IPMK

Summary

IPMK (inositol polyphosphate multikinase, HGNC:20739) is a protein-coding gene on chromosome 10q21.1, encoding Inositol polyphosphate multikinase (Q8NFU5). Inositol phosphate kinase with a broad substrate specificity.

This gene encodes a member of the inositol phosphokinase family. The encoded protein has 3-kinase, 5-kinase and 6-kinase activities on phosphorylated inositol substrates. The encoded protein plays an important role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate, and has a preferred 5-kinase activity. This gene may play a role in nuclear mRNA export. Pseudogenes of this gene are located on the long arm of chromosome 13 and the short arm of chromosome 19.

Source: NCBI Gene 253430 — RefSeq curated summary.

At a glance

• Gene–disease (curated): hereditary neuroendocrine tumor of small intestine (Supportive, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 62 total
• Druggable target: yes — 3 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_152230

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20739
Approved symbol	IPMK
Name	inositol polyphosphate multikinase
Location	10q21.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000151151
Ensembl biotype	protein_coding
OMIM	609851
Entrez	253430

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000373935, ENST00000891909, ENST00000891910

RefSeq mRNA: 1 — MANE Select: NM_152230 NM_152230

CCDS: CCDS7250

Canonical transcript exons

ENST00000373935 — 6 exons

Exon	Start	End
ENSE00000997987	58237729	58237814
ENSE00001096229	58216145	58216317
ENSE00001096230	58227043	58227139
ENSE00001096232	58199240	58199321
ENSE00001461961	58191517	58196698
ENSE00001461963	58267422	58267894

Expression profiles

Bgee: expression breadth ubiquitous, 249 present calls, max score 91.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.9484 / max 758.6153, expressed in 1679 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
109433	9.1383	1665
109432	0.8101	364

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	91.70	gold quality
amniotic fluid	UBERON:0000173	88.74	gold quality
epithelial cell of pancreas	CL:0000083	87.24	gold quality
monocyte	CL:0000576	86.04	gold quality
leukocyte	CL:0000738	85.71	gold quality
upper arm skin	UBERON:0004263	84.89	silver quality
mucosa of paranasal sinus	UBERON:0005030	83.63	gold quality
right lobe of liver	UBERON:0001114	83.59	gold quality
gingival epithelium	UBERON:0001949	83.58	silver quality
epithelium of nasopharynx	UBERON:0001951	83.54	gold quality
cortical plate	UBERON:0005343	82.45	gold quality
nasal cavity epithelium	UBERON:0005384	81.79	silver quality
endothelial cell	CL:0000115	81.69	silver quality
gingiva	UBERON:0001828	81.69	gold quality
esophagus squamous epithelium	UBERON:0006920	81.48	gold quality
islet of Langerhans	UBERON:0000006	80.80	gold quality
ventricular zone	UBERON:0003053	80.71	gold quality
colonic mucosa	UBERON:0000317	80.61	gold quality
blood	UBERON:0000178	80.51	gold quality
oocyte	CL:0000023	80.24	gold quality
superficial temporal artery	UBERON:0001614	80.11	silver quality
ganglionic eminence	UBERON:0004023	79.74	gold quality
jejunal mucosa	UBERON:0000399	79.34	gold quality
Brodmann (1909) area 23	UBERON:0013554	79.18	gold quality
mucosa of sigmoid colon	UBERON:0004993	79.16	gold quality
oviduct epithelium	UBERON:0004804	79.08	gold quality
gall bladder	UBERON:0002110	78.99	gold quality
bronchial epithelial cell	CL:0002328	78.94	gold quality
middle temporal gyrus	UBERON:0002771	78.77	gold quality
oral cavity	UBERON:0000167	78.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.87

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

297 targeting IPMK, 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-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-186-5P	99.99	70.83	3707

Literature-anchored findings (GeneRIF, showing 20)

• cloning of a full-length 1248-bp cDNA encoding a human inositol phosphate multikinase (IPMK); localized predominantly in the nucleus when transiently expressed in mammalian cells (PMID:12027805)
• the major activity of human InsP(4) 5-kinase is phosphorylation at the D-5 position [InsP(4) 5-kinase] (PMID:12223481)
• Data show that inositol polyphosphate multikinase (IPMK) interacts with the nuclear receptor steroidogenic factor 1 (SF-1) and phosphorylates its bound ligand Phosphatidylinositol 4,5-bisphosphate (PIP). (PMID:22715467)
• Phosphorylation of S284 by protein kinase CK2 significantly decreases nuclear targeting of IPMK in HEK-293 cells. (PMID:22718630)
• overview of possible roles of IPMK in regulation of metabolism: IPMK appears to mediate activation of mammalian target of rapamycin (mTOR) in response to essential amino acids. IPMK appears to mediate hypothalamic control of food intake. [REVIEW] (PMID:23050966)
• Knockdown of expression and/or inhibition of function of phospholipase Cgamma1, inositol polyphosphate multikinase, which generates inositol 1,3,4,5-tetrakisphosphate (InsP) and InsP, and inositol hexakisphosphate kinase 1/2 (PMID:23322705)
• Results suggest that inositol polyphosphate multikinase (IPMK) acts as a transcriptional coactivator for p53 and that it is an integral part of the p53 transcriptional complex facilitating cell death. (PMID:23550211)
• Our findings implicate IPMK in a transcript-selective mRNA export pathway controlled by phosphoinositide turnover that preserves genome integrity in humans. (PMID:24074953)
• Future research should focus on the hitherto unknown non-conventional import of IPMK and the potential impact of its dysregulation on IPMK signaling pathways regulating cellular growth and proliferation. (PMID:24632208)
• A hereditary form of small intestinal carcinoid associated with a germline mutation in IPMK. (PMID:25865046)
• a severe loss of IPMK in the striatum of Huntington disease patients and in several cellular and animal models of the disease, is reported. (PMID:26195796)
• IPMK is a versatile regulator of nuclear signaling events. (Review) (PMID:26682649)
• This study demonstrated that identified genetic overlap between Alzheimer Disease disease and immune-mediated diseases, implicating the HLA locus and IPMK in the pathobiology of Alzheimer Disease. (PMID:27088644)
• No IPMK mutation was found in constitutional or tumor DNA in patients with familial small-intestine neuroendocrine carcinoids. CGH array revealed recurrent chromosome-18 deletions but no alteration in the IPMK region. (PMID:27825921)
• Data suggest that IPMK exhibits constrained, horseshoe-shaped substrate pocket, formed from an alpha-helix, a 3(10) helix, and a recently evolved tri-proline loop; headgroups of substrates (inositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate) bind in precisely the same orientation, indicative of evolutionary optimization of 3-kinase activities against both substrates. (PMID:28882892)
• rs2790234 and rs6481383 are associated with longevity in women. (PMID:30744060)
• Deletion of IPMK in cell lines and intact mice virtually abolishes lipophagy, promotes liver damage as well as inflammation, and impairs hepatocyte regeneration. (PMID:30840891)
• Inositol Polyphosphate Multikinase Inhibits Liquid-Liquid Phase Separation of TFEB to Negatively Regulate Autophagy Activity. (PMID:33290695)
• IP6K3 and IPMK variations in LOAD and longevity: Evidence for a multifaceted signaling network at the crossroad between neurodegeneration and survival. (PMID:33497757)
• miRNA-Induced Downregulation of IPMK in Macrophages Mediates Lipopolysaccharide-Triggered TLR4 Signaling. (PMID:36830701)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	ipmkb	ENSDARG00000029291
danio_rerio	ipmka	ENSDARG00000076699
mus_musculus	Ipmk	ENSMUSG00000060733
rattus_norvegicus	Ipmk	ENSRNOG00000000609
drosophila_melanogaster	Ipk2	FBGN0031267
caenorhabditis_elegans		WBGENE00014081

Paralogs (6): IP6K2 (ENSG00000068745), ITPKC (ENSG00000086544), ITPKA (ENSG00000137825), ITPKB (ENSG00000143772), IP6K3 (ENSG00000161896), IP6K1 (ENSG00000176095)

Protein

Protein identifiers

Inositol polyphosphate multikinase — Q8NFU5 (reviewed: Q8NFU5)

Alternative names: Inositol 1,3,4,6-tetrakisphosphate 5-kinase

All UniProt accessions (1): Q8NFU5

UniProt curated annotations — full annotation on UniProt →

Function. Inositol phosphate kinase with a broad substrate specificity. Phosphorylates inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) first to inositol 1,3,4,5-tetrakisphosphate and then to inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5). Phosphorylates inositol 1,3,4,6-tetrakisphosphate (Ins(1,3,4,6)P4). Phosphorylates inositol 1,4,5,6-tetrakisphosphate (Ins(1,4,5,6)P4). Phosphorylates glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate to glycero-3-phospho-1D-myo-inositol 3,4,5-trisphosphate. Plays an important role in MLKL-mediated necroptosis via its role in the biosynthesis of inositol pentakisphosphate (InsP5) and inositol hexakisphosphate (InsP6). Binding of these highly phosphorylated inositol phosphates to MLKL mediates the release of an N-terminal auto-inhibitory region, leading to activation of the kinase. Essential for activated phospho-MLKL to oligomerize and localize to the cell membrane during necroptosis. Required for normal embryonic development, probably via its role in the biosynthesis of inositol 1,3,4,5,6-pentakisphosphate (Ins(1,3,4,5,6)P5) and inositol hexakisphosphate (InsP6).

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous, with the highest expression in skeletal muscle, liver, placenta, lung, peripheral blood leukocytes, kidney, spleen and colon.

Activity regulation. Inhibited by flavonoids that occupy the ATP-binding pocket. Inhibited by myricetin, quercetin, luteolin, kaempferol, isorhamnetin and diosmetin, and to a lesser degree by rhamnetin and apigenin.

Cofactor. Binds two Mg(2+), but the interaction with the protein is mostly indirect.

Pathway. Phospholipid metabolism; phosphatidylinositol metabolism.

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

RefSeq proteins (1): NP_689416* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005522	IPK	Family
IPR038286	IPK_sf	Homologous_superfamily

Pfam: PF03770

Enzyme classification (BRENDA):

• EC 2.7.1.151 — inositol-polyphosphate multikinase (BRENDA: 9 organisms, 96 substrates, 15 inhibitors, 28 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1D-MYO-INOSITOL 1,4,5-TRISPHOSPHATE	0.0001–0.162	7
1D-MYO-INOSITOL 1,3,4,5-TETRAKISPHOSPHATE	0.0001–0.568	5
1D-MYO-INOSITOL 1,4,5,6-TETRAKISPHOSPHATE	0.0002–0.254	5
1D-MYO-INOSITOL 4,5-BISPHOSPHATE	0.006–0.03	2
ATP	0.017–0.039	2
1D-MYO-INOSITOL 1,3,4,6-TETRAKISPHOSPHATE	0.0003	1
1D-MYO-INOSITOL-1,4,5,6-TETRAKISPHOSPHATE	0.0002	1
INOSITOL (1,3,4,5)-TETRAKISPHOSPHATE	0.0001	1
INOSITOL (1,3,4,6)-TETRAKISPHOSPHATE	0.0003	1
INOSITOL (1,4,5)-TRISPHOSPHATE	0.0001	1
INOSITOL (1,4,5,6)-TETRAKISPHOSPHATE	0.0002	1

Catalyzed reactions (Rhea), 5 shown:

• 1D-myo-inositol 1,4,5,6-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+) (RHEA:11856)
• 1D-myo-inositol 1,3,4,6-tetrakisphosphate + ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + ADP + H(+) (RHEA:12717)
• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-3,4,5-trisphosphate) + ADP + H(+) (RHEA:21292)
• 1D-myo-inositol 1,4,5-trisphosphate + 2 ATP = 1D-myo-inositol 1,3,4,5,6-pentakisphosphate + 2 ADP + 2 H(+) (RHEA:32359)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol 3,4,5-triphosphate) + ADP + H(+) (RHEA:43396)

UniProt features (60 total): mutagenesis site 18, strand 11, helix 10, binding site 9, turn 5, modified residue 2, initiator methionine 1, chain 1, sequence variant 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
5W2I	X-RAY DIFFRACTION	1.6
8V6Y	X-RAY DIFFRACTION	1.7
8V71	X-RAY DIFFRACTION	1.7
6M8A	X-RAY DIFFRACTION	1.75
8V6X	X-RAY DIFFRACTION	1.75
5W2G	X-RAY DIFFRACTION	1.8
6M8B	X-RAY DIFFRACTION	1.8
6M8C	X-RAY DIFFRACTION	1.8
6M89	X-RAY DIFFRACTION	1.85
8V6Z	X-RAY DIFFRACTION	1.85
8V70	X-RAY DIFFRACTION	1.85
8V74	X-RAY DIFFRACTION	1.85
8V75	X-RAY DIFFRACTION	1.85
5W2H	X-RAY DIFFRACTION	1.9
6M88	X-RAY DIFFRACTION	1.9
8V73	X-RAY DIFFRACTION	1.9
8V76	X-RAY DIFFRACTION	1.9
8V6W	X-RAY DIFFRACTION	1.95
8V77	X-RAY DIFFRACTION	1.95
8V79	X-RAY DIFFRACTION	1.95
8V78	X-RAY DIFFRACTION	1.96
6M8D	X-RAY DIFFRACTION	2
6M8E	X-RAY DIFFRACTION	2
8V72	X-RAY DIFFRACTION	2
6E7F	X-RAY DIFFRACTION	2.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NFU5-F1	74.50	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 (9): 196; 385; 388; 75; 82; 131–133; 144; 146; 160–167

Post-translational modifications (2): 2, 7

Mutagenesis-validated functional residues (18):

Position	Phenotype
2–69	no effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated wi
78	strongly decreased enzyme activity.
82	strongly decreased enzyme activity.
144	loss of kinase activity and ability to execute necroptosis; when associated with a-146.
146	loss of kinase activity and ability to execute necroptosis; when associated with n-144.
160	strongly decreased enzyme activity.
163	moderately decreased enzyme activity.
163	decreased activity with inositol 1,4,5-trisphosphate. no effect on phosphorylation of inositol 1,3,4,5-tetrakisphosphate
164	strongly decreased enzyme activity.
164	decreased activity with inositol 1,4,5-trisphosphate. increased phosphorylation of inositol 1,3,4,5-tetrakisphosphate.
167	decreased enzyme activity.
196	decreased enzyme activity.
196	decreased activity with inositol 1,4,5-trisphosphate. increased phosphorylation of inositol 1,3,4,5-tetrakisphosphate.
279–365	no effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated wi
322–323	interferes with nuclear localization.
327–328	interferes with nuclear localization.
366–373	no effect on affinity for phosphatidylinositol 4,5-bisphosphate and mildly increased enzyme activity; when associated wi
388	loss of enzyme activity.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1855191	Synthesis of IPs in the nucleus
R-HSA-1430728	Metabolism
R-HSA-1483249	Inositol phosphate metabolism

MSigDB gene sets: 191 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_INOSITOL_PHOSPHATE_METABOLIC_PROCESS, GOBP_POLYOL_METABOLIC_PROCESS, IVANOVA_HEMATOPOIESIS_LATE_PROGENITOR, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, chr10q21, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_SMALL_MOLECULE_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_TURQUOISE_UP, GOBP_ALCOHOL_BIOSYNTHETIC_PROCESS, GOBP_POLYOL_BIOSYNTHETIC_PROCESS

GO Biological Process (6): inositol trisphosphate metabolic process (GO:0032957), inositol phosphate biosynthetic process (GO:0032958), inositol phosphate metabolic process (GO:0043647), phosphatidylinositol metabolic process (GO:0046488), necroptotic process (GO:0070266), lipid metabolic process (GO:0006629)

GO Molecular Function (15): inositol-1,4,5-trisphosphate 6-kinase activity (GO:0000823), inositol-1,4,5,6-tetrakisphosphate 3-kinase activity (GO:0000824), inositol-1,3,4,5-tetrakisphosphate 6-kinase activity (GO:0000825), ATP binding (GO:0005524), inositol-1,4,5-trisphosphate 3-kinase activity (GO:0008440), metal ion binding (GO:0046872), 1-phosphatidylinositol-4,5-bisphosphate 3-kinase activity (GO:0046934), inositol-1,3,4,6-tetrakisphosphate 5-kinase activity (GO:0047326), inositol tetrakisphosphate kinase activity (GO:0051765), flavonoid binding (GO:0097243), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), inositol phosphate kinase activity (GO:0180030)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), ciliary basal body (GO:0036064)

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 tetrakisphosphate kinase activity	3
inositol phosphate metabolic process	2
inositol trisphosphate kinase activity	2
binding	2
cellular anatomical structure	2
polyol biosynthetic process	1
organophosphate biosynthetic process	1
organophosphate metabolic process	1
polyol metabolic process	1
phosphorus metabolic process	1
programmed necrotic cell death	1
primary metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
phosphatidylinositol kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
inositol phosphate kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
kinase activity	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
microtubule organizing center	1
cilium	1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IPMK	IPPK	Q9H8X2	842
IPMK	ITPK1	Q13572	787
IPMK	PPIP5K1	Q6PFW1	718
IPMK	SRF	P11831	599
IPMK	MINPP1	Q9UNW1	574
IPMK	ITPKB	P27987	567
IPMK	MAP4K3	Q8IVH8	566
IPMK	ISYNA1	Q9NPH2	553
IPMK	ITPKA	P23677	541
IPMK	IMPA1	P29218	527
IPMK	TP53	P04637	517
IPMK	STK11	Q15831	516
IPMK	ITPKC	Q96DU7	515
IPMK	PIP5K1A	Q99755	453
IPMK	SRSF1	Q07955	395

IntAct

8 interactions, top by confidence:

A	B	Type	Score
HSF2BP	IPMK	psi-mi:“MI:0915”(physical association)	0.560
H1-2	IPMK	psi-mi:“MI:0915”(physical association)	0.400
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
CEP120	CCDC66	psi-mi:“MI:2364”(proximity)	0.270
IPMK	HSF2BP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (14): IPMK (Proximity Label-MS), IPMK (Affinity Capture-Western), IPMK (Reconstituted Complex), IPMK (Proximity Label-MS), HSF2BP (Two-hybrid), IPMK (Proximity Label-MS), IPMK (Affinity Capture-MS), IPMK (Proximity Label-MS), IPMK (Negative Genetic), IPMK (Affinity Capture-MS), IPMK (Affinity Capture-MS), IPMK (Affinity Capture-MS), IPMK (Proximity Label-MS), IPMK (Affinity Capture-RNA)

ESM2 similar proteins: A7MBL8, B3EX61, G3V7Q0, O00763, O02810, O13010, O60942, O70172, O88370, O88377, O94806, P10687, P10894, P48426, P69341, P78356, P97789, Q0P5F7, Q13613, Q15139, Q15147, Q5F356, Q5PQ01, Q5R488, Q6DIX1, Q6GL14, Q6IQ26, Q6IQE1, Q6PAL8, Q7TT16, Q80V72, Q80XI4, Q8BKC8, Q8BPM2, Q8BWW9, Q8IZH2, Q8K1Y2, Q8NFU5, Q8TBX8, Q91XU3

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

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	52
Likely benign	3
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1108 predictions. Top by Δscore:

Variant	Effect	Δscore
10:58196696:CTC:C	acceptor_gain	1.0000
10:58196697:TC:T	acceptor_gain	1.0000
10:58196697:TCC:T	acceptor_loss	1.0000
10:58196698:CC:C	acceptor_gain	1.0000
10:58196699:C:CC	acceptor_gain	1.0000
10:58196701:A:AC	acceptor_gain	1.0000
10:58199234:CCTTA:C	donor_loss	1.0000
10:58199235:CTT:C	donor_loss	1.0000
10:58199236:TTACC:T	donor_loss	1.0000
10:58199237:TACC:T	donor_loss	1.0000
10:58199238:A:AC	donor_gain	1.0000
10:58199238:ACCAT:A	donor_gain	1.0000
10:58199239:C:CC	donor_gain	1.0000
10:58199239:C:CG	donor_loss	1.0000
10:58199239:CCAT:C	donor_gain	1.0000
10:58199239:CCATC:C	donor_gain	1.0000
10:58199242:T:TA	donor_gain	1.0000
10:58199319:AACCT:A	acceptor_loss	1.0000
10:58199322:C:G	acceptor_loss	1.0000
10:58199323:T:C	acceptor_loss	1.0000
10:58216313:TAAAT:T	acceptor_gain	1.0000
10:58216318:C:CC	acceptor_gain	1.0000
10:58227037:GATTA:G	donor_loss	1.0000
10:58227038:ATTAC:A	donor_loss	1.0000
10:58227039:TTAC:T	donor_loss	1.0000
10:58227040:TAC:T	donor_loss	1.0000
10:58227041:A:T	donor_loss	1.0000
10:58227042:C:CA	donor_loss	1.0000
10:58227135:TAAAC:T	acceptor_gain	1.0000
10:58227137:AACCT:A	acceptor_loss	1.0000

AlphaMissense

2733 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:58196167:G:T	A387D	1.000
10:58196172:A:C	D385E	1.000
10:58196172:A:T	D385E	1.000
10:58196173:T:A	D385V	1.000
10:58196173:T:C	D385G	1.000
10:58196173:T:G	D385A	1.000
10:58196574:A:C	S251R	1.000
10:58196574:A:T	S251R	1.000
10:58196576:T:G	S251R	1.000
10:58216152:C:T	G180D	1.000
10:58216167:C:T	G175E	1.000
10:58216248:C:T	G148E	1.000
10:58216253:C:A	K146N	1.000
10:58216253:C:G	K146N	1.000
10:58216255:T:C	K146E	1.000
10:58216259:A:C	D144E	1.000
10:58216259:A:T	D144E	1.000
10:58216260:T:A	D144V	1.000
10:58216260:T:C	D144G	1.000
10:58216260:T:G	D144A	1.000
10:58216261:C:G	D144H	1.000
10:58237747:C:A	E86D	1.000
10:58237747:C:G	E86D	1.000
10:58237757:C:T	G83D	1.000
10:58237758:C:G	G83R	1.000
10:58237759:C:A	R82S	1.000
10:58237759:C:G	R82S	1.000
10:58237760:C:A	R82M	1.000
10:58237760:C:G	R82T	1.000
10:58237780:T:A	K75N	1.000

dbSNP variants (sampled 300 via entrez): RS1000000602 (10:58216414 G>A,C), RS1000025768 (10:58257292 C>A,G,T), RS1000038188 (10:58264639 T>A,C), RS1000057446 (10:58257529 A>C), RS1000068568 (10:58249337 C>A,G), RS1000070739 (10:58264861 A>T), RS1000083168 (10:58207071 C>T), RS1000128393 (10:58267738 T>G), RS1000224692 (10:58230015 A>C,G), RS1000255111 (10:58246059 T>A), RS1000305239 (10:58197193 C>A,G,T), RS1000350642 (10:58204048 T>G), RS1000428440 (10:58211954 T>C), RS1000432632 (10:58253186 G>C), RS1000460015 (10:58258266 T>C)

Disease associations

OMIM: gene MIM:609851 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
hereditary neuroendocrine tumor of small intestine	Supportive	Autosomal dominant

Mondo (1): hereditary neuroendocrine tumor of small intestine (MONDO:0018698)

Orphanet (0):

HPO phenotypes

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

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001725_1	Inflammatory bowel disease	8.000000e-09
GCST001762_448	Obesity-related traits	8.000000e-06
GCST002097_18	Coronary artery calcification	7.000000e-06
GCST003134_18	Cerebrospinal fluid clusterin levels	7.000000e-06
GCST004131_118	Inflammatory bowel disease	1.000000e-06
GCST004132_81	Crohn’s disease	6.000000e-07
GCST006680_2	Nonsyndromic cleft lip with or without cleft palate x sex interaction (2df test)	4.000000e-08
GCST008369_6	Plasma anti-thyroglobulin levels	2.000000e-06
GCST009391_230	Metabolite levels	9.000000e-06
GCST90002393_352	Monocyte count	4.000000e-12

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005108	arm span
EFO:0004723	coronary artery calcification
EFO:0003959	cleft lip
EFO:0008343	sex interaction measurement
EFO:0010491	glycocholate measurement
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523401 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

3 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 124,022 (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
CHEMBL50	QUERCETIN	3	74,559
CHEMBL151	LUTEOLIN	2	23,523
CHEMBL150	KAEMPFEROL	1	25,940

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

ChEMBL bioactivities

6 potent at pChembl≥5 of 8 total, top 6 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.96	IC50	1100	nM	MYRICETIN
5.66	IC50	2200	nM	ISORHAMNETIN
5.64	IC50	2300	nM	QUERCETIN
5.36	IC50	4400	nM	KAEMPFEROL
5.26	IC50	5500	nM	LUTEOLIN
5.14	IC50	7200	nM	DIOSMETIN

PubChem BioAssay actives

6 with measured affinity, of 34 total; 6 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
3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one	1572025: Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	ic50	1.1000	uM
3,5,7-trihydroxy-2-(4-hydroxy-3-methoxyphenyl)chromen-4-one	1572025: Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	ic50	2.2000	uM
Quercetin	1572025: Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	ic50	2.3000	uM
3,5,7-trihydroxy-2-(4-hydroxyphenyl)chromen-4-one	1572025: Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	ic50	4.4000	uM
2-(3,4-dihydroxyphenyl)-5,7-dihydroxychromen-4-one	1572025: Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	ic50	5.5000	uM
Diosmetin	1572025: Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	ic50	7.2000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
GSK-J4	increases expression	1
triphenyl phosphate	affects expression	1
arsenite	decreases reaction, affects binding	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
jinfukang	decreases expression	1
Leflunomide	increases expression	1
Microplastics	decreases expression, increases abundance	1
Cisplatin	increases expression	1
Endosulfan	decreases expression	1
Gold	decreases expression	1
Polyethylene Terephthalates	decreases expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Tretinoin	increases expression	1
Urethane	increases expression	1
Aflatoxin B1	decreases methylation	1
Aflatoxin M1	decreases expression	1
Cadmium Chloride	decreases expression	1
Okadaic Acid	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	affects expression	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
CHEMBL4370054	Binding	Inhibition of human IPMK using insP3 as substrate preincubated for 15 mins followed by substrate and measured after 30 mins by TR-FRET assay	Inhibition of Inositol Polyphosphate Kinases by Quercetin and Related Flavonoids: A Structure-Activity Analysis. — 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_D8NB	Ubigene HCT 116 IPMK KO	Cancer cell line	Male

Clinical trials (associated diseases)

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