PIP5K1A

Summary

PIP5K1A (phosphatidylinositol-4-phosphate 5-kinase type 1 alpha, HGNC:8994) is a protein-coding gene on chromosome 1q21.3, encoding Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha (Q99755). Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cyto…. It is a selective cancer dependency (DepMap: 43.4% of cell lines).

Enables 1-phosphatidylinositol-4-phosphate 5-kinase activity and kinase binding activity. Involved in several processes, including activation of GTPase activity; focal adhesion assembly; and ruffle assembly. Located in several cellular components, including lamellipodium; nucleus; and ruffle membrane.

Source: NCBI Gene 8394 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 38 total — 1 likely-pathogenic
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 43.4% of screened cell lines
• MANE Select transcript: NM_001135638

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8994
Approved symbol	PIP5K1A
Name	phosphatidylinositol-4-phosphate 5-kinase type 1 alpha
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000143398
Ensembl biotype	protein_coding
OMIM	603275
Entrez	8394

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 34 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000349792, ENST00000368888, ENST00000368890, ENST00000409426, ENST00000418435, ENST00000424999, ENST00000441902, ENST00000447555, ENST00000454769, ENST00000460157, ENST00000461816, ENST00000464105, ENST00000468772, ENST00000481713, ENST00000486048, ENST00000486866, ENST00000489625, ENST00000908494, ENST00000908495, ENST00000908496, ENST00000908497, ENST00000908498, ENST00000908499, ENST00000908500, ENST00000908501, ENST00000908502, ENST00000908503, ENST00000908504, ENST00000908505, ENST00000908506, ENST00000927434, ENST00000927435, ENST00000927436, ENST00000927437, ENST00000927438, ENST00000927439, ENST00000927440, ENST00000927441, ENST00000927442, ENST00000927443, ENST00000927444, ENST00000927445, ENST00000927446

RefSeq mRNA: 5 — MANE Select: NM_001135638 NM_001135636, NM_001135637, NM_001135638, NM_001330689, NM_003557

CCDS: CCDS44219, CCDS44220, CCDS44221, CCDS81374, CCDS990

Canonical transcript exons

ENST00000368888 — 16 exons

Exon	Start	End
ENSE00001585358	151198552	151199081
ENSE00001661211	151242123	151242269
ENSE00001706890	151236558	151236763
ENSE00001785375	151239955	151240039
ENSE00001826563	151247863	151249531
ENSE00003469152	151246920	151246965
ENSE00003477590	151234197	151234496
ENSE00003519433	151232248	151232365
ENSE00003558757	151238182	151238265
ENSE00003571154	151242438	151242567
ENSE00003602128	151227320	151227400
ENSE00003603586	151224371	151224406
ENSE00003618431	151239130	151239178
ENSE00003653780	151224245	151224279
ENSE00003665093	151232551	151232703
ENSE00003789778	151231671	151231801

Expression profiles

Bgee: expression breadth ubiquitous, 274 present calls, max score 94.92.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.7526 / max 403.4021, expressed in 1812 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5215	36.7526	1812

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	94.92	gold quality
colonic epithelium	UBERON:0000397	94.81	gold quality
adrenal tissue	UBERON:0018303	94.60	gold quality
left testis	UBERON:0004533	94.37	gold quality
sural nerve	UBERON:0015488	93.37	gold quality
calcaneal tendon	UBERON:0003701	93.23	gold quality
mucosa of stomach	UBERON:0001199	93.20	gold quality
skin of leg	UBERON:0001511	93.02	gold quality
testis	UBERON:0000473	92.96	gold quality
left uterine tube	UBERON:0001303	92.88	gold quality
skin of abdomen	UBERON:0001416	92.79	gold quality
islet of Langerhans	UBERON:0000006	92.52	gold quality
endocervix	UBERON:0000458	92.49	gold quality
ectocervix	UBERON:0012249	92.47	gold quality
gall bladder	UBERON:0002110	92.14	gold quality
adenohypophysis	UBERON:0002196	92.09	gold quality
left lobe of thyroid gland	UBERON:0001120	92.08	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.06	gold quality
upper lobe of left lung	UBERON:0008952	91.98	gold quality
ventricular zone	UBERON:0003053	91.96	gold quality
right lobe of thyroid gland	UBERON:0001119	91.79	gold quality
right lung	UBERON:0002167	91.76	gold quality
left ovary	UBERON:0002119	91.74	gold quality
ganglionic eminence	UBERON:0004023	91.74	gold quality
body of uterus	UBERON:0009853	91.59	gold quality
lower esophagus muscularis layer	UBERON:0035833	91.59	gold quality
metanephros cortex	UBERON:0010533	91.58	gold quality
lower esophagus	UBERON:0013473	91.57	gold quality
thyroid gland	UBERON:0002046	91.49	gold quality
muscle of leg	UBERON:0001383	91.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.56

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

99 targeting PIP5K1A, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4713-3P	100.00	65.92	505
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-765	99.84	68.24	2442

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 43.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 26)

• Membrane ruffling requires coordination between this enzyme and Rac signaling. (PMID:12682053)
• in addition to its effects upon Rac activity, Ajuba can also influence cell migration through regulation of PI(4,5)P2 synthesis through direct activation of PIPKIalpha enzyme activity (PMID:15870270)
• identified apoptotic stimuli that initiate a signaling pathway during cell death that leads to caspase-independent downregulation of PIP5Kalpha. (PMID:16979564)
• Type I phosphatidylinositol-4-phosphate-5-kinase (PI5KI) alpha and gamma isoforms were identified as the enzymes responsible for PIP2 synthesis in natural killer cells. (PMID:18073347)
• beta-arrestins direct the localization of PIP5K Ialpha and PIP(2) production to agonist-activated 7TMRs, thereby regulating receptor internalization (PMID:18534983)
• PI4P5-K Ialpha-mediated PIP(2) production is crucial for HIV-1 entry and the early steps of infection in permissive lymphocytes. (PMID:18981107)
• Extracellular calcium (Cao) stimulated PIP5K1alpha recruitment to the E-cadherin-catenin complex in the plasma membrane. (PMID:19158393)
• The data suggest that activation of FcgammaRIIA leads to membrane rafts coalescing into signaling platforms containing PIP5-kinase Ialpha and PI(4,5)P(2). (PMID:19331818)
• Localized production of Phosphatidylinositol 4,5-bisphosphate by PIP5K1A is required for invadopodia formation by breast cancer cells. (PMID:20426790)
• Results define the role of PIPKI-alpha in cell migration and describes a new mechanism for the spatial regulation of Rac1 activity that is critical for cell migration. (PMID:20660631)
• CD28 regulates phosphatidylinositol 4,5-biphosphate turnover by recruiting and activating phosphatidylinositol 4-phosphate 5-kinases alpha in human primary CD4(+) T lymphocytes. (PMID:23589613)
• PIP5K1A is modified by polySUMO-2 only during apoptosis. (PMID:23994136)
• PIP5K1A modulates ribosomal RNA gene silencing through its interaction with histone H3 lysine 9 trimethylation and heterochromatin protein HP1-alpha. (PMID:26157143)
• These results indicate that PP1 is recruited to the extracellular calcium-dependent E-cadherin-catenin-PIP5K1a complex in the plasma membrane to activate PIP5K1a, which is required for PLC-g1 activation leading to keratinocyte differentiation. (PMID:27340655)
• Blockade of IQGAP1 interaction with PIPKIalpha or PI(3)K inhibited PtdIns(3,4,5)P3 generation and signalling, and selectively diminished cancer cell survival. (PMID:27870828)
• The results suggest that PIP5KA is a novel degradative substrate of NEDD4 and that the PIP5KA-dependent phosphatidylinositol 4,5-diphosphate pool contributing to breast cancer cell proliferation through PI3K/Akt activation is negatively controlled by NEDD4. (PMID:29851245)
• PIP5K1alpha was associated with poor patient outcome in triple-negative BC. It increased expression of pSer-473 AKT and invasiveness of triple-negative MDA-MB-231 cells. Inhibition reduced expression of pSer-473 AKT and its downstream effectors in xenograft tumors. In ER(+) cancer cells, PIP5K1alpha acted on pSer-473 AKT, and was in complexes with VEGFR2, serving as co-factor of ER-alpha to regulate activities of targe… (PMID:30104711)
• KRAS-specific interactor that mediates oncogenic KRAS signaling and proliferation (PMID:30194290)
• Type I Phosphatidylinositol-4-Phosphate 5-Kinases alpha and gamma Play a Key Role in Targeting HIV-1 Pr55(Gag) to the Plasma Membrane. (PMID:32376619)
• Phosphatidylinositol-4-phosphate 5-kinase type 1alpha attenuates Abeta production by promoting non-amyloidogenic processing of amyloid precursor protein. (PMID:32686865)
• CLIC1 recruits PIP5K1A/C to induce cell-matrix adhesions for tumor metastasis. (PMID:33079727)
• Cross-species identification of PIP5K1-, splicing- and ubiquitin-related pathways as potential targets for RB1-deficient cells. (PMID:33591981)
• Circ_PIP5K1A regulates cisplatin resistance and malignant progression in non-small cell lung cancer cells and xenograft murine model via depending on miR-493-5p/ROCK1 axis. (PMID:34537072)
• FcgammaRIIIa receptor interacts with androgen receptor and PIP5K1alpha to promote growth and metastasis of prostate cancer. (PMID:34932854)
• Lipid kinase PIP5K1A regulates let-7 microRNA biogenesis through interacting with nuclear export protein XPO5. (PMID:37655623)
• Human IL-17A protein production is controlled through a PIP5K1alpha-dependent translational checkpoint. (PMID:37874883)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pip5k1ab	ENSDARG00000024642
mus_musculus	Pip5k1a	ENSMUSG00000028126
rattus_norvegicus	Pip5k1a	ENSRNOG00000021068
drosophila_melanogaster	sktl	FBGN0016984
drosophila_melanogaster	PIP5K59B	FBGN0034789
caenorhabditis_elegans	ppk-1	WBGENE00004087

Paralogs (6): PIP5K1B (ENSG00000107242), PIP4K2A (ENSG00000150867), PIP4K2C (ENSG00000166908), PIP5KL1 (ENSG00000167103), PIP5K1C (ENSG00000186111), PIP4K2B (ENSG00000276293)

Protein

Protein identifiers

Phosphatidylinositol 4-phosphate 5-kinase type-1 alpha — Q99755 (reviewed: Q99755)

Alternative names: 68 kDa type I phosphatidylinositol 4-phosphate 5-kinase alpha, Phosphatidylinositol 4-phosphate 5-kinase type I alpha

All UniProt accessions (6): Q99755, A2A5X0, A6PW56, A6PW57, A6PW58, E9PSF8

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility. PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3). PIP5K1A-mediated phosphorylation of PtdIns(4)P is the predominant pathway for PtdIns(4,5)P2 synthesis. Can also use phosphatidylinositol (PtdIns) as substrate in vitro. Together with PIP5K1C, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps. Promotes particle ingestion by activating the WAS GTPase-binding protein that induces Arp2/3 dependent actin polymerization at the nascent phagocytic cup. Together with PIP5K1B, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion. Recruited to the plasma membrane by the E-cadherin/beta-catenin complex where it provides the substrate PtdIns(4,5)P2 for the production of PtdIns(3,4,5)P3, IP3 and DAG, that will mobilize internal calcium and drive keratinocyte differentiation. Positively regulates insulin-induced translocation of SLC2A4 to the cell membrane in adipocytes. Together with PIP5K1C has a role during embryogenesis. Independently of its catalytic activity, is required for membrane ruffling formation, actin organization and focal adhesion formation during directional cell migration by controlling integrin-induced translocation of the small GTPase RAC1 to the plasma membrane. Also functions in the nucleus where it acts as an activator of TUT1 adenylyltransferase activity in nuclear speckles, thereby regulating mRNA polyadenylation of a select set of mRNAs.

Subunit / interactions. Interacts with RAC1. Interacts with TUT1. Forms a complex with CDH1/E-cadherin, CTNNB1/beta-catenin and CTNND1 at the plasma membrane upon calcium stimulation. Found in a ternary complex with IRS1 and DGKZ in the absence of insulin stimulation. Interacts with DGKZ. Interacts with PIP4K2C; the interaction inhibits PIP5K1A kinase activity.

Subcellular location. Cell membrane. Cytoplasm. Nucleus. Nucleus speckle. Cell projection. Ruffle. Lamellipodium.

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

Activity regulation. Activated by diarachidonoyl phosphatidic acid (DAPA), when 1,2-dipalmitoyl-PI4P is used as a substrate.

Isoforms (4)

UniProt ID	Names	Canonical?
Q99755-1	1, PIP5KIalpha2	yes
Q99755-2	2, PIP5KIalpha3
Q99755-3	3, PIP5KIalpha1
Q99755-4	4

RefSeq proteins (5): NP_001129108, NP_001129109, NP_001129110, NP_001317618, NP_003548 (=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 2.7.1.68 — 1-phosphatidylinositol-4-phosphate 5-kinase (BRENDA: 15 organisms, 50 substrates, 41 inhibitors, 41 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4-PHOSPHATE	0.0012–4.1	14
ATP	0.002–0.2	13
1-STEAROYL-2-ARACHIDONOYL PHOSPHATIDYL-1D-MYO-IN	4.9–16	3
1-STEAROYL-2-OLEOYL PHOSPHATIDYL-1D-MYO-INOSITOL	1.6–3.7	3
1-PHOSPHATIDYL-1D-MYO-INOSITOL 3-PHOSPHATE	0.005–0.065	2
PHOSPHATIDYLINOSITOL 3,4-BISPHOSPHATE	0.006–0.08	2
GTP	0.133	1
PHOSPHATIDYLINOSITOL 3-PHOSPHATE	0.12	1

Catalyzed reactions (Rhea), 8 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H(+) (RHEA:14425)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ADP + H(+) (RHEA:40363)
• 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ADP + H(+) (RHEA:40367)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40375)
• 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40379)
• 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol + ATP = 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40383)
• 1,2-di-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol + ATP = 1,2-di(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40387)
• 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4-phosphate) + ATP = 1,2-dihexadecanoyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H(+) (RHEA:65356)

UniProt features (15 total): mutagenesis site 5, splice variant 4, chain 1, domain 1, sequence conflict 1, region of interest 1, modified residue 1, cross-link 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99755-F1	70.92	0.48

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 (2): 486, 103

Mutagenesis-validated functional residues (5):

Position	Phenotype
223	decreased 1-phosphatidylinositol-4-phosphate 5-kinase activity with 1-octadecanoyl-2-(5z,8z,11z,14z)-eicosatetraenoyl-sn
322	increased enzyme activation by diarachidonoyl phosphatidic acid (dapa).
322	does not affect targeting of rac1 to the plasma membrane; when associated with q-440.
440	does not affect targeting of rac1 to the plasma membrane; when associated with n-322.
215	decreased 1-phosphatidylinositol-4-phosphate 5-kinase activity with 1-octadecanoyl-2-(5z,8z,11z,14z)-eicosatetraenoyl-sn

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 248 (showing top): BIOCARTA_RHO_PATHWAY, MODULE_97, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_CELL_CHEMOTAXIS, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_FOCAL_ADHESION_ASSEMBLY, MAZ_Q6, GOBP_REGULATION_OF_GTPASE_ACTIVITY, MODULE_182, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE

GO Biological Process (18): glycerophospholipid metabolic process (GO:0006650), phosphatidylinositol biosynthetic process (GO:0006661), phagocytosis (GO:0006909), signal transduction (GO:0007165), phospholipid biosynthetic process (GO:0008654), fibroblast migration (GO:0010761), cell migration (GO:0016477), actin cytoskeleton organization (GO:0030036), keratinocyte differentiation (GO:0030216), phosphatidylinositol phosphate biosynthetic process (GO:0046854), focal adhesion assembly (GO:0048041), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), cell chemotaxis (GO:0060326), protein localization to plasma membrane (GO:0072659), activation of GTPase activity (GO:0090630), ruffle assembly (GO:0097178), lipid metabolic process (GO:0006629), phosphatidylinositol metabolic process (GO:0046488)

GO Molecular Function (10): 1-phosphatidylinositol-3-phosphate 5-kinase activity (GO:0000285), ATP binding (GO:0005524), 1-phosphatidylinositol-4-phosphate 5-kinase activity (GO:0016308), kinase binding (GO:0019900), phosphatidylinositol kinase activity (GO:0052742), 1-phosphatidylinositol-5-kinase activity (GO:0052810), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (13): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), nuclear speck (GO:0016607), lamellipodium (GO:0030027), ruffle membrane (GO:0032587), ruffle (GO:0001726), cytoplasm (GO:0005737), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
PI Metabolism	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	5
phosphatidylinositol kinase activity	3
phospholipid metabolic process	2
cell leading edge	2
plasma membrane bounded cell projection	2
glycerolipid metabolic process	1
biosynthetic process	1
phosphatidylinositol metabolic process	1
endocytosis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
lipid biosynthetic process	1
organophosphate biosynthetic process	1
ameboidal-type cell migration	1
cell motility	1
cytoskeleton organization	1
actin filament-based process	1
epidermal cell differentiation	1
skin development	1
glycerophospholipid biosynthetic process	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
protein localization to membrane	1
protein localization to cell periphery	1
positive regulation of GTPase activity	1
ruffle organization	1
plasma membrane bounded cell projection assembly	1
primary metabolic process	1
phosphorus metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
enzyme binding	1

Protein interactions and networks

STRING

1490 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIP5K1A	AP2M1	P20172	711
PIP5K1A	ARF6	P26438	614
PIP5K1A	PI4K2A	Q9BTU6	605
PIP5K1A	TUT1	Q9H6E5	595
PIP5K1A	PIKFYVE	Q9Y2I7	549
PIP5K1A	PI4KB	P78405	540
PIP5K1A	PAPOLG	Q9BWT3	513
PIP5K1A	PIP5KL1	Q5T9C9	499
PIP5K1A	KRAS	P01116	497
PIP5K1A	PSMD4	P55036	494
PIP5K1A	PI4KA	P42356	489
PIP5K1A	ARRB2	P32121	489
PIP5K1A	CDH1	P12830	466
PIP5K1A	IPMK	Q8NFU5	453
PIP5K1A	PAPOLA	P51003	452

IntAct

117 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
KBTBD7	METTL15	psi-mi:“MI:0914”(association)	0.730
CCDC97	SF3B1	psi-mi:“MI:0914”(association)	0.730
FRYL	YWHAZ	psi-mi:“MI:0914”(association)	0.710
PIP5K1A	KRAS	psi-mi:“MI:0915”(physical association)	0.660
PIP5K1A	KRAS	psi-mi:“MI:0407”(direct interaction)	0.660
GPR156	PLD2	psi-mi:“MI:0914”(association)	0.640
KANK4	TRAPPC3	psi-mi:“MI:0914”(association)	0.640
TUT1	PIP5K1A	psi-mi:“MI:0915”(physical association)	0.560
TUT1	PIP5K1A	psi-mi:“MI:0914”(association)	0.560
TUT1	CSTF2	psi-mi:“MI:0914”(association)	0.530
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
KCTD17	CBX4	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530
KLHDC3	DPYSL4	psi-mi:“MI:0914”(association)	0.530
HEATR3	SLC27A2	psi-mi:“MI:0914”(association)	0.530
IMPDH1	BCAT2	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
PFDN2	CDC40	psi-mi:“MI:0914”(association)	0.530
PRKCA	DUSP11	psi-mi:“MI:0914”(association)	0.530

BioGRID (204): PIP5K1A (Affinity Capture-RNA), PIP5K1A (Affinity Capture-RNA), PIP5K1A (Affinity Capture-MS), PIP5K1A (Affinity Capture-MS), PIP5K1A (Affinity Capture-MS), PIP5K1A (Affinity Capture-MS), FLNC (Affinity Capture-MS), PIP5K1C (Affinity Capture-MS), DCAF5 (Affinity Capture-MS), NRP1 (Affinity Capture-MS), RAD21 (Affinity Capture-MS), CENPB (Affinity Capture-MS), NRXN3 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), HTATSF1 (Affinity Capture-MS)

ESM2 similar proteins: A0A096MJN4, A2A3N6, A3KMI0, A6H8H2, B7ZC32, D3ZSI8, F1M4A4, F4IJV4, O14986, O43236, O48709, O73630, O80452, P08487, P10686, P19174, P19838, P23678, P25799, P33173, P41230, P70181, P70182, Q04861, Q12756, Q17BU3, Q3B8D5, Q5CZZ9, Q5VZ89, Q5XUN4, Q5ZJ58, Q62077, Q63369, Q6F3J0, Q6P3S1, Q6P5D3, Q7PHR1, Q7YTB0, Q7Z401, Q80UP5

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

3 interactions.

A	Effect	B	Mechanism
“phosphatidic acid”	up-regulates	PIP5K1A	“chemical activation”
DVL3	up-regulates	PIP5K1A	binding
PIP5K1A	up-regulates	LRP6

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 156 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Ras activation upon Ca2+ influx through NMDA receptor	5	27.2×	1e-04
VEGFR2 mediated cell proliferation	5	27.2×	1e-04
RAF activation	6	19.2×	1e-04
Signaling by RAF1 mutants	6	15.9×	2e-04
Signaling by moderate kinase activity BRAF mutants	6	14.5×	2e-04
Paradoxical activation of RAF signaling by kinase inactive BRAF	6	14.5×	2e-04
Signaling downstream of RAS mutants	6	14.5×	2e-04
Signaling by BRAF and RAF1 fusions	7	11.4×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
Ras protein signal transduction	7	10.0×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3064175	NM_001135638.2(PIP5K1A):c.1114C>T (p.Arg372Ter)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3656 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:151231699:T:A	I89N	1.000
1:151231707:G:C	G92R	1.000
1:151231708:G:A	G92D	1.000
1:151231708:G:T	G92V	1.000
1:151231711:T:A	I93N	1.000
1:151231711:T:G	I93S	1.000
1:151231749:C:A	R106S	1.000
1:151231750:G:C	R106P	1.000
1:151231752:G:C	D107H	1.000
1:151231752:G:T	D107Y	1.000
1:151231753:A:C	D107A	1.000
1:151231753:A:G	D107G	1.000
1:151231753:A:T	D107V	1.000
1:151231756:T:A	V108D	1.000
1:151231759:T:A	L109H	1.000
1:151231759:T:C	L109P	1.000
1:151231767:G:C	D112H	1.000
1:151231767:G:T	D112Y	1.000
1:151231768:A:C	D112A	1.000
1:151231768:A:G	D112G	1.000
1:151231768:A:T	D112V	1.000
1:151231770:T:C	F113L	1.000
1:151231771:T:C	F113S	1.000
1:151231771:T:G	F113C	1.000
1:151231772:C:A	F113L	1.000
1:151231772:C:G	F113L	1.000
1:151231795:T:C	F121S	1.000
1:151232252:G:A	G125R	1.000
1:151232252:G:C	G125R	1.000
1:151232252:G:T	G125W	1.000

dbSNP variants (sampled 300 via entrez): RS1000200659 (1:151249500 T>G), RS1000216773 (1:151231411 C>A,T), RS1000253140 (1:151237439 T>A), RS1000259226 (1:151207694 G>T), RS1000271599 (1:151223833 A>G), RS1000330919 (1:151243623 G>C), RS1000407107 (1:151217401 C>A,G,T), RS1000445836 (1:151196186 C>G,T), RS1000466890 (1:151243288 G>A), RS1000510774 (1:151219645 G>A), RS1000540964 (1:151237945 T>G), RS1000622347 (1:151201871 A>G), RS1000685488 (1:151208080 G>A,C), RS1000698433 (1:151249216 A>G), RS1000736411 (1:151201545 G>A)

Disease associations

OMIM: gene MIM:603275 | disease phenotypes: MIM:618587

GenCC curated gene-disease

Mondo (1): intellectual developmental disorder 60 with seizures (MONDO:0032823)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_38	Body mass index	4.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5969 (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: 137,399 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL572878	TOZASERTIB	2	2,998
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)

8 measured of 8 human assays (8 total across all organisms); most potent 8 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
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

44 potent at pChembl≥5 of 46 total, top 33 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.96	IC50	11	nM	CHEMBL5191668
7.44	Kd	36	nM	LESTAURTINIB
7.37	Kd	43	nM	STAUROSPORINE
7.31	Kd	49	nM	NINTEDANIB
7.29	Kd	51	nM	KW-2449
7.24	IC50	58	nM	CHEMBL5206569
7.18	Kd	66	nM	FEDRATINIB
7.02	IC50	95	nM	CHEMBL5171272
6.89	Kd	130	nM	SU-014813
6.89	Kd	130	nM	TOZASERTIB
6.60	Kd	250	nM	CHEMBL379218
6.55	Kd	280	nM	PHA-665752
6.51	Kd	310	nM	MIDOSTAURIN
6.34	IC50	460	nM	CHEMBL5591914
6.23	Kd	590	nM	CHEMBL1908395
6.16	Kd	690	nM	RUBOXISTAURIN
6.11	Kd	770	nM	GSK-461364
6.10	IC50	790	nM	CHEMBL5591586
6.00	IC50	1000	nM	CHEMBL203535
5.99	IC50	1020	nM	CHEMBL5595669
5.84	IC50	1440	nM	CHEMBL5564146
5.81	IC50	1550	nM	CHEMBL4284630
5.75	Kd	1800	nM	TG100-115
5.72	Kd	1900	nM	DOVITINIB
5.72	Kd	1900	nM	R-406
5.50	Kd	3200	nM	CRIZOTINIB
5.48	Kd	3300	nM	BOSUTINIB
5.44	IC50	3650	nM	CHEMBL5566640
5.31	IC50	4930	nM	CHEMBL3913746
5.31	Kd	4900	nM	CGP-52421
5.27	Kd	5400	nM	SUNITINIB
5.04	Kd	9200	nM	JNJ-7706621
5.01	Kd	9700	nM	TAE-684

PubChem BioAssay actives

43 with measured affinity, of 242 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
N-[4-(3-acetamido-5-anilinophenyl)-2-pyridinyl]oxane-4-carboxamide	1888783: Inhibition of PIP5Kalpha (unknown origin)	ic50	0.0110	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	508032: Binding affinity to PIP5K1A	kd	0.0360	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	435190: Binding constant for full-length PIP5K1A	kd	0.0430	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624824: Binding constant for PIP5K1A kinase domain	kd	0.0490	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624824: Binding constant for PIP5K1A kinase domain	kd	0.0510	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-(1,3-dioxolan-2-ylmethyl)-N-methylbenzamide	1888783: Inhibition of PIP5Kalpha (unknown origin)	ic50	0.0580	uM
Fedratinib	624824: Binding constant for PIP5K1A kinase domain	kd	0.0660	uM
N-[4-[3-anilino-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888783: Inhibition of PIP5Kalpha (unknown origin)	ic50	0.0950	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	435190: Binding constant for full-length PIP5K1A	kd	0.1300	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	435190: Binding constant for full-length PIP5K1A	kd	0.1300	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624824: Binding constant for PIP5K1A kinase domain	kd	0.2500	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	624824: Binding constant for PIP5K1A kinase domain	kd	0.2800	uM
Midostaurin	435190: Binding constant for full-length PIP5K1A	kd	0.3100	uM
4-[[(4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-yl]oxymethyl]-1-(3-nitrophenyl)triazole	2107943: Inhibition of recombinant human PIP5K1alpha expressed in Escherichia coli BL21 (DE3) using phosphatidylinositol-4-phosphate as substrate preincubated for 10 mins followed by substrate and ATP addition and further incubated under dark condition with constant shaking for 30 mins by capillary electrophoresis	ic50	0.4600	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624824: Binding constant for PIP5K1A kinase domain	kd	0.5900	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	435190: Binding constant for full-length PIP5K1A	kd	0.6900	uM
5-[6-[(4-methylpiperazin-1-yl)methyl]benzimidazol-1-yl]-3-[(1R)-1-[2-(trifluoromethyl)phenyl]ethoxy]thiophene-2-carboxamide	624824: Binding constant for PIP5K1A kinase domain	kd	0.7700	uM
4-[4-[[(4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-yl]oxymethyl]triazol-1-yl]benzaldehyde	2107943: Inhibition of recombinant human PIP5K1alpha expressed in Escherichia coli BL21 (DE3) using phosphatidylinositol-4-phosphate as substrate preincubated for 10 mins followed by substrate and ATP addition and further incubated under dark condition with constant shaking for 30 mins by capillary electrophoresis	ic50	0.7900	uM
N-[4-(2-anilino-4-pyridinyl)-2-pyridinyl]oxolane-3-carboxamide	1888783: Inhibition of PIP5Kalpha (unknown origin)	ic50	1.0000	uM
4-[[(4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-yl]oxymethyl]-1-phenyltriazole	2107943: Inhibition of recombinant human PIP5K1alpha expressed in Escherichia coli BL21 (DE3) using phosphatidylinositol-4-phosphate as substrate preincubated for 10 mins followed by substrate and ATP addition and further incubated under dark condition with constant shaking for 30 mins by capillary electrophoresis	ic50	1.0200	uM
4-[[(4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-yl]oxymethyl]-1-(4-methoxyphenyl)triazole	2107943: Inhibition of recombinant human PIP5K1alpha expressed in Escherichia coli BL21 (DE3) using phosphatidylinositol-4-phosphate as substrate preincubated for 10 mins followed by substrate and ATP addition and further incubated under dark condition with constant shaking for 30 mins by capillary electrophoresis	ic50	1.4400	uM
4-(2-amino-3-cyano-6-hydroxy-5,8-dioxo-7-undecyl-4H-chromen-4-yl)benzoic acid	2107943: Inhibition of recombinant human PIP5K1alpha expressed in Escherichia coli BL21 (DE3) using phosphatidylinositol-4-phosphate as substrate preincubated for 10 mins followed by substrate and ATP addition and further incubated under dark condition with constant shaking for 30 mins by capillary electrophoresis	ic50	1.5500	uM
3-[2,4-diamino-7-(3-hydroxyphenyl)pteridin-6-yl]phenol	624824: Binding constant for PIP5K1A kinase domain	kd	1.8000	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	624824: Binding constant for PIP5K1A kinase domain	kd	1.9000	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435190: Binding constant for full-length PIP5K1A	kd	1.9000	uM
Crizotinib	624824: Binding constant for PIP5K1A kinase domain	kd	3.2000	uM
Bosutinib	624824: Binding constant for PIP5K1A kinase domain	kd	3.3000	uM
6-[4-[[(4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexahydrophenanthren-2-yl]oxymethyl]triazol-1-yl]-2-[2-(dimethylamino)ethyl]-3a,4-dihydrobenzo[de]isoquinoline-1,3-dione	2107943: Inhibition of recombinant human PIP5K1alpha expressed in Escherichia coli BL21 (DE3) using phosphatidylinositol-4-phosphate as substrate preincubated for 10 mins followed by substrate and ATP addition and further incubated under dark condition with constant shaking for 30 mins by capillary electrophoresis	ic50	3.6500	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	508032: Binding affinity to PIP5K1A	kd	4.9000	uM
1-[[5-[2-[(2-chloro-4-pyridinyl)amino]pyrimidin-4-yl]-4-(cyclopropylmethyl)pyrimidin-2-yl]amino]-2-methylpropan-2-ol	2187644: Inhibition of human PIP5K1A using PI/PS as substrate by ADP-Glo assay	ic50	4.9300	uM
Sunitinib	435190: Binding constant for full-length PIP5K1A	kd	5.4000	uM
4-[[5-amino-1-(2,6-difluorobenzoyl)-1,2,4-triazol-3-yl]amino]benzenesulfonamide	435190: Binding constant for full-length PIP5K1A	kd	9.2000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624824: Binding constant for PIP5K1A kinase domain	kd	9.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	increases expression	2
Arsenic	increases abundance, increases expression, affects methylation, affects cotreatment	2
Estradiol	affects reaction, increases expression	2
FR900359	decreases phosphorylation	1
bisphenol A	increases expression, affects reaction	1
beta-lapachone	increases expression	1
sodium arsenite	increases expression, affects cotreatment, increases abundance	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
abrine	increases expression	1
jinfukang	decreases expression	1
Bortezomib	decreases expression	1
Amiodarone	increases expression	1
Vehicle Emissions	increases abundance, increases expression	1
Azacitidine	decreases expression	1
Benzo(a)pyrene	affects methylation, increases methylation	1
Caffeine	affects phosphorylation	1
Coumestrol	increases expression	1
Diethylstilbestrol	increases expression	1
Doxorubicin	decreases expression	1
Ketoconazole	increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Silicon Dioxide	increases expression	1
Silver	increases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	decreases expression	1
Cadmium Chloride	increases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

119 unique, capped per target: 119 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017904	Binding	Inhibition of PIP5K1A 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: 5 cancer cell line, 2 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3DX	Abcam HEK293T PIP5K1A KO	Transformed cell line	Female
CVCL_D7XK	Ubigene A-549 PIP5K1A KO	Cancer cell line	Male
CVCL_D8T1	Ubigene HCT 116 PIP5K1A KO	Cancer cell line	Male
CVCL_D9NI	Ubigene HEK293 PIP5K1A KO	Transformed cell line	Female
CVCL_E0KV	Ubigene HeLa PIP5K1A KO	Cancer cell line	Female
CVCL_TD92	HAP1 PIP5K1A (-) 1	Cancer cell line	Male
CVCL_TD93	HAP1 PIP5K1A (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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