IP6K3

Summary

IP6K3 (inositol hexakisphosphate kinase 3, HGNC:17269) is a protein-coding gene on chromosome 6p21.31, encoding Inositol hexakisphosphate kinase 3 (Q96PC2). Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).

This gene encodes a protein that belongs to the inositol phosphokinase (IPK) family. This protein is likely responsible for the conversion of inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). It may also convert 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4. Alternative splicing results in multiple transcript variants encoding the same protein.

Source: NCBI Gene 117283 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 82 total
• Druggable target: yes
• MANE Select transcript: NM_054111

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17269
Approved symbol	IP6K3
Name	inositol hexakisphosphate kinase 3
Location	6p21.31
Locus type	gene with protein product
Status	Approved
Aliases	INSP6K3
Ensembl gene	ENSG00000161896
Ensembl biotype	protein_coding
OMIM	606993
Entrez	117283

Gene structure

Transcript identifiers

Ensembl transcripts: 22 — 22 protein_coding

ENST00000293756, ENST00000451316, ENST00000634274, ENST00000885829, ENST00000885830, ENST00000885831, ENST00000885832, ENST00000885833, ENST00000885834, ENST00000959466, ENST00000959467, ENST00000959468, ENST00000959469, ENST00000959470, ENST00000959471, ENST00000959472, ENST00000959473, ENST00000959474, ENST00000959475, ENST00000959476, ENST00000959477, ENST00000959478

RefSeq mRNA: 2 — MANE Select: NM_054111 NM_001142883, NM_054111

CCDS: CCDS34435

Canonical transcript exons

ENST00000293756 — 6 exons

Exon	Start	End
ENSE00001061198	33725441	33725616
ENSE00001061200	33735278	33735655
ENSE00001061219	33726731	33726906
ENSE00001373156	33728087	33728300
ENSE00001810950	33721662	33723187
ENSE00001877843	33746758	33746905

Expression profiles

Bgee: expression breadth ubiquitous, 193 present calls, max score 98.36.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9594 / max 229.4400, expressed in 468 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
73180	2.3544	398
73183	0.3423	181
73182	0.1784	82
73181	0.0843	41

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
gastrocnemius	UBERON:0001388	98.36	gold quality
tibialis anterior	UBERON:0001385	98.34	gold quality
muscle of leg	UBERON:0001383	96.13	gold quality
hindlimb stylopod muscle	UBERON:0004252	96.13	gold quality
muscle organ	UBERON:0001630	95.89	gold quality
skeletal muscle organ	UBERON:0014892	95.89	gold quality
deltoid	UBERON:0001476	95.73	gold quality
skeletal muscle tissue	UBERON:0001134	95.48	gold quality
quadriceps femoris	UBERON:0001377	95.21	gold quality
vastus lateralis	UBERON:0001379	94.81	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.20	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.92	gold quality
biceps brachii	UBERON:0001507	91.79	gold quality
muscle tissue	UBERON:0002385	91.41	gold quality
apex of heart	UBERON:0002098	89.88	gold quality
heart left ventricle	UBERON:0002084	88.87	gold quality
cardiac ventricle	UBERON:0002082	88.65	gold quality
left ventricle myocardium	UBERON:0006566	87.26	silver quality
endothelial cell	CL:0000115	86.86	gold quality
kidney epithelium	UBERON:0004819	85.61	silver quality
heart right ventricle	UBERON:0002080	85.02	gold quality
heart	UBERON:0000948	82.82	gold quality
myocardium	UBERON:0002349	82.82	silver quality
buccal mucosa cell	CL:0002336	82.64	gold quality
right atrium auricular region	UBERON:0006631	82.44	gold quality
medial globus pallidus	UBERON:0002477	82.29	gold quality
cardiac atrium	UBERON:0002081	82.16	gold quality
body of tongue	UBERON:0011876	80.96	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	80.81	gold quality
globus pallidus	UBERON:0001875	80.14	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR3C1

miRNA regulators (miRDB)

52 targeting IP6K3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-10393-3P	99.72	66.56	961
HSA-MIR-6801-5P	99.72	66.50	981
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-298	99.63	67.56	1916
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-217-5P	99.49	69.93	1419
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-508-5P	99.41	64.25	1248
HSA-MIR-6739-3P	99.22	68.84	1843
HSA-MIR-4291	99.20	68.88	2969
HSA-MIR-661	99.09	65.94	2062

Literature-anchored findings (GeneRIF, showing 3)

• Two SNPs in the 5’-flanking promoter region of the IP6K3 gene were found to be associated with sporadic late onset Alzheimer’s disease. Characterizing the functionality of the two polymorphisms by luciferase assay revealed that one of them (rs28607030) affects IP6K3 promoter activity, with the G allele showing an increased activity. (PMID:27345265)
• High levels of IP6K3 mRNA were found in myotubes and muscle tissues. In myotubes, IP6K3 was upregulated by dexamethasone treatment, which is known to inhibit glucose metabolism. (PMID:27577108)
• IP6K3 and IPMK variations in LOAD and longevity: Evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival. (PMID:33497757)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ip6k3	ENSMUSG00000024210
rattus_norvegicus	Ip6k3	ENSRNOG00000025883
drosophila_melanogaster	IP3K1	FBGN0032147
drosophila_melanogaster	Ip6k	FBGN0034644
caenorhabditis_elegans	lfe-2	WBGENE00002979
caenorhabditis_elegans	F30A10.3	WBGENE00009262

Paralogs (6): IP6K2 (ENSG00000068745), ITPKC (ENSG00000086544), ITPKA (ENSG00000137825), ITPKB (ENSG00000143772), IPMK (ENSG00000151151), IP6K1 (ENSG00000176095)

Protein

Protein identifiers

Inositol hexakisphosphate kinase 3 — Q96PC2 (reviewed: Q96PC2)

Alternative names: Inositol hexaphosphate kinase 3

All UniProt accessions (3): A0A0U1RRE0, Q96PC2, Q5TAQ4

UniProt curated annotations — full annotation on UniProt →

Function. Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5). Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.

Subcellular location. Cytoplasm.

Tissue specificity. Detected in brain.

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

RefSeq proteins (2): NP_001136355, NP_473452* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005522	IPK	Family
IPR038286	IPK_sf	Homologous_superfamily

Pfam: PF03770

Enzyme classification (BRENDA):

• EC 2.7.4.21 — inositol-hexakisphosphate 5-kinase (BRENDA: 10 organisms, 35 substrates, 31 inhibitors, 11 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
ATP	0.037–1.4	4
INOSITOL HEXAKISPHOSPHATE	0.0007–0.0061	3
1D-MYO-INOSITOL HEXAKISPHOSPHATE	0.0004	1
5-DIPHOSPHO-1D-MYO-INOSITOL (1,2,3,4,6)PENTAKISP	0.002	1
ADP	1.57	1
D-MYO-INOSITOL-1,3,4,5,6-PENTAKISPHOSPHATE	0.0055	1

Catalyzed reactions (Rhea), 2 shown:

• 1D-myo-inositol hexakisphosphate + ATP = 5-diphospho-1D-myo-inositol 1,2,3,4,6-pentakisphosphate + ADP (RHEA:12793)
• 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate + ATP + H(+) = 1,5-bis(diphospho)-1D-myo-inositol 2,3,4,6-tetrakisphosphate + ADP (RHEA:37467)

UniProt features (11 total): sequence variant 4, sequence conflict 2, mutagenesis site 2, chain 1, region of interest 1, binding site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96PC2-F1	76.40	0.55

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 (1): 211–219

Mutagenesis-validated functional residues (2):

Position	Phenotype
217	loss of activity.
325	strongly reduces activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855167	Synthesis of pyrophosphates in the cytosol
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 77 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, TGIF_01, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (7): protein phosphorylation (GO:0006468), inositol phosphate biosynthetic process (GO:0032958), locomotion (GO:0040011), inositol phosphate metabolic process (GO:0043647), phosphatidylinositol metabolic process (GO:0046488), phosphatidylinositol phosphate biosynthetic process (GO:0046854), organophosphate biosynthetic process (GO:0090407)

GO Molecular Function (12): inositol-1,3,4,5,6-pentakisphosphate kinase activity (GO:0000827), inositol hexakisphosphate kinase activity (GO:0000828), diphosphoinositol pentakisphosphate kinase activity (GO:0000829), inositol hexakisphosphate 6-kinase activity (GO:0000831), inositol hexakisphosphate 5-kinase activity (GO:0000832), ATP binding (GO:0005524), inositol 5-diphosphate pentakisphosphate 5-kinase activity (GO:0052836), diphosphoinositol tetrakisphosphate kinase activity (GO:0052839), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytosol (GO:0005829)

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
inositol phosphate kinase activity	5
phosphotransferase activity, phosphate group as acceptor	3
organophosphate metabolic process	2
inositol hexakisphosphate kinase activity	2
phosphotransferase activity, alcohol group as acceptor	2
cellular anatomical structure	2
phosphorylation	1
protein modification process	1
inositol phosphate metabolic process	1
polyol biosynthetic process	1
organophosphate biosynthetic process	1
biological_process	1
polyol metabolic process	1
phosphorus metabolic process	1
glycerophospholipid biosynthetic process	1
biosynthetic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

736 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IP6K3	PPIP5K1	Q6PFW1	955
IP6K3	PPIP5K2	O43314	914
IP6K3	ITPKB	P27987	761
IP6K3	ITPKA	P23677	745
IP6K3	ADD2	P35612	588
IP6K3	ADD3	Q9UEY8	581
IP6K3	ADD1	P35611	576
IP6K3	IPPK	Q9H8X2	574
IP6K3	CA4	P22748	513
IP6K3	MINPP1	Q9UNW1	498
IP6K3	GALNT18	Q6P9A2	456
IP6K3	POLR1F	Q3B726	452
IP6K3	INPP1	P49441	433
IP6K3	A0A2R8Y809	A0A2R8Y809	399
IP6K3	TBCE	Q15813	399

IntAct

53 interactions, top by confidence:

A	B	Type	Score
TRIP6	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
TRIM27	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
TRAF3	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
IP6K3	ZRANB1	psi-mi:“MI:0915”(physical association)	0.560
MEOX2	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
NOTO	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
IP6K3	NIF3L1	psi-mi:“MI:0915”(physical association)	0.560
IP6K3	MED4	psi-mi:“MI:0915”(physical association)	0.560
POLR2E	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
FHL5	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
LNX1	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
ZNF655	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	IP6K3	psi-mi:“MI:0915”(physical association)	0.560
Smad3		psi-mi:“MI:0914”(association)	0.350
MAPK3		psi-mi:“MI:0914”(association)	0.350
IP6K3	MAP3K3	psi-mi:“MI:0914”(association)	0.350
IP6K3	PROZ	psi-mi:“MI:0914”(association)	0.350
IP6K3	TRIP6	psi-mi:“MI:0915”(physical association)	0.000
IP6K3	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.000
IP6K3	TRAF2	psi-mi:“MI:0915”(physical association)	0.000
IP6K3	TRIM27	psi-mi:“MI:0915”(physical association)	0.000
TRAF3	IP6K3	psi-mi:“MI:0915”(physical association)	0.000
IP6K3	ZRANB1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (37): MAP3K3 (Affinity Capture-MS), PCCA (Affinity Capture-MS), BAG6 (Affinity Capture-MS), UBL4A (Affinity Capture-MS), TARDBP (Affinity Capture-MS), PHF21A (Affinity Capture-MS), SRRT (Affinity Capture-MS), ELP3 (Affinity Capture-MS), BAIAP2L1 (Affinity Capture-MS), NUP107 (Affinity Capture-MS), IP6K3 (Affinity Capture-MS), IP6K3 (Affinity Capture-MS), PCYT1A (Affinity Capture-MS), NECAB1 (Affinity Capture-MS), PROZ (Affinity Capture-MS)

ESM2 similar proteins: A2A2Y4, E1C3P4, F1N2W9, F1QDI9, O88370, O95453, P0C0T1, P50747, P55266, P69341, Q13572, Q2KHI9, Q2TBA3, Q496Y0, Q5F480, Q5R488, Q5R803, Q5RC51, Q69ZK0, Q6GR37, Q7SY78, Q7TT16, Q80V72, Q8BHD4, Q8BWD2, Q8BYN3, Q8HXH0, Q8K1Y2, Q8K214, Q8K2I9, Q8NFU5, Q8NFZ0, Q8TCU6, Q8VDG3, Q91XU3, Q920N2, Q92551, Q95221, Q96EN8, Q96PC2

Diamond homologs: O74561, Q12494, Q6PD10, Q80V72, Q8BWD2, Q92551, Q95221, Q96PC2, Q9ESM0, Q9R0U1, Q9UHH9, A2X5H5, Q6H545, Q7TT16, Q8NFU5, Q99NI4, Q9US14, Q9FLT2, Q9LY23

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	73
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1514 predictions. Top by Δscore:

Variant	Effect	Δscore
6:33725564:C:CT	acceptor_gain	1.0000
6:33725564:C:T	acceptor_gain	1.0000
6:33726815:T:TA	donor_gain	1.0000
6:33735273:CTCA:C	donor_loss	1.0000
6:33735274:TCA:T	donor_loss	1.0000
6:33735275:CA:C	donor_loss	1.0000
6:33735276:A:AT	donor_loss	1.0000
6:33735652:TCCT:T	acceptor_gain	1.0000
6:33735653:CCTC:C	acceptor_gain	1.0000
6:33735654:CT:C	acceptor_gain	1.0000
6:33735656:C:CC	acceptor_gain	1.0000
6:33735657:T:A	acceptor_loss	1.0000
6:33735665:A:T	acceptor_gain	1.0000
6:33746752:ACTC:A	donor_loss	1.0000
6:33746753:CTCA:C	donor_loss	1.0000
6:33746754:TCA:T	donor_loss	1.0000
6:33746755:CACCA:C	donor_loss	1.0000
6:33746756:A:AC	donor_gain	1.0000
6:33746756:ACCA:A	donor_loss	1.0000
6:33746757:C:CC	donor_gain	1.0000
6:33725436:CCTA:C	donor_loss	0.9900
6:33725437:CTACC:C	donor_loss	0.9900
6:33725438:TACC:T	donor_loss	0.9900
6:33725439:A:C	donor_loss	0.9900
6:33725440:C:CG	donor_loss	0.9900
6:33725565:A:T	acceptor_gain	0.9900
6:33725593:C:CC	acceptor_gain	0.9900
6:33726729:A:AC	donor_gain	0.9900
6:33726730:C:CC	donor_gain	0.9900
6:33726734:G:A	donor_gain	0.9900

AlphaMissense

2700 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:33725559:A:G	L216P	0.999
6:33725555:C:A	K217N	0.998
6:33725555:C:G	K217N	0.998
6:33735354:C:A	K41N	0.998
6:33735354:C:G	K41N	0.998
6:33722757:A:G	L399P	0.997
6:33722981:G:C	S324R	0.997
6:33722981:G:T	S324R	0.997
6:33722983:T:G	S324R	0.997
6:33723092:G:C	F287L	0.997
6:33723092:G:T	F287L	0.997
6:33723094:A:G	F287L	0.997
6:33723146:C:A	K269N	0.997
6:33723146:C:G	K269N	0.997
6:33725562:T:G	D215A	0.997
6:33725565:A:G	L214P	0.997
6:33722846:G:C	D369E	0.996
6:33722846:G:T	D369E	0.996
6:33725562:T:C	D215G	0.996
6:33722856:C:G	R366P	0.995
6:33722976:A:G	L326P	0.995
6:33725480:G:C	S242R	0.995
6:33725480:G:T	S242R	0.995
6:33725482:T:G	S242R	0.995
6:33725561:A:C	D215E	0.995
6:33725561:A:T	D215E	0.995
6:33725562:T:A	D215V	0.995
6:33725568:A:T	V213D	0.995
6:33725570:A:C	C212W	0.995
6:33735294:G:C	F61L	0.995

dbSNP variants (sampled 300 via entrez): RS1000092290 (6:33727765 T>G), RS1000123645 (6:33733596 A>C), RS1000159912 (6:33745577 G>A), RS1000161612 (6:33744852 C>T), RS1000218044 (6:33736004 C>T), RS1000363726 (6:33747997 G>A), RS1000396627 (6:33748214 C>G,T), RS1000494298 (6:33730583 G>A), RS1000859455 (6:33726519 A>G,T), RS1001097035 (6:33731770 A>G), RS1001554382 (6:33741115 C>G,T), RS1001585384 (6:33741409 A>G), RS1001679361 (6:33761319 T>C), RS1001697654 (6:33753237 G>A), RS1001780768 (6:33760992 T>C)

Disease associations

OMIM: gene MIM:606993 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST002094_5	Crohn’s disease	1.000000e-08
GCST004607_139	Plateletcrit	3.000000e-67
GCST005951_153	Body mass index	5.000000e-09
GCST005981_8	Phosphorus levels	2.000000e-13
GCST006920_1	Regular attendance at a gym or sports club	4.000000e-08
GCST007062_2	Hodgkin’s lymphoma	2.000000e-10
GCST007127_1	Multiple sclerosis and waist-to-hip-ratio (pleiotropy)	5.000000e-06
GCST007656_5	Chronic obstructive pulmonary disease or resting heart rate (pleiotropy)	3.000000e-15
GCST008163_73	Height	6.000000e-06
GCST008595_173	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	2.000000e-12
GCST008919_7	Asthma and attention deficit hyperactivity disorder	4.000000e-08
GCST010242_160	HDL cholesterol levels	9.000000e-12
GCST90000025_488	Appendicular lean mass	1.000000e-16
GCST90002400_574	Plateletcrit	5.000000e-19
GCST90002402_688	Platelet count	4.000000e-18

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit
EFO:0004340	body mass index
EFO:0004861	phosphorus measurement
EFO:0009592	social interaction measurement
EFO:0004343	waist-hip ratio
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0004980	appendicular lean mass
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523431 (SINGLE PROTEIN)

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

ChEMBL bioactivities

37 potent at pChembl≥5 of 50 total, top 37 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.10	IC50	8	nM	CHEMBL5203174
6.70	IC50	200	nM	CHEMBL5181623
6.70	IC50	200	nM	CHEMBL5171388
6.68	IC50	210	nM	CHEMBL5206215
6.62	IC50	240	nM	CHEMBL5190343
6.62	IC50	240	nM	CHEMBL5197626
6.47	IC50	340	nM	CHEMBL5198845
6.37	IC50	430	nM	CHEMBL5185229
6.26	IC50	550	nM	CHEMBL5185725
6.21	IC50	610	nM	CHEMBL5169462
6.17	IC50	670	nM	CHEMBL5201078
6.12	IC50	760	nM	CHEMBL5184960
6.08	IC50	840	nM	CHEMBL5184940
6.07	IC50	850	nM	CHEMBL5196483
5.89	IC50	1290	nM	CHEMBL5186210
5.88	IC50	1323	nM	CHEMBL5190343
5.85	IC50	1410	nM	CHEMBL5186729
5.78	IC50	1650	nM	CHEMBL5178548
5.75	IC50	1790	nM	CHEMBL5175579
5.69	IC50	2060	nM	CHEMBL5195827
5.66	IC50	2170	nM	CHEMBL5188320
5.65	IC50	2250	nM	CHEMBL5192487
5.61	IC50	2440	nM	CHEMBL5204881
5.57	IC50	2690	nM	CHEMBL1460920
5.57	IC50	2680	nM	CHEMBL5437046
5.55	IC50	2810	nM	CHEMBL5189856
5.51	IC50	3080	nM	CHEMBL1485263
5.51	IC50	3090	nM	CHEMBL5200214
5.45	IC50	3590	nM	CHEMBL5190846
5.43	IC50	3720	nM	CHEMBL1368139
5.33	IC50	4620	nM	CHEMBL5205377
5.17	IC50	6830	nM	CHEMBL5209246
5.11	IC50	7810	nM	CHEMBL1379963
5.08	IC50	8370	nM	CHEMBL5201056
5.04	IC50	9210	nM	CHEMBL5398968
5.02	Ki	9620	nM	CHEMBL4555782
5.00	IC50	1.01e+04	nM	CHEMBL5398912

PubChem BioAssay actives

36 with measured affinity, of 52 total; 35 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
1’-(4-chlorobenzoyl)-2-oxospiro[1H-indole-3,4’-piperidine]-5-carboxylic acid	1909474: Inhibition of recombinant full length human IP6K3 assessed as inorganic phosphate release measured after 2 hrs by ADP-Glo Max assay	ic50	0.0080	uM
3-(4-benzamidophenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.2000	uM
(E)-3-[3-(4-phenylphenyl)-2,1-benzoxazol-5-yl]prop-2-enoic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.2000	uM
3-[4-(2-methylpropanoylamino)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.2100	uM
3-(4-phenylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.2400	uM
3-[4-(cyclopentanecarbonylamino)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.2400	uM
3-[4-(propan-2-ylcarbamoyl)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.3400	uM
3-[4-(pyrimidine-4-carbonylamino)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.4300	uM
3-(4-phenoxyphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.5500	uM
3-(4-pyridin-3-ylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.6100	uM
3-(4-pyridin-4-ylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.6700	uM
(E)-3-[3-(4-phenoxyphenyl)-2,1-benzoxazol-5-yl]prop-2-enoic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.7600	uM
3-(3-phenylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.8400	uM
3-(3-phenoxyphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	0.8500	uM
3-(4-benzylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	1.2900	uM
3-(3-methylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	1.4100	uM
3-[4-[(6-oxopiperidine-3-carbonyl)amino]phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	1.6500	uM
3-(4-piperidin-1-ylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	1.7900	uM
3-(4-pyridin-2-yloxyphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	2.0600	uM
3-[4-(2-oxopyrrolidin-1-yl)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	2.1700	uM
3-[4-[(3,5-dichloro-2-pyridinyl)oxy]phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	2.2500	uM
3-(3,5-dimethylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	2.4400	uM
6-[(E)-2-(4-fluorophenyl)ethenyl]-3H-quinazolin-4-one	2038718: Inhibition of IP6K3 (unknown origin) incubated for 2 hrs in presence of ATP by ADPGlo reagent based assay	ic50	2.6800	uM
3-phenyl-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	2.6900	uM
3-[3-(cyclopropanecarbonylamino)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	2.8100	uM
(E)-3-(3-phenyl-2,1-benzoxazol-6-yl)prop-2-enoic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	3.0800	uM
3-[3-[(3,5-dichloro-2-pyridinyl)oxy]phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	3.0900	uM
(E)-3-[3-(3-methylphenyl)-2,1-benzoxazol-5-yl]prop-2-enoic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	3.5900	uM
(E)-3-(3-phenyl-2,1-benzoxazol-5-yl)prop-2-enoic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	3.7200	uM
3-[3-(trifluoromethyl)phenyl]-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	4.6200	uM
N-methyl-3-phenyl-2,1-benzoxazole-5-carboxamide	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	6.8300	uM
3-(4-methylphenyl)-2,1-benzoxazole-5-carboxylic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	7.8100	uM
(E)-3-[3-[4-(trifluoromethoxy)phenyl]-2,1-benzoxazol-5-yl]prop-2-enoic acid	1909470: Inhibition of N-terminal 6His-sumo-tagged recombinant human IP6K3 expressed in Escherichia coli assessed as inorganic phosphate release using InsP6 as substrate in presence of ATP measured after 60 to 120 mins by malachite green based colorimetric - DIPP1 coupled enzyme assay	ic50	8.3700	uM
6-[(4aR,8aS)-3,4,4a,5,6,7,8,8a-octahydro-1H-isoquinolin-2-yl]-3H-quinazolin-4-one	2038718: Inhibition of IP6K3 (unknown origin) incubated for 2 hrs in presence of ATP by ADPGlo reagent based assay	ic50	9.2100	uM
5-[[[2-[2-(6-methoxy-1H-indol-3-yl)ethylamino]-7H-purin-6-yl]amino]methyl]-1H-pyridin-2-one	1601028: Inhibition of IP6K3 (unknown origin) in presence of ATP at Km concentration by Cheng-Prusoff equation analysis	ki	9.6200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression, decreases expression	5
Benzo(a)pyrene	affects methylation, increases expression	4
Aflatoxin B1	affects expression, increases expression	4
Estradiol	affects cotreatment, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
aristolochic acid I	increases expression	1
4-biphenylamine	decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
trichostatin A	increases expression	1
bromoacetate	increases expression	1
cupric chloride	decreases expression	1
entinostat	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
SRT2183	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	increases expression	1
Cisplatin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Ethyl Methanesulfonate	increases expression	1
Phthalic Acids	increases methylation	1
Tetrachlorodibenzodioxin	decreases expression	1
Triclosan	increases expression	1
Urethane	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4400030	Binding	Inhibition of IP6K3 (unknown origin) in presence of ATP at Km concentration by Cheng-Prusoff equation analysis	Synthesis and characterization of novel isoform-selective IP6K1 inhibitors. — Bioorg Med Chem Lett

Clinical trials (associated diseases)

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