PIP4K2C

Summary

PIP4K2C (phosphatidylinositol-5-phosphate 4-kinase type 2 gamma, HGNC:23786) is a protein-coding gene on chromosome 12q13.3, encoding Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma (Q8TBX8). Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic activity.

Enables 1-phosphatidylinositol-4-phosphate 5-kinase activity and identical protein binding activity. Involved in 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process; negative regulation of insulin receptor signaling pathway; and positive regulation of autophagosome assembly. Located in several cellular components, including autophagosome; cytosol; and nucleoplasm.

Source: NCBI Gene 79837 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 58 total
• Druggable target: yes — 32 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_024779

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23786
Approved symbol	PIP4K2C
Name	phosphatidylinositol-5-phosphate 4-kinase type 2 gamma
Location	12q13.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ22055
Ensembl gene	ENSG00000166908
Ensembl biotype	protein_coding
OMIM	617104
Entrez	79837

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 nonsense_mediated_decay

ENST00000354947, ENST00000422156, ENST00000540759, ENST00000548264, ENST00000550095, ENST00000550360, ENST00000550465, ENST00000551772, ENST00000923618, ENST00000923619

RefSeq mRNA: 4 — MANE Select: NM_024779 NM_001146258, NM_001146259, NM_001146260, NM_024779

CCDS: CCDS53808, CCDS55839, CCDS8946

Canonical transcript exons

ENST00000354947 — 10 exons

Exon	Start	End
ENSE00000750795	57600324	57600437
ENSE00001140569	57600811	57601078
ENSE00001263157	57601245	57601348
ENSE00001405553	57601526	57603418
ENSE00002353454	57591192	57591463
ENSE00003533251	57594025	57594122
ENSE00003535946	57599400	57599438
ENSE00003566332	57595888	57596031
ENSE00003618781	57599065	57599211
ENSE00003644345	57595126	57595222

Expression profiles

Bgee: expression breadth ubiquitous, 280 present calls, max score 96.84.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.0010 / max 168.9515, expressed in 1797 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
126279	24.1660	1794
126278	0.8349	487

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	96.84	gold quality
secondary oocyte	CL:0000655	96.09	gold quality
hair follicle	UBERON:0002073	95.97	gold quality
oocyte	CL:0000023	95.48	gold quality
renal medulla	UBERON:0000362	95.45	gold quality
CA1 field of hippocampus	UBERON:0003881	94.86	gold quality
oviduct epithelium	UBERON:0004804	94.60	gold quality
pons	UBERON:0000988	94.52	gold quality
nasal cavity epithelium	UBERON:0005384	94.12	gold quality
buccal mucosa cell	CL:0002336	93.62	gold quality
nipple	UBERON:0002030	93.44	gold quality
islet of Langerhans	UBERON:0000006	93.35	gold quality
tongue squamous epithelium	UBERON:0006919	93.08	silver quality
middle temporal gyrus	UBERON:0002771	92.98	gold quality
cardia of stomach	UBERON:0001162	92.94	gold quality
cervix squamous epithelium	UBERON:0006922	92.79	silver quality
saphenous vein	UBERON:0007318	92.76	gold quality
Brodmann (1909) area 46	UBERON:0006483	92.73	gold quality
prefrontal cortex	UBERON:0000451	92.65	gold quality
popliteal artery	UBERON:0002250	92.57	gold quality
orbitofrontal cortex	UBERON:0004167	92.57	gold quality
tibial artery	UBERON:0007610	92.56	gold quality
vena cava	UBERON:0004087	92.42	gold quality
epithelium of nasopharynx	UBERON:0001951	92.31	silver quality
trachea	UBERON:0003126	92.25	gold quality
pylorus	UBERON:0001166	92.16	gold quality
type B pancreatic cell	CL:0000169	92.10	silver quality
fallopian tube	UBERON:0003889	92.07	gold quality
olfactory bulb	UBERON:0002264	91.97	gold quality
frontal cortex	UBERON:0001870	91.90	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

miRNA regulators (miRDB)

117 targeting PIP4K2C, 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-4795-3P	100.00	74.62	4024
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4534	99.99	66.58	1907
HSA-MIR-33A-5P	99.99	68.62	1055
HSA-MIR-33B-5P	99.99	68.58	1062
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960
HSA-MIR-92B-3P	99.98	75.25	1955
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-7162-3P	99.89	68.16	1682
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-6842-5P	99.80	67.54	1587

Literature-anchored findings (GeneRIF, showing 4)

• the loss of PIP4Ks (PIP4K2A, PIP4K2B, and PIP4K2C) in vitro results in a paradoxical increase in PI(4,5)P2 and a concomitant increase in insulin-stimulated production of PI(3,4,5)P3. (PMID:31091439)
• study provides additional evidence of the involvement of members of the PIP4K2 family, in particular PIP4K2A and PIP4K2C, in AML (PMID:31109595)
• C24-Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Phosphatidylinositol 5-Phosphate 4-Kinase Type-2 Gamma to Facilitate Mammalian Target of Rapamycin Signaling Activation. (PMID:32374916)
• Loss of Pip4k2c confers liver-metastatic organotropism through insulin-dependent PI3K-AKT pathway activation. (PMID:38286827)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pip4k2ca	ENSDARG00000031020
danio_rerio	pip4k2cb	ENSDARG00000091637
mus_musculus	Pip4k2c	ENSMUSG00000025417
rattus_norvegicus	Pip4k2c	ENSRNOG00000005138

Paralogs (6): PIP5K1B (ENSG00000107242), PIP5K1A (ENSG00000143398), PIP4K2A (ENSG00000150867), PIP5KL1 (ENSG00000167103), PIP5K1C (ENSG00000186111), PIP4K2B (ENSG00000276293)

Protein

Protein identifiers

Phosphatidylinositol 5-phosphate 4-kinase type-2 gamma — Q8TBX8 (reviewed: Q8TBX8)

Alternative names: Phosphatidylinositol 5-phosphate 4-kinase type II gamma

All UniProt accessions (5): Q8TBX8, F8VNT5, F8VU68, F8VVB2, H0YIJ6

UniProt curated annotations — full annotation on UniProt →

Function. Phosphatidylinositol 5-phosphate 4-kinase with low enzymatic activity. May be a GTP sensor, has higher GTP-dependent kinase activity than ATP-dependent kinase activity. PIP4Ks negatively regulate insulin signaling through a catalytic-independent mechanism. They interact with PIP5Ks and suppress PIP5K-mediated PtdIns(4,5)P2 synthesis and insulin-dependent conversion to PtdIns(3,4,5)P3.

Subunit / interactions. Interacts with PIP5K1A; the interaction inhibits PIP5K1A kinase activity.

Subcellular location. Endoplasmic reticulum. Cytoplasm.

Post-translational modifications. Phosphorylated, phosphorylation is induced by EGF.

Isoforms (3)

UniProt ID	Names	Canonical?
Q8TBX8-1	1	yes
Q8TBX8-2	2
Q8TBX8-3	3

RefSeq proteins (4): NP_001139730, NP_001139731, NP_001139732, NP_079055* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002498	PInositol-4-P-4/5-kinase_core	Domain
IPR023610	PInositol-4/5-P-5/4-kinase	Family
IPR027483	PInositol-4-P-4/5-kinase_C_sf	Homologous_superfamily
IPR027484	PInositol-4-P-5-kinase_N	Homologous_superfamily

Pfam: PF01504

Enzyme classification (BRENDA):

• EC 2.7.1.149 — 1-phosphatidylinositol-5-phosphate 4-kinase (BRENDA: 9 organisms, 17 substrates, 83 inhibitors, 6 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0039–0.0942	6

Catalyzed reactions (Rhea), 3 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H(+) (RHEA:12280)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + GTP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + GDP + H(+) (RHEA:55964)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H(+) (RHEA:55992)

UniProt features (41 total): strand 17, helix 9, sequence variant 3, modified residue 3, turn 2, splice variant 2, initiator methionine 1, chain 1, mutagenesis site 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
7QPN	X-RAY DIFFRACTION	1.95
9U4S	X-RAY DIFFRACTION	2.25
7QIE	X-RAY DIFFRACTION	2.39
8BQ4	X-RAY DIFFRACTION	2.42
2GK9	X-RAY DIFFRACTION	2.8

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBX8-F1	81.64	0.63

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): 2, 26, 349

Mutagenesis-validated functional residues (1):

Position	Phenotype
69–75	loss of interaction with pip5k1a. loss of inhibition of pip5k1a activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-6811555	PI5P Regulates TP53 Acetylation
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8847453	Synthesis of PIPs in the nucleus

MSigDB gene sets: 197 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_UP, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GU_PDEF_TARGETS_DN, GOBP_VACUOLE_ORGANIZATION, MODULE_255, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, MODULE_317, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_VACUOLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_ORGANELLE_ORGANIZATION

GO Biological Process (8): regulation of autophagy (GO:0010506), negative regulation of insulin receptor signaling pathway (GO:0046627), phosphatidylinositol phosphate biosynthetic process (GO:0046854), 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate biosynthetic process (GO:1902635), positive regulation of autophagosome assembly (GO:2000786), lipid metabolic process (GO:0006629), regulation of signal transduction (GO:0009966), phosphatidylinositol metabolic process (GO:0046488)

GO Molecular Function (9): ATP binding (GO:0005524), 1-phosphatidylinositol-4-phosphate 5-kinase activity (GO:0016308), 1-phosphatidylinositol-5-phosphate 4-kinase activity (GO:0016309), identical protein binding (GO:0042802), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatidylinositol kinase activity (GO:0052742)

GO Cellular Component (8): nucleoplasm (GO:0005654), autophagosome (GO:0005776), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), plasma membrane (GO:0005886), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), intracellular membrane-bounded organelle (GO:0043231)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
PI Metabolism	2
Regulation of TP53 Activity through Acetylation	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
phosphatidylinositol kinase activity	2
cytoplasm	2
intracellular anatomical structure	2
autophagy	1
regulation of catabolic process	1
insulin receptor signaling pathway	1
negative regulation of signal transduction	1
regulation of insulin receptor signaling pathway	1
negative regulation of cellular response to insulin stimulus	1
glycerophospholipid biosynthetic process	1
phosphatidylinositol phosphate biosynthetic process	1
1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate metabolic process	1
autophagosome assembly	1
positive regulation of macroautophagy	1
positive regulation of vacuole organization	1
positive regulation of organelle assembly	1
regulation of autophagosome assembly	1
primary metabolic process	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
phosphorus metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
lipid kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
nuclear lumen	1
vacuole	1
endomembrane system	1
intracellular membrane-bounded organelle	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

1194 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIP4K2C	KIF5A	Q12840	729
PIP4K2C	MYL6B	P14649	671
PIP4K2C	PADI4	Q9UM07	658
PIP4K2C	PDE1B	Q01064	639
PIP4K2C	OLIG3	Q7RTU3	626
PIP4K2C	TNFRSF14	Q92956	573
PIP4K2C	PI4KB	P78405	555
PIP4K2C	MMEL1	Q495T6	551
PIP4K2C	PTPN22	Q9Y2R2	509
PIP4K2C	GINM1	Q9NU53	504
PIP4K2C	TRAF1	Q13077	479
PIP4K2C	ZNF275	Q9NSD4	472
PIP4K2C	TNFAIP3	P21580	461
PIP4K2C	IL26	Q9NPH9	452
PIP4K2C	RNF216	Q9NWF9	451

IntAct

121 interactions, top by confidence:

A	B	Type	Score
TP53	MDM2	psi-mi:“MI:0914”(association)	1.000
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
HIF1AN	APBA3	psi-mi:“MI:0914”(association)	0.850
EAF1	ELL2	psi-mi:“MI:0914”(association)	0.840
PIP4K2A	AHCYL1	psi-mi:“MI:0914”(association)	0.730
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
HIF1AN	GMDS	psi-mi:“MI:0914”(association)	0.640
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
STK11	KDM4A	psi-mi:“MI:0914”(association)	0.640
ZRANB2	PIP4K2A	psi-mi:“MI:0914”(association)	0.610
PIP4K2C	PIP4K2C	psi-mi:“MI:0407”(direct interaction)	0.530
SUN2	POTEF	psi-mi:“MI:0914”(association)	0.530
DNAAF8	CCDC85C	psi-mi:“MI:0914”(association)	0.530
APBA3	DUSP11	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
GSPT2	IGF2BP3	psi-mi:“MI:0914”(association)	0.530
PRICKLE3	SIAH2	psi-mi:“MI:0914”(association)	0.530
PIP4K2B	AHCYL1	psi-mi:“MI:0914”(association)	0.530
GPBP1L1	CNOT1	psi-mi:“MI:0914”(association)	0.530

BioGRID (589): PIP4K2C (Affinity Capture-MS), PIP4K2C (Affinity Capture-MS), PIP4K2C (Affinity Capture-MS), PIP4K2C (Affinity Capture-MS), PIP4K2C (Affinity Capture-MS), PIP4K2C (Co-fractionation), PIP4K2C (Co-fractionation), PIP4K2C (Co-fractionation), PIP4K2C (Co-fractionation), PIP4K2C (Co-fractionation), PIP4K2C (Co-fractionation), PIP4K2C (Co-fractionation), SKP1 (Co-fractionation), PIP4K2C (Affinity Capture-MS), PIP4K2C (Affinity Capture-MS)

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: A2A3N6, D3ZSI8, O13853, O14986, O17453, O35226, O48709, O60331, O61742, O70161, O82143, O88370, O88377, O94444, P38886, P38994, P55034, P55035, P55036, P70181, P70182, P78356, Q0P5F7, Q553E0, Q55GN6, Q56YP2, Q58DA0, Q5CZZ9, Q5F356, Q5I6B8, Q5PQ01, Q5R488, Q5ZJ58, Q6EX42, Q6GL14, Q6IQE1, Q80XI4, Q8I239, Q8L796, Q8L850

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
mTORC1	“up-regulates quantity”	PIP4K2C	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2226 predictions. Top by Δscore:

Variant	Effect	Δscore
12:57594119:ACAGG:A	donor_loss	1.0000
12:57594120:CAGGT:C	donor_loss	1.0000
12:57594121:AGGTA:A	donor_loss	1.0000
12:57594122:GGT:G	donor_loss	1.0000
12:57594124:T:A	donor_loss	1.0000
12:57595953:C:CA	acceptor_gain	1.0000
12:57595953:C:G	acceptor_gain	1.0000
12:57599058:A:AG	acceptor_gain	1.0000
12:57599058:ACT:A	acceptor_gain	1.0000
12:57599059:C:G	acceptor_gain	1.0000
12:57599060:T:A	acceptor_gain	1.0000
12:57599062:TAGT:T	acceptor_loss	1.0000
12:57599063:A:AG	acceptor_gain	1.0000
12:57599064:G:GT	acceptor_gain	1.0000
12:57599064:GT:G	acceptor_gain	1.0000
12:57599064:GTA:G	acceptor_gain	1.0000
12:57599064:GTAC:G	acceptor_gain	1.0000
12:57599064:GTACA:G	acceptor_gain	1.0000
12:57599196:G:GT	donor_gain	1.0000
12:57599196:G:T	donor_gain	1.0000
12:57599210:AG:A	donor_gain	1.0000
12:57599211:GG:G	donor_gain	1.0000
12:57599212:G:GG	donor_gain	1.0000
12:57599212:G:T	donor_loss	1.0000
12:57600435:G:GT	donor_gain	1.0000
12:57600962:T:TA	acceptor_gain	1.0000
12:57601079:G:GA	donor_loss	1.0000
12:57601080:T:A	donor_loss	1.0000
12:57601242:CA:C	acceptor_loss	1.0000
12:57601243:A:AG	acceptor_gain	1.0000

AlphaMissense

2798 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:57595185:T:C	L111P	1.000
12:57595188:G:C	R112P	1.000
12:57599207:T:A	L219H	1.000
12:57599207:T:C	L219P	1.000
12:57599209:A:G	K220E	1.000
12:57599211:G:C	K220N	1.000
12:57599211:G:T	K220N	1.000
12:57599400:G:C	G221R	1.000
12:57599400:G:T	G221C	1.000
12:57599401:G:A	G221D	1.000
12:57599416:G:C	R226P	1.000
12:57600345:A:G	K241E	1.000
12:57600347:G:C	K241N	1.000
12:57600347:G:T	K241N	1.000
12:57600348:G:C	D242H	1.000
12:57600358:T:C	F245S	1.000
12:57600845:T:C	L283P	1.000
12:57601329:C:A	A389D	1.000
12:57601562:T:C	Y408H	1.000
12:57601583:T:C	F415L	1.000
12:57601585:T:A	F415L	1.000
12:57601585:T:G	F415L	1.000
12:57591449:G:C	G54R	0.999
12:57591450:G:A	G54D	0.999
12:57594076:T:C	F76L	0.999
12:57594077:T:C	F76S	0.999
12:57594078:T:A	F76L	0.999
12:57594078:T:G	F76L	0.999
12:57595145:T:C	F98L	0.999
12:57595147:C:A	F98L	0.999

dbSNP variants (sampled 300 via entrez): RS1000692519 (12:57597227 C>T), RS1000854418 (12:57600543 C>A,T), RS1000929405 (12:57600131 G>C,T), RS1000953778 (12:57597477 A>G), RS1001090524 (12:57593572 C>T), RS1001160800 (12:57591120 C>T), RS1001543090 (12:57593851 G>C), RS1001638897 (12:57603538 A>C), RS1001709852 (12:57596914 G>T), RS1001742416 (12:57596672 C>T), RS1002050119 (12:57598164 A>G), RS1002081113 (12:57597835 G>A), RS1002659209 (12:57591715 T>G), RS1002826379 (12:57592690 G>A,T), RS1002931301 (12:57603463 T>C)

Disease associations

OMIM: gene MIM:617104 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST000232_9	Rheumatoid arthritis	9.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1770034 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

32 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 477,239 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL2103830	FOSTAMATINIB	4	3,841
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL3353410	OSIMERTINIB	4	8,898
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL939	GEFITINIB	4	117,814
CHEMBL941	IMATINIB	4	111,611
CHEMBL1091644	LINSITINIB	3	1,446
CHEMBL2087361	ICOTINIB	3	2,802
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1236962	OMIPALISIB	2	3,989
CHEMBL1822792	MK-2461	2	686
CHEMBL206834	BAFETINIB	2	1,024
CHEMBL230011	TG100-115	2	1,504
CHEMBL3120215	OSI-027	2	1,854
CHEMBL3218578	BGT-226 FREE BASE	2
CHEMBL4303241	BAY-1161909	2
CHEMBL475251	R-406	2
CHEMBL513909	BI-2536	2
CHEMBL564829	MILCICLIB	2
CHEMBL1236107	SGX-523	1
CHEMBL1908394	GSK-461364	1
CHEMBL2133806	JNJ-38877605	1
CHEMBL3544966	GSK-1059615	1
CHEMBL3545083	RGB-286638	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol phosphate kinases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
TMX-4102	Binding	9.35	pKd
TMX-4153	Binding	7.38	pKd
RMC-113	Binding	7.34	pKd

Binding affinities (BindingDB)

41 measured of 247 human assays (247 total across all organisms); most potent 41 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
4-((4-([1,1’-biphenyl]-3-yl)-5-chloropyrimidin-2-yl)amino)cyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-4-((5-chloro-4-(4-fluorophenyl)pyrimidin-2-yl)amino)cyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(3-((5-chloro-4-(4-fluorophenyl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-chloro-4-(4-fluorophenyl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
N-(cis-4-((4-([1,1’-biphenyl]-3-yl)-5-chloropyrimidin-2-yl)amino)cyclohexyl)acetamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-3-((5-fluoro-4-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)cyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-N-(4-((5-chloro-4-(1-cyclopropyl-6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)amino)cyclohexyl)acetamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-N-(4-((5-chloro-4-(1-cyclopropyl-1H-pyrazole-4-yl)pyrimidin-2-yl)amino)cyclohexyl)acetamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-4-((5-chloro-4-(1-cyclopropyl-6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-4-((5-chloro-4-(1-cyclopropyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-3-((5-chloro-4-(1-(4-fluorophenyl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclobutane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-chloro-4-(1-(4-fluorobenzoyl)pyrrolidin-3-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-3-((5-chloro-4-(1-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclobutane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
(S)-5-(2-((1-acetylpiperidin-3-yl)amino)-5-chloropyrimidin-4-yl)-1-(4-fluorophenyl)pyridin-2(1H)-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-4-((5-chloro-4-(1-(6-oxo-1,6-dihydropyridin-3-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-4-((5-chloro-4-(1-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-4-((5-chloro-4-(1-(6-oxo-1,6-dihydropyridin-2-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
5-(1-(2-((1-acetylpiperidin-4-yl)amino)-5-fluoropyrimidin-4-yl)piperidin-3-yl)pyridin-2(1H)-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-fluoro-4-morpholinopyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-fluoro-4-((S)-3-((R)-3-hydroxypyrrolidine-1-carbonyl)piperidin-1-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
4-(1-(2-((1-acetylpiperidin-4-yl)amino)-5-fluoropyrimidin-4-yl)piperidin-3-yl)pyridin-2(1H)-one	KD	750 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-((3S)-3-((5-chloro-4-(3-phenylpyrrolidin-1-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-chloro-4-(piperidin-1-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-3-((5-chloro-4-(4-fluorophenyl)pyrimidin-2-yl)amino)cyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-((3S)-3-((5-chloro-4-(3-(pyridin-2-yl)pyrrolidin-1-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-3-((5-fluoro-4-(1-(4-fluorophenyl)-1H-pyrazol-3-yl)pyrimidin-2-yl)amino)cyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-4-((5-chloro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridin-3-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-4-((5-chloro-4-(1-cyclohexyl-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-[4-[[5-chloro-4-(1-cyclohexylpyrazol-3-yl)pyrimidin-2-yl]amino]-1-piperidyl]ethanone	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-3-((4-(1-cyclohexyl-1H-pyrazol-3-yl)-5-fluoropyrimidin-2-yl)amino)cyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-chloro-4-(1-(4-fluorobenzoyl)piperidin-3-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-N-(4-((5-chloro-4-(1-(4-fluorobenzoyl)pyrrolidin-3-yl)pyrimidin-2-yl)amino)cyclohexyl)acetamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-4-((5-chloro-4-(5-cyclopropyl-1H-pyrazol-3-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
cis-4-((5-chloro-4-(1-(2-oxo-1,2-dihydropyridin-4-yl)-1H-pyrazol-4-yl)pyrimidin-2-yl)amino)-N-methylcyclohexane-1-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-N-(4-((5-fluoro-4-morpholinopyrimidin-2-yl)amino)cyclohexyl)acetamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(1-(2-((1-acetylpiperidin-4-yl)amino)-5-fluoropyrimidin-4-yl)piperidin-3-yl)pyridin-2(1H)-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
(S)-1-(3-((5-chloro-4-(6-(4-fluorophenyl)pyridin-2-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-(R)-1-(2-((4-acetamidocyclohexyl)amino)-5-fluoropyrimidin-4-yl)-N-cyclopropylpiperidine-3-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-(S)-1-(2-((4-acetamidocyclohexyl)amino)-5-fluoropyrimidin-4-yl)-N-cyclopropylpiperidine-3-carboxamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
1-(4-((5-fluoro-4-((S)-3-((S)-3-hydroxypyrrolidine-1-carbonyl)piperidin-1-yl)pyrimidin-2-yl)amino)piperidin-1-yl)ethan-1-one	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN
trans-N-(4-((5-fluoro-4-(4-(2-oxopyridin-1(2H)-yl)-1H-pyrazol-1-yl)pyrimidin-2-yl)amino)cyclohexyl)acetamide	KD	3000 nM	WO-2024233846: INHIBITORS AND DEGRADERS OF PIP4K PROTEIN

ChEMBL bioactivities

186 potent at pChembl≥5 of 211 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.64	Kd	0.023	nM	CHEMBL4454033
8.80	Kd	1.6	nM	CHEMBL4436648
8.52	Kd	3	nM	CHEMBL3688339
8.47	Kd	3.4	nM	CHEMBL4455633
8.32	Kd	4.8	nM	CHEMBL4446338
8.28	Kd	5.258	nM	CHEMBL5653589
8.24	ED50	5.797	nM	CHEMBL5653589
8.15	Kd	7.1	nM	CHEMBL5440409
8.10	IC50	7.943	nM	CHEMBL5420914
8.10	IC50	7.943	nM	CHEMBL5394000
7.90	IC50	12.59	nM	CHEMBL5405402
7.90	IC50	12.59	nM	CHEMBL5399468
7.90	IC50	12.59	nM	CHEMBL5427550
7.90	IC50	12.59	nM	CHEMBL5426348
7.80	IC50	15.85	nM	CHEMBL5425953
7.70	IC50	19.95	nM	CHEMBL5431778
7.70	IC50	19.95	nM	CHEMBL5405966
7.70	IC50	19.95	nM	CHEMBL5400154
7.70	IC50	19.95	nM	CHEMBL5423670
7.70	IC50	19.95	nM	CHEMBL5405402
7.60	IC50	25.12	nM	CHEMBL5424397
7.55	Kd	28	nM	FORETINIB
7.50	IC50	31.62	nM	CHEMBL5413364
7.50	IC50	31.62	nM	CHEMBL5415354
7.50	IC50	31.62	nM	CHEMBL5399847
7.47	Kd	34	nM	CHEMBL4554938
7.47	Kd	34	nM	CHEMBL5423303
7.40	IC50	39.81	nM	CHEMBL5422736
7.40	IC50	39.81	nM	CHEMBL5399032
7.40	IC50	39.81	nM	CHEMBL5400049
7.40	IC50	39.81	nM	CHEMBL5426348
7.30	IC50	50.12	nM	CHEMBL5397186
7.30	IC50	50.12	nM	CHEMBL5428289
7.30	IC50	50.12	nM	CHEMBL5402305
7.30	IC50	50.12	nM	CHEMBL5436163
7.30	IC50	50.12	nM	CHEMBL5415385
7.30	IC50	50.12	nM	CHEMBL5412191
7.30	IC50	50.12	nM	CHEMBL5405966
7.30	IC50	50.12	nM	CHEMBL5420914
7.20	IC50	63.1	nM	CHEMBL5428618
7.19	Kd	65	nM	CHEMBL5441057
7.17	Kd	67	nM	CYC-116
7.17	Kd	68	nM	CHEMBL5085734
7.17	Kd	67	nM	CHEMBL5426728
7.11	Kd	77	nM	CHEMBL5406257
7.10	IC50	79.43	nM	CHEMBL5410975
7.10	IC50	79.43	nM	CHEMBL5427550
7.00	IC50	100	nM	CHEMBL5403647
7.00	IC50	100	nM	CHEMBL5397757
7.00	IC50	100	nM	CHEMBL5413329

PubChem BioAssay actives

136 with measured affinity, of 611 total; 50 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
N-[4-[2-amino-5-[(Z)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]phenyl]methanesulfonamide	1607160: Binding affinity to human PI5P4IKgamma	kd	<0.0001	uM
N-[4-[5-[(Z)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]phenyl]methanesulfonamide	1607160: Binding affinity to human PI5P4IKgamma	kd	0.0016	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425115: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0030	uM
N-[4-[5-(1H-indol-4-yl)-3-pyridinyl]phenyl]methanesulfonamide	1607160: Binding affinity to human PI5P4IKgamma	kd	0.0034	uM
4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]benzamide	1607160: Binding affinity to human PI5P4IKgamma	kd	0.0048	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149014: Binding affinity to human PIP4K2C incubated for 45 mins by Kinobead based pull down assay	kd	0.0053	uM
N-[4-[(6-methylthieno[2,3-d]pyrimidin-4-yl)amino]phenyl]methanesulfonamide	1973288: Binding affinity to wild type human PI5P4Kgamma assessed as dissociation constant incubated for 30 mins by DiscoverX KINOMEscan assay	kd	0.0071	uM
6-(2-chloro-3-pyridinyl)-N-(4-methylsulfanylphenyl)thieno[3,2-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0079	uM
1-[4-[[6-(2-methyl-3-pyridinyl)thieno[3,2-d]pyrimidin-4-yl]amino]phenyl]pyrrolidin-2-one	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0079	uM
6-(4-methyl-3-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0126	uM
6-(3-methyl-4-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0126	uM
6-(2-chloro-3-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[3,2-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0126	uM
6-(2-chloro-3-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0126	uM
N-(4-methylsulfonylphenyl)-6-(1H-pyrazol-4-yl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0158	uM
6-(3-methyl-4-pyridinyl)-N-(4-methylsulfanylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0199	uM
6-(2-methyl-3-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0199	uM
6-(2-chloro-3-pyridinyl)-N-(4-methylsulfanylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0199	uM
N-(4-methylsulfonylphenyl)-6-pyridin-4-ylthieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0199	uM
6-(3,5-dimethyl-1,2-oxazol-4-yl)-N-(4-methylsulfanylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0251	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	625134: Binding constant for PIP5K2C kinase domain	kd	0.0280	uM
6-(2-fluoro-3-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0316	uM
N-(4-methylsulfonylphenyl)-6-pyridin-3-ylthieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0316	uM
6-(3-methoxy-4-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0316	uM
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide	2189156: Binding affinity to PIP5K2C (unknown origin) assessed as dissociation constant	kd	0.0340	uM
4-acetamido-N-[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]benzamide	2002939: Binding affinity to full length wild type human PI5P4Kgamma assessed as dissociation constant by KINOMEscan KdELECT assay	kd	0.0340	uM
N-(4-methylsulfanylphenyl)-6-(1,2-oxazol-4-yl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0398	uM
6-(1-methylpyrazol-4-yl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0398	uM
N-(4-methylsulfonylphenyl)-6-phenylthieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0398	uM
5-chloro-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0501	uM
6-(2-methyl-3-pyridinyl)-N-(4-methylsulfanylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0501	uM
N-(4-methylsulfonylphenyl)thieno[3,2-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0501	uM
N-(4-cyclopropylphenyl)-6-(2-methyl-3-pyridinyl)thieno[3,2-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0501	uM
5-methyl-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0501	uM
N-methyl-4-(4-methylsulfonylanilino)-N-phenylthieno[2,3-d]pyrimidine-5-carboxamide	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0501	uM
6-(2-chloro-4-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0631	uM
1-N-[7-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-7-oxoheptyl]-4-N-[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]benzene-1,4-dicarboxamide	2002939: Binding affinity to full length wild type human PI5P4Kgamma assessed as dissociation constant by KINOMEscan KdELECT assay	kd	0.0650	uM
1-N-[3-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-3-oxopropyl]-4-N-[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]benzene-1,4-dicarboxamide	2002939: Binding affinity to full length wild type human PI5P4Kgamma assessed as dissociation constant by KINOMEscan KdELECT assay	kd	0.0670	uM
4-methyl-5-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]-1,3-thiazol-2-amine	1425115: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0670	uM
5-methyl-2-(2-propan-2-ylphenyl)-N-(pyridin-2-ylmethyl)pyrrolo[3,2-d]pyrimidin-4-amine	1823112: Binding affinity to PI5P4Kgamma (unknown origin) by KINOMEscan analysis	kd	0.0680	uM
1-N-[4-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-4-oxobutyl]-4-N-[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]benzene-1,4-dicarboxamide	2002939: Binding affinity to full length wild type human PI5P4Kgamma assessed as dissociation constant by KINOMEscan KdELECT assay	kd	0.0770	uM
6-methyl-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.0794	uM
N-(4-cyclopropylphenyl)-6-(2-methyl-3-pyridinyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.1000	uM
6-(3-fluoro-4-pyridinyl)-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.1000	uM
5-cyclopropyl-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.1000	uM
6-(2-methyl-3-pyridinyl)-N-[4-(pentafluoro-lambda6-sulfanyl)phenyl]thieno[3,2-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.1000	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	625134: Binding constant for PIP5K2C kinase domain	kd	0.1100	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	625134: Binding constant for PIP5K2C kinase domain	kd	0.1200	uM
N’-[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-N-[4-[[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]carbamoyl]phenyl]butanediamide	2002939: Binding affinity to full length wild type human PI5P4Kgamma assessed as dissociation constant by KINOMEscan KdELECT assay	kd	0.1500	uM
5,6-dimethyl-N-(4-methylsulfonylphenyl)thieno[2,3-d]pyrimidin-4-amine	2003977: Inhibition of GST-fused human recombinant chimeric PI5P4Kgamma+ harboring PI5P4Kalpha-like mutations expressed in Escherichia coli BL21(DE3) incubated for 60 mins by ADP-Glo assay	ic50	0.1995	uM
N’-[(2S)-1-[(2S,4R)-4-hydroxy-2-[[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]carbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]-N-[4-[[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]carbamoyl]phenyl]decanediamide	2002939: Binding affinity to full length wild type human PI5P4Kgamma assessed as dissociation constant by KINOMEscan KdELECT assay	kd	0.2200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases expression	3
bisphenol A	affects expression, decreases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
aristolochic acid I	increases expression	1
dicrotophos	increases expression	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	increases expression	1
trichostatin A	affects expression	1
tetrabromobisphenol A	increases expression	1
CGP 52608	affects binding, increases reaction	1
tanespimycin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	increases expression	1
hexabrominated diphenyl ether 153	increases expression	1
VER 155008	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases response to substance	1
Acetaminophen	increases expression	1
Calcitriol	increases expression	1
Diethylstilbestrol	increases expression	1
Dimethyl Sulfoxide	increases expression	1
Ethyl Methanesulfonate	increases expression	1
Folic Acid	increases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Potassium Dichromate	increases expression	1
Smoke	decreases expression	1
Tretinoin	affects cotreatment, decreases expression	1
Urethane	increases expression	1

ChEMBL screening assays

179 unique, capped per target: 179 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1175219	Binding	Inhibition of PIP5K2C at 10 uM	Broad spectrum alkynyl inhibitors of T315I Bcr-Abl. — Bioorg Med Chem Lett

Cellosaurus cell lines

6 cell lines: 5 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AU	Abcam HeLa PIP4K2C KO	Cancer cell line	Female
CVCL_D7XJ	Ubigene A-549 PIP4K2C KO	Cancer cell line	Male
CVCL_D8T0	Ubigene HCT 116 PIP4K2C KO	Cancer cell line	Male
CVCL_D9NH	Ubigene HEK293 PIP4K2C KO	Transformed cell line	Female
CVCL_E0KU	Ubigene HeLa PIP4K2C KO	Cancer cell line	Female
CVCL_TD91	HAP1 PIP4K2C (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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