PIP4K2B

Summary

PIP4K2B (phosphatidylinositol-5-phosphate 4-kinase type 2 beta, HGNC:8998) is a protein-coding gene on chromosome 17q12, encoding Phosphatidylinositol 5-phosphate 4-kinase type-2 beta (P78356). Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.

The protein encoded by this gene catalyzes the phosphorylation of phosphatidylinositol-5-phosphate on the fourth hydroxyl of the myo-inositol ring to form phosphatidylinositol-5,4-bisphosphate. This gene is a member of the phosphatidylinositol-5-phosphate 4-kinase family. The encoded protein sequence does not show similarity to other kinases, but the protein does exhibit kinase activity. Additionally, the encoded protein interacts with p55 TNF receptor.

Source: NCBI Gene 8396 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 48 total — 1 likely-pathogenic
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_003559

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8998
Approved symbol	PIP4K2B
Name	phosphatidylinositol-5-phosphate 4-kinase type 2 beta
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	PIP5KIIB, PIP5KIIbeta
Ensembl gene	ENSG00000276293
Ensembl biotype	protein_coding
OMIM	603261
Entrez	8396

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000613767, ENST00000617499, ENST00000617781, ENST00000619039, ENST00000862415

RefSeq mRNA: 1 — MANE Select: NM_003559 NM_003559

CCDS: CCDS11329

Canonical transcript exons

ENST00000613180 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 98.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 17.1245 / max 220.5575, expressed in 1803 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165558	8.6691	1748
165559	8.4553	1715

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	98.50	gold quality
ganglionic eminence	UBERON:0004023	96.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	96.39	gold quality
right frontal lobe	UBERON:0002810	96.33	gold quality
anterior cingulate cortex	UBERON:0009835	96.32	gold quality
prefrontal cortex	UBERON:0000451	95.46	gold quality
ventricular zone	UBERON:0003053	95.44	gold quality
cerebellar hemisphere	UBERON:0002245	95.03	gold quality
cerebellar cortex	UBERON:0002129	94.98	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.96	gold quality
muscle of leg	UBERON:0001383	94.43	gold quality
hindlimb stylopod muscle	UBERON:0004252	94.27	gold quality
calcaneal tendon	UBERON:0003701	94.24	gold quality
gastrocnemius	UBERON:0001388	94.05	gold quality
amygdala	UBERON:0001876	93.92	gold quality
stromal cell of endometrium	CL:0002255	93.79	gold quality
nucleus accumbens	UBERON:0001882	93.31	gold quality
hypothalamus	UBERON:0001898	93.31	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.00	gold quality
cerebellum	UBERON:0002037	92.77	gold quality
sural nerve	UBERON:0015488	92.59	gold quality
smooth muscle tissue	UBERON:0001135	92.55	gold quality
putamen	UBERON:0001874	92.53	gold quality
right ovary	UBERON:0002118	92.01	gold quality
left ovary	UBERON:0002119	91.91	gold quality
caudate nucleus	UBERON:0001873	91.80	gold quality
body of uterus	UBERON:0009853	91.39	gold quality
right coronary artery	UBERON:0001625	91.28	gold quality
buccal mucosa cell	CL:0002336	91.11	silver quality
adrenal tissue	UBERON:0018303	91.01	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-75688	yes	434.17
E-ENAD-17	no	536.00
E-ANND-3	no	0.74

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

211 targeting PIP4K2B, 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-6833-3P	100.00	70.63	3197
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-371B-5P	99.99	75.34	4759

Literature-anchored findings (GeneRIF, showing 12)

• PIPkin IIbeta is expressed as a tagged protein, is active as revealed by immunoprecipitation and enzyme assay, and that cellular fractionation reveals that it is indeed nuclear. (PMID:17303380)
• These results indicate that PIPKIIbeta-mediated PI(4,5)P(2) signaling is important for E-cadherin upregulation and inhibition of cellular motility induced by VDR activation. (PMID:21514270)
• Association between low PIP4K2B expression and poor patient survival.Analysis of gene expression datasets confirmed the association between low PIP4K2B and low CDH1expression. (PMID:24127122)
• Knocking down PI5P4Kalpha and beta in a breast cancer cell line bearing an amplification of the gene encoding PI5P4K beta and deficient for p53 impaired growth on plastic and in xenografts. (PMID:24209622)
• Suppression of PIP4K expression selectively prevents tumor cell growth in vitro and prevents tumor development in mice that have lost the tumor suppressor p53. (Review) (PMID:25728392)
• PIP4K2B couples the cellular GTP concentration to the levels of the stress-regulated phosphoinositide PtdIns5P, to impact on tumor cell growth. (PMID:27132569)
• 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)
• MiR-3064, a key oncogenic miRNA, could promote PC cell growth, invasion and sphere formation via downregulating the levels of tumor suppressor PIP4K2B. (PMID:31488171)
• Pharmacological inhibition of PI5P4Kalpha/beta disrupts cell energy metabolism and selectively kills p53-null tumor cells. (PMID:34001596)
• Functional molecular evolution of a GTP sensing kinase: PI5P4Kbeta. (PMID:36856076)
• PIP4K2B is mechanoresponsive and controls heterochromatin-driven nuclear softening through UHRF1. (PMID:36918565)
• Autoantibodies against PIP4K2B and AKT3 Are Associated with Skin and Lung Fibrosis in Patients with Systemic Sclerosis. (PMID:36982700)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Pip4k2b	ENSMUSG00000018547
rattus_norvegicus	Pip4k2b	ENSRNOG00000013030

Paralogs (6): PIP5K1B (ENSG00000107242), PIP5K1A (ENSG00000143398), PIP4K2A (ENSG00000150867), PIP4K2C (ENSG00000166908), PIP5KL1 (ENSG00000167103), PIP5K1C (ENSG00000186111)

Protein

Protein identifiers

Phosphatidylinositol 5-phosphate 4-kinase type-2 beta — P78356 (reviewed: P78356)

Alternative names: 1-phosphatidylinositol 5-phosphate 4-kinase 2-beta, Diphosphoinositide kinase 2-beta, Phosphatidylinositol 5-phosphate 4-kinase type II beta, PtdIns(5)P-4-kinase isoform 2-beta

All UniProt accessions (2): P78356, A0A087WT35

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. Preferentially utilizes GTP, rather than ATP, for PI(5)P phosphorylation and its activity reflects changes in direct proportion to the physiological GTP concentration. Its GTP-sensing activity is critical for metabolic adaptation. 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. Homodimer. Binds TNFRSF1A. Interacts with PIP4K2A; the interaction suppresses ubiquitination by the SPOP/CUL3 complex.

Subcellular location. Endoplasmic reticulum membrane. Cell membrane. Nucleus. Cytoplasm.

Tissue specificity. Highly expressed in brain, heart, pancreas, skeletal muscle and kidney. Detected at lower levels in placenta, lung and liver.

Post-translational modifications. Ubiquitinated by the SPOP/CUL3 complex. Ubiquitination is stimulated by PtdIns5P levels. Phosphorylated on serine residues.

Isoforms (2)

UniProt ID	Names	Canonical?
P78356-1	1	yes
P78356-2	2

RefSeq proteins (1): NP_003550* (*=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 (52 total): strand 20, helix 9, modified residue 7, binding site 5, turn 4, splice variant 2, initiator methionine 1, chain 1, sequence conflict 1, domain 1, region of interest 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
3X01	X-RAY DIFFRACTION	2.15
3X02	X-RAY DIFFRACTION	2.45
3X05	X-RAY DIFFRACTION	2.5
7N80	X-RAY DIFFRACTION	2.5
3X0C	X-RAY DIFFRACTION	2.55
6K4H	X-RAY DIFFRACTION	2.55
3WZZ	X-RAY DIFFRACTION	2.6
3X04	X-RAY DIFFRACTION	2.6
3X07	X-RAY DIFFRACTION	2.6
3X0A	X-RAY DIFFRACTION	2.6
3X0B	X-RAY DIFFRACTION	2.6
7EM2	X-RAY DIFFRACTION	2.6
3X06	X-RAY DIFFRACTION	2.65
7EM1	X-RAY DIFFRACTION	2.65
3X03	X-RAY DIFFRACTION	2.7
3X09	X-RAY DIFFRACTION	2.7
6K4G	X-RAY DIFFRACTION	2.7
7N81	X-RAY DIFFRACTION	2.7
3X08	X-RAY DIFFRACTION	2.75
7EM4	X-RAY DIFFRACTION	2.8
7EM5	X-RAY DIFFRACTION	2.8
7EM6	X-RAY DIFFRACTION	2.95
1BO1	X-RAY DIFFRACTION	3
7EM8	X-RAY DIFFRACTION	3.05
7EM3	X-RAY DIFFRACTION	3.1
7EM7	X-RAY DIFFRACTION	3.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78356-F1	85.28	0.69

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 (5): 202–204; 203–204; 214; 214; 369

Post-translational modifications (7): 8, 19, 94, 150, 322, 326, 2

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: 277 (showing top): RNGTGGGC_UNKNOWN, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_VACUOLE_ORGANIZATION, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_VESICLE_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_VACUOLE_ORGANIZATION, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_RESPONSE_TO_INSULIN_STIMULUS, GOBP_MEMBRANE_FUSION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT

GO Biological Process (10): cell surface receptor signaling pathway (GO:0007166), regulation of autophagy (GO:0010506), negative regulation of insulin receptor signaling pathway (GO:0046627), phosphatidylinositol phosphate biosynthetic process (GO:0046854), autophagosome-lysosome fusion (GO:0061909), 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 (10): ATP binding (GO:0005524), GTP binding (GO:0005525), 1-phosphatidylinositol-4-phosphate 5-kinase activity (GO:0016308), 1-phosphatidylinositol-5-phosphate 4-kinase activity (GO:0016309), protein homodimerization activity (GO:0042803), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatidylinositol kinase activity (GO:0052742)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), autophagosome (GO:0005776), endoplasmic reticulum membrane (GO:0005789), cytosol (GO:0005829), plasma membrane (GO:0005886), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), membrane (GO:0016020)

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	4
signal transduction	2
purine ribonucleoside triphosphate binding	2
phosphatidylinositol kinase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	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
vesicle fusion	1
macroautophagy	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
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
phosphorus metabolic process	1
adenyl ribonucleotide binding	1
guanyl ribonucleotide binding	1
identical protein binding	1
protein dimerization activity	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

Protein interactions and networks

STRING

1318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIP4K2B	RFK	Q969G6	647
PIP4K2B	PIKFYVE	Q9Y2I7	535
PIP4K2B	PI4KB	P78405	502
PIP4K2B	PIP5K1C	O60331	476
PIP4K2B	TRADD	Q15628	426
PIP4K2B	CSNK2B	P07312	425
PIP4K2B	TNFRSF1A	P19438	424
PIP4K2B	EPOR	P19235	423
PIP4K2B	CFLAR	O15519	420
PIP4K2B	CDKL1	Q00532	419
PIP4K2B	RGS7BP	Q6MZT1	412
PIP4K2B	TANC1	Q9C0D5	411
PIP4K2B	SBK1	Q52WX2	411
PIP4K2B	ALDH1A3	P47895	410
PIP4K2B	PHF24	Q9UPV7	406

IntAct

112 interactions, top by confidence:

A	B	Type	Score
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
LIN7A	CASK	psi-mi:“MI:0914”(association)	0.830
STK11	HSP90AA1	psi-mi:“MI:0914”(association)	0.740
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
NEMP1	RGPD8	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
HMBOX1	PIP4K2B	psi-mi:“MI:0915”(physical association)	0.560
SPRY4	PIP4K2B	psi-mi:“MI:0915”(physical association)	0.560
SUN2	POTEF	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	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 (215): HMBOX1 (Two-hybrid), PIP4K2B (Affinity Capture-MS), PIP4K2B (Affinity Capture-MS), PIP4K2B (Affinity Capture-MS), PIP4K2B (Affinity Capture-MS), PIP4K2B (Affinity Capture-MS), PIP4K2B (Co-fractionation), PIP4K2B (Co-fractionation), PIP4K2B (Co-fractionation), SKP1 (Co-fractionation), PIP4K2B (Affinity Capture-MS), PIP4K2B (Biochemical Activity), PIP4K2B (Proximity Label-MS), PIP4K2B (Affinity Capture-MS), PIP4K2B (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

1 interactions.

A	Effect	B	Mechanism
MAPK14	down-regulates	PIP4K2B	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	29
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3779551	NM_003559.5(PIP4K2B):c.258-548_258-530del	Likely pathogenic

SpliceAI

2063 predictions. Top by Δscore:

Variant	Effect	Δscore
17:38770429:GACTC:G	donor_loss	1.0000
17:38770434:AC:A	donor_gain	1.0000
17:38770434:ACC:A	donor_gain	1.0000
17:38770435:C:CG	donor_loss	1.0000
17:38770435:CC:C	donor_gain	1.0000
17:38770435:CCC:C	donor_gain	1.0000
17:38770539:CCTG:C	acceptor_loss	1.0000
17:38770540:CTG:C	acceptor_loss	1.0000
17:38770541:T:A	acceptor_loss	1.0000
17:38771012:A:AC	donor_gain	1.0000
17:38771013:C:CC	donor_gain	1.0000
17:38771013:CTTT:C	donor_gain	1.0000
17:38771268:AAGAA:A	acceptor_gain	1.0000
17:38771269:AGAA:A	acceptor_gain	1.0000
17:38771270:GAA:G	acceptor_gain	1.0000
17:38771271:AA:A	acceptor_gain	1.0000
17:38771273:C:CC	acceptor_gain	1.0000
17:38771283:C:CT	acceptor_gain	1.0000
17:38771284:A:T	acceptor_gain	1.0000
17:38771288:A:C	acceptor_gain	1.0000
17:38777683:GTA:G	donor_loss	1.0000
17:38777685:A:AT	donor_loss	1.0000
17:38777686:C:A	donor_loss	1.0000
17:38777694:T:TA	donor_gain	1.0000
17:38779378:TTTA:T	donor_loss	1.0000
17:38779379:TTAC:T	donor_loss	1.0000
17:38779381:ACCT:A	donor_loss	1.0000
17:38779382:CCTT:C	donor_loss	1.0000
17:38779394:A:AC	donor_gain	1.0000
17:38779395:C:CC	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000012019 (17:38798098 C>T), RS1000116442 (17:38776095 C>T), RS1000219380 (17:38771487 C>A), RS1000272441 (17:38769536 C>G), RS1000296123 (17:38771783 C>A), RS1000397819 (17:38775800 G>A), RS1000556549 (17:38789339 T>C), RS1000611018 (17:38782972 G>A,T), RS1000697667 (17:38795981 T>C), RS1000708368 (17:38795666 G>A), RS1000749480 (17:38788067 T>C), RS1000847689 (17:38777260 T>C), RS1001018045 (17:38799244 G>A), RS1001072020 (17:38799054 G>A), RS1001232705 (17:38773007 C>G,T)

Disease associations

OMIM: gene MIM:603261 | disease phenotypes: MIM:162830, MIM:617014

GenCC curated gene-disease

Mondo (2): hereditary neutrophilia (MONDO:0008092), autosomal recessive severe congenital neutropenia due to CSF3R deficiency (MONDO:0014865)

Orphanet (2): Hereditary neutrophilia (Orphanet:279943), Autosomal recessive severe congenital neutropenia due to CSF3R deficiency (Orphanet:420702)

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000817_127	Height	3.000000e-10
GCST008163_338	Height	1.000000e-08
GCST008839_98	Height	4.000000e-17
GCST90000025_583	Appendicular lean mass	1.000000e-39

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004980	appendicular lean mass

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563010	Neutrophilia, Hereditary (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5667 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 118,223 (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
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL2104863	IMANIXIL	2	1,142
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL607707	PELITINIB	2	6,340
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol phosphate kinases

Binding affinities (BindingDB)

9 measured of 9 human assays (9 total across all organisms); most potent 9 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

46 potent at pChembl≥5 of 72 total, top 35 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.77	Kd	17	nM	NINTEDANIB
7.75	Kd	18	nM	LESTAURTINIB
7.52	IC50	30	nM	CHEMBL5271804
7.41	Kd	39	nM	SUNITINIB
7.11	Kd	77	nM	STAUROSPORINE
7.03	Kd	94	nM	KW-2449
6.85	Kd	140	nM	TOZASERTIB
6.80	Kd	160	nM	FEDRATINIB
6.58	Kd	260	nM	DOVITINIB
6.58	Kd	260	nM	SU-014813
6.57	Kd	270	nM	MIDOSTAURIN
6.08	Kd	830	nM	RUBOXISTAURIN
5.92	Kd	1200	nM	R-406
5.89	Kd	1300	nM	JNJ-7706621
5.80	Kd	1600	nM	PHA-665752
5.77	IC50	1700	nM	CHEMBL4436648
5.77	Kd	1700	nM	CHEMBL379218
5.72	IC50	1900	nM	CHEMBL4447308
5.68	IC50	2100	nM	IMANIXIL
5.58	Kd	2600	nM	PELITINIB
5.57	IC50	2700	nM	CHEMBL4454033
5.50	Kd	3200	nM	CGP-52421
5.43	Kd	3700	nM	CHEMBL1908395
5.42	IC50	3800	nM	IMANIXIL
5.37	IC50	4300	nM	CHEMBL4519752
5.35	Kd	4500	nM	GSK-461364
5.23	IC50	5900	nM	CHEMBL4446338
5.21	IC50	6200	nM	CHEMBL4461694
5.20	IC50	6300	nM	CHEMBL4472811
5.11	Kd	7800	nM	TG100-115
5.07	IC50	8600	nM	CHEMBL4577337
5.05	IC50	8900	nM	CHEMBL4533123
5.03	IC50	9400	nM	CHEMBL4455633
5.00	IC50	1.01e+04	nM	CHEMBL4449493
5.00	IC50	9900	nM	CHEMBL4439287

PubChem BioAssay actives

45 with measured affinity, of 331 total; 33 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
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624915: Binding constant for PIP5K2B kinase domain	kd	0.0170	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508033: Binding affinity to PIP5K2B	kd	0.0180	uM
(7R)-8-cyclopentyl-7-(cyclopentylmethyl)-2-(3,5-dichloro-4-hydroxyanilino)-5-methyl-7H-pteridin-6-one	1956671: Inhibition of PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of [33P]gamma-ATP and ATP by fluorescence based analysis	ic50	0.0300	uM
Sunitinib	435828: Binding constant for full-length PIP5K2B	kd	0.0390	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	435828: Binding constant for full-length PIP5K2B	kd	0.0770	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624915: Binding constant for PIP5K2B kinase domain	kd	0.0940	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435828: Binding constant for full-length PIP5K2B	kd	0.1400	uM
Fedratinib	624915: Binding constant for PIP5K2B kinase domain	kd	0.1600	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	435828: Binding constant for full-length PIP5K2B	kd	0.2600	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435828: Binding constant for full-length PIP5K2B	kd	0.2600	uM
Midostaurin	435828: Binding constant for full-length PIP5K2B	kd	0.2700	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	435828: Binding constant for full-length PIP5K2B	kd	0.8300	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	624915: Binding constant for PIP5K2B kinase domain	kd	1.2000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435828: Binding constant for full-length PIP5K2B	kd	1.3000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624915: Binding constant for PIP5K2B kinase domain	kd	1.6000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624915: Binding constant for PIP5K2B kinase domain	kd	1.7000	uM
N-[4-[5-[(Z)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]phenyl]methanesulfonamide	1607145: Inhibition of GST-tagged recombinant PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay	ic50	1.7000	uM
N-[4-[5-[(Z)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]phenyl]methanesulfonamide	1607145: Inhibition of GST-tagged recombinant PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay	ic50	1.9000	uM
4-amino-2-(4,4-dimethyl-2-oxoimidazolidin-1-yl)-N-[3-(trifluoromethyl)phenyl]pyrimidine-5-carboxamide	1956672: Inhibition of human full length PI5P4Kbeta expressed in Escherichia coli BL21(DE3) pre-incubated for 15 mins followed by ATP addition measured after 1 hr by TR-FRET assay	ic50	2.1000	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	435828: Binding constant for full-length PIP5K2B	kd	2.6000	uM
N-[4-[2-amino-5-[(Z)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]phenyl]methanesulfonamide	1607145: Inhibition of GST-tagged recombinant PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay	ic50	2.7000	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-N-methylbenzamide	508033: Binding affinity to PIP5K2B	kd	3.2000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624915: Binding constant for PIP5K2B kinase domain	kd	3.7000	uM
4-[5-[(Z)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]-N-methylbenzenesulfonamide	1607145: Inhibition of GST-tagged recombinant PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay	ic50	4.3000	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	624915: Binding constant for PIP5K2B kinase domain	kd	4.5000	uM
4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[6-(1H-indol-3-yl)pyrimidin-4-yl]amino]phenyl]benzamide	1547839: Inhibition of PI5P4Kbeta (unknown origin) incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	5.9000	uM
4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[6-(4-methylanilino)pyrimidin-4-yl]amino]phenyl]benzamide	1547839: Inhibition of PI5P4Kbeta (unknown origin) incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	6.2000	uM
4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[6-(4-phenylanilino)pyrimidin-4-yl]amino]phenyl]benzamide	1547839: Inhibition of PI5P4Kbeta (unknown origin) incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	6.3000	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	624915: Binding constant for PIP5K2B kinase domain	kd	7.8000	uM
1-[4-[5-[(Z)-(2-imino-4-oxo-1,3-thiazolidin-5-ylidene)methyl]-3-pyridinyl]phenyl]-3-methylurea	1607145: Inhibition of GST-tagged recombinant PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay	ic50	8.6000	uM
3-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[6-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrimidin-4-yl]amino]phenyl]benzamide	1547839: Inhibition of PI5P4Kbeta (unknown origin) incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	8.9000	uM
N-[4-[5-(1H-indol-4-yl)-3-pyridinyl]phenyl]methanesulfonamide	1607145: Inhibition of GST-tagged recombinant PI5P4Kbeta (unknown origin) incubated for 1 hr in presence of DPPS and PI5P by ADP-Glo assay	ic50	9.4000	uM
4-[[(E)-4-(dimethylamino)but-2-enoyl]amino]-N-[3-[[7-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-4-yl]amino]phenyl]benzamide	1547839: Inhibition of PI5P4Kbeta (unknown origin) incubated for 15 mins in presence of ATP by ADP-Glo assay	ic50	9.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression	3
Benzo(a)pyrene	affects methylation, decreases expression	2
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases expression	1
arsenite	increases methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
entinostat	decreases expression	1
fenpyroximate	decreases expression	1
4-chloro-N-((4-(1,1-dimethylethyl)phenyl)methyl)-3-ethyl-1-methyl-1H-pyrazole-5-carboxamide	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
torcetrapib	increases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
bisphenol S	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	decreases expression	1
Antimycin A	decreases expression	1
Caffeine	increases phosphorylation	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1

ChEMBL screening assays

124 unique, capped per target: 124 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017905	Binding	Inhibition of PIP5K2B assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_D7XI	Ubigene A-549 PIP4K2B KO	Cancer cell line	Male
CVCL_D8SZ	Ubigene HCT 116 PIP4K2B KO	Cancer cell line	Male
CVCL_D9NG	Ubigene HEK293 PIP4K2B KO	Transformed cell line	Female
CVCL_E0KT	Ubigene HeLa PIP4K2B KO	Cancer cell line	Female
CVCL_E1M2	HyCyte MCF-7 KO-hPIP4K2B	Cancer cell line	Female
CVCL_TD89	HAP1 PIP4K2B (-) 1	Cancer cell line	Male
CVCL_TD90	HAP1 PIP4K2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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