK_sf	Homologous_superfamily

Pfam: PF03770

Enzyme classification (BRENDA):

• EC 2.7.1.127 — inositol-trisphosphate 3-kinase (BRENDA: 14 organisms, 87 substrates, 104 inhibitors, 42 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE	0.0002–0.011	21
ATP	0.033–2.5	13
1D-MYO-INOSITOL 2,4,5-TRISPHOSPHATE	0.0015–0.005	2
INSP3	0.0002–0.0017	2

Catalyzed reactions (Rhea), 1 shown:

• 1D-myo-inositol 1,4,5-trisphosphate + ATP = 1D-myo-inositol 1,3,4,5-tetrakisphosphate + ADP + H(+) (RHEA:11020)

UniProt features (56 total): helix 13, strand 13, binding site 10, mutagenesis site 6, modified residue 5, region of interest 4, turn 2, chain 1, sequence conflict 1, compositionally biased region 1

Structure

Experimental structures (PDB)

17 structures.

PDB	Method	Resolution (Å)
8PP8	X-RAY DIFFRACTION	1.59
8PPE	X-RAY DIFFRACTION	1.59
8PPI	X-RAY DIFFRACTION	1.65
8PPH	X-RAY DIFFRACTION	1.7
8PP9	X-RAY DIFFRACTION	1.73
8PPA	X-RAY DIFFRACTION	1.73
8PPG	X-RAY DIFFRACTION	1.75
8PPJ	X-RAY DIFFRACTION	1.75
8PPD	X-RAY DIFFRACTION	1.77
1W2F	X-RAY DIFFRACTION	1.8
8PPB	X-RAY DIFFRACTION	1.8
8PPF	X-RAY DIFFRACTION	1.85
8PPC	X-RAY DIFFRACTION	1.92
1W2D	X-RAY DIFFRACTION	1.94
1W2C	X-RAY DIFFRACTION	1.95
4UPU	X-RAY DIFFRACTION	2.34
9QGK	ELECTRON MICROSCOPY	2.97

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23677-F1	72.70	0.54

Functional residue map

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

Ligand- & substrate-binding residues (10): 264; 285; 312–319; 336; 416; 419; 197; 209; 249–251; 262

Post-translational modifications (5): 35, 55, 62, 137, 197

Mutagenesis-validated functional residues (6):

Position	Phenotype
188	decreases to 44% of kinase activity.
199	decreases to 80% of kinase activity.
262	decreases to 12% of kinase activity.
264	loss of kinase activity.
319	loss of kinase activity.
416	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855204	Synthesis of IP3 and IP4 in the cytosol
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 199 (showing top): BROWNE_HCMV_INFECTION_30MIN_DN, GOBP_DENDRITE_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, SP3_Q3, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_DENDRITE_MORPHOGENESIS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_DENDRITIC_SPINE_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GOBP_CELLULAR_COMPONENT_MAINTENANCE, GOBP_NEUROGENESIS

GO Biological Process (11): inositol metabolic process (GO:0006020), signal transduction (GO:0007165), actin cytoskeleton organization (GO:0030036), inositol phosphate biosynthetic process (GO:0032958), phosphatidylinositol phosphate biosynthetic process (GO:0046854), regulation of synaptic plasticity (GO:0048167), response to calcium ion (GO:0051592), positive regulation of dendritic spine morphogenesis (GO:0061003), cellular response to calcium ion (GO:0071277), dendritic spine maintenance (GO:0097062), modification of postsynaptic actin cytoskeleton (GO:0098885)

GO Molecular Function (10): inositol hexakisphosphate kinase activity (GO:0000828), calcium/calmodulin-dependent protein kinase activity (GO:0004683), calmodulin binding (GO:0005516), ATP binding (GO:0005524), inositol-1,4,5-trisphosphate 3-kinase activity (GO:0008440), small GTPase binding (GO:0031267), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), inositol phosphate kinase activity (GO:0180030)

GO Cellular Component (7): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoskeleton (GO:0005856), dendritic spine (GO:0043197), postsynaptic actin cytoskeleton (GO:0098871), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Inositol phosphate metabolism	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
postsynapse	2
polyol metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytoskeleton organization	1
actin filament-based process	1
inositol phosphate metabolic process	1
polyol biosynthetic process	1
organophosphate biosynthetic process	1
glycerophospholipid biosynthetic process	1
modulation of chemical synaptic transmission	1
regulation of biological quality	1
response to metal ion	1
positive regulation of neuron projection development	1
positive regulation of dendrite morphogenesis	1
dendritic spine morphogenesis	1
positive regulation of dendritic spine development	1
regulation of dendritic spine morphogenesis	1
response to calcium ion	1
cellular response to metal ion	1
cellular component maintenance	1
dendritic spine organization	1
modification of postsynaptic structure	1
phosphotransferase activity, phosphate group as acceptor	1
inositol phosphate kinase activity	1
protein serine/threonine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
inositol trisphosphate kinase activity	1
GTPase binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
kinase activity	1

Protein interactions and networks

STRING

798 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ITPKA	IP6K3	Q96PC2	745
ITPKA	IP6K1	Q92551	739
ITPKA	IP6K2	Q9UHH9	651
ITPKA	IPMK	Q8NFU5	541
ITPKA	INPP5A	Q14642	519
ITPKA	CAMK2A	Q9UQM7	499
ITPKA	SV2B	Q7L1I2	456
ITPKA	UTRN	P46939	444
ITPKA	SLC17A7	Q9P2U7	440
ITPKA	CALM1	P02593	437
ITPKA	PLCB2	Q00722	433
ITPKA	GAD1	Q99259	427
ITPKA	IPPK	Q9H8X2	426
ITPKA	SLC8A2	Q9UPR5	425
ITPKA	BSX	Q3C1V8	425

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ERBB2	ITPKA	psi-mi:“MI:0915”(physical association)	0.370
DBN1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CALM1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350

BioGRID (16): ITPKA (Affinity Capture-MS), ITPKA (Two-hybrid), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Affinity Capture-MS), ITPKA (Affinity Capture-MS), ITPKA (Affinity Capture-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS), ITPKA (Proximity Label-MS)

ESM2 similar proteins: A3KN95, A4IFG4, A7E2I7, E2RDP2, J3QMI4, O94810, O95382, P0C5W1, P23677, P82350, Q15628, Q16586, Q1RMX3, Q24JP5, Q28686, Q29RH2, Q3T904, Q3U0S6, Q45T69, Q49LS1, Q5FWU3, Q5RCS0, Q5U651, Q64255, Q674R7, Q684M2, Q68FE2, Q68FE7, Q6EBV9, Q6GQT5, Q6NY19, Q6P9Q4, Q6PEY1, Q7Z3C6, Q80WF4, Q80XF7, Q86TL0, Q86XJ0, Q8C052, Q8C152

Diamond homologs: P17105, P23677, P27987, P42335, Q7TS72, Q80ZG2, Q8R071, Q95Q62, Q96DU7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
CAMK2A	up-regulates	ITPKA	phosphorylation
PRKCA	“down-regulates activity”	ITPKA
PRKACA	“up-regulates activity”	ITPKA	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	59
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

970 predictions. Top by Δscore:

Variant	Effect	Δscore
15:41494393:G:GT	donor_gain	1.0000
15:41494405:G:GT	donor_gain	1.0000
15:41494414:CAGG:C	donor_loss	1.0000
15:41494416:GG:G	donor_loss	1.0000
15:41494417:GT:G	donor_loss	1.0000
15:41501457:TTTCA:T	acceptor_loss	1.0000
15:41501458:TTCA:T	acceptor_loss	1.0000
15:41501459:TCA:T	acceptor_loss	1.0000
15:41501460:CAGAA:C	acceptor_loss	1.0000
15:41501461:A:AG	acceptor_gain	1.0000
15:41501461:AG:A	acceptor_loss	1.0000
15:41501462:G:GA	acceptor_gain	1.0000
15:41501462:GA:G	acceptor_gain	1.0000
15:41501462:GAA:G	acceptor_gain	1.0000
15:41501462:GAAA:G	acceptor_gain	1.0000
15:41501462:GAAAA:G	acceptor_gain	1.0000
15:41501634:GGGA:G	acceptor_gain	1.0000
15:41501851:GGTAT:G	donor_loss	1.0000
15:41501853:T:A	donor_loss	1.0000
15:41501986:C:CA	acceptor_gain	1.0000
15:41501992:CACA:C	acceptor_loss	1.0000
15:41501993:ACAG:A	acceptor_gain	1.0000
15:41501994:CA:C	acceptor_loss	1.0000
15:41501995:A:AG	acceptor_gain	1.0000
15:41501995:AG:A	acceptor_gain	1.0000
15:41501996:G:GA	acceptor_gain	1.0000
15:41501996:GG:G	acceptor_gain	1.0000
15:41501996:GGA:G	acceptor_gain	1.0000
15:41501996:GGAC:G	acceptor_gain	1.0000
15:41501996:GGACT:G	acceptor_gain	1.0000

AlphaMissense

2968 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:41501535:T:A	W188R	1.000
15:41501535:T:C	W188R	1.000
15:41501551:G:A	G193E	1.000
15:41501553:C:G	H194D	1.000
15:41501555:C:A	H194Q	1.000
15:41501555:C:G	H194Q	1.000
15:41501671:T:C	L208P	1.000
15:41501675:G:C	K209N	1.000
15:41501675:G:T	K209N	1.000
15:41501791:T:C	L248P	1.000
15:41501833:A:T	D262V	1.000
15:41501834:C:A	D262E	1.000
15:41501834:C:G	D262E	1.000
15:41501838:A:G	K264E	1.000
15:41501839:A:T	K264I	1.000
15:41501840:A:C	K264N	1.000
15:41501840:A:T	K264N	1.000
15:41501844:G:C	G266R	1.000
15:41501851:G:C	R268T	1.000
15:41501851:G:T	R268M	1.000
15:41501997:G:C	R268S	1.000
15:41501997:G:T	R268S	1.000
15:41502058:T:G	Y289D	1.000
15:41502068:T:C	M292T	1.000
15:41502068:T:G	M292R	1.000
15:41502122:T:A	V310D	1.000
15:41502127:A:G	K312E	1.000
15:41502129:G:C	K312N	1.000
15:41502129:G:T	K312N	1.000
15:41502136:T:C	Y315H	1.000

dbSNP variants (sampled 300 via entrez): RS1000100232 (15:41493215 G>A,C,T), RS1000264681 (15:41492106 G>A), RS1000837280 (15:41493686 G>A), RS1001057275 (15:41499689 CTG>C), RS1001238390 (15:41499860 C>T), RS1001374657 (15:41493922 T>C), RS1001625209 (15:41500961 A>G), RS1001770908 (15:41495079 C>T), RS1001948054 (15:41502876 C>G,T), RS1002103407 (15:41496243 A>G), RS1002157024 (15:41496012 G>A), RS1002607643 (15:41500026 T>G), RS1002890930 (15:41502266 C>A,G,T), RS1003183983 (15:41495822 G>C), RS1003249127 (15:41502529 G>C)

Disease associations

OMIM: gene MIM:147521 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST001728_13	Ulcerative colitis	2.000000e-08
GCST004613_44	Sum neutrophil eosinophil counts	2.000000e-10
GCST004620_92	Sum basophil neutrophil counts	4.000000e-11
GCST004623_70	Neutrophil percentage of granulocytes	3.000000e-12
GCST004629_139	Neutrophil count	2.000000e-11
GCST004632_43	Lymphocyte percentage of white cells	2.000000e-13
GCST004633_33	Neutrophil percentage of white cells	4.000000e-13
GCST005038_89	Allergic disease (asthma, hay fever or eczema)	5.000000e-10
GCST005196_7	Coronary artery disease	2.000000e-07
GCST006409_2	Allergic rhinitis	1.000000e-14
GCST007797_44	Asthma onset (childhood vs adult)	1.000000e-06
GCST007798_149	Asthma	8.000000e-12
GCST007800_67	Asthma (childhood onset)	2.000000e-18
GCST007930_7	Medication use (agents acting on the renin-angiotensin system)	2.000000e-10
GCST009720_60	Asthma	1.000000e-09
GCST010042_14	Asthma	1.000000e-11
GCST90002381_614	Eosinophil count	1.000000e-10
GCST90002382_235	Eosinophil percentage of white cells	2.000000e-17
GCST90002398_280	Neutrophil count	8.000000e-14
GCST90002399_361	Neutrophil percentage of white cells	3.000000e-18

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0005090	basophil count
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0004847	age at onset
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5164 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Inositol 1,4,5-trisphosphate 3-kinases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
GNF362	Inhibition	7.7	pIC50

Binding affinities (BindingDB)

1 measured of 24 human assays (24 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Purine, 10	IC50	150000 nM

PubChem BioAssay actives

1 with measured affinity, of 27 total; 1 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-N-[(4-nitrophenyl)methyl]-2-N-[[3-(trifluoromethyl)phenyl]methyl]-7H-purine-2,6-diamine	1799607: Inhibition Assay from Article 10.1002/1439-7633(20020902)3:9: “Purine-based inhibitors of inositol-1,4,5-trisphosphate-3-kinase.”	ki	4.3000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Tetrachlorodibenzodioxin	affects reaction, increases activity, affects expression, decreases expression	4
Cyclosporine	increases expression	3
Phenobarbital	affects expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
sodium arsenate	increases abundance, increases expression	1
beta-lapachone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	increases expression	1
benzo(e)pyrene	increases methylation	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Microplastics	increases abundance, increases expression	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases expression	1
Boron Compounds	increases expression	1
Caffeine	affects phosphorylation	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Diazinon	increases methylation	1
Methapyrilene	increases methylation	1
Polyethylene Terephthalates	increases abundance, increases expression	1
Quercetin	decreases expression	1

ChEMBL screening assays

3 unique, capped per target: 3 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5166057	Binding	Inhibition of N-terminal 6His-tagged/TEV cleavage site fused recombinant human IP3KA (173 to 461 residues) expressed in Escherichia coli using [3H]-Ins91,4,5)P3 as substrate measured after 60 mins by HPLC analysis	Development of Novel IP6K Inhibitors for the Treatment of Obesity and Obesity-Induced Metabolic Dysfunctions. — J Med Chem

Clinical trials (associated diseases)

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