PIP5K1C

Summary

PIP5K1C (phosphatidylinositol-4-phosphate 5-kinase type 1 gamma, HGNC:8996) is a protein-coding gene on chromosome 19p13.3, encoding Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (O60331). 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….

This locus encodes a type I phosphatidylinositol 4-phosphate 5-kinase. The encoded protein catalyzes phosphorylation of phosphatidylinositol 4-phosphate, producing phosphatidylinositol 4,5-bisphosphate. This enzyme is found at synapses and has been found to play roles in endocytosis and cell migration. Mutations at this locus have been associated with lethal congenital contractural syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.

Source: NCBI Gene 23396 — RefSeq curated summary.

At a glance

• Gene–disease (curated): PIP5K1C-related neurodevelopmental disorder (Strong, ClinGen) — +3 more curated relationships
• Clinical variants (ClinVar): 289 total — 6 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 6
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_012398

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8996
Approved symbol	PIP5K1C
Name	phosphatidylinositol-4-phosphate 5-kinase type 1 gamma
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PIP5Kgamma, KIAA0589, LCCS3
Ensembl gene	ENSG00000186111
Ensembl biotype	protein_coding
OMIM	606102
Entrez	23396

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 23 protein_coding, 4 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000335312, ENST00000537021, ENST00000539785, ENST00000587482, ENST00000589578, ENST00000592530, ENST00000636612, ENST00000637724, ENST00000679828, ENST00000679885, ENST00000876619, ENST00000876620, ENST00000876621, ENST00000876622, ENST00000876623, ENST00000876624, ENST00000876625, ENST00000876626, ENST00000876627, ENST00000876628, ENST00000876629, ENST00000876630, ENST00000918774, ENST00000918775, ENST00000918776, ENST00000967140, ENST00000967141, ENST00000967142

RefSeq mRNA: 3 — MANE Select: NM_012398 NM_001195733, NM_001300849, NM_012398

CCDS: CCDS32872, CCDS56074, CCDS74257

Canonical transcript exons

ENST00000335312 — 18 exons

Exon	Start	End
ENSE00000664358	3644087	3644251
ENSE00000664359	3643243	3643381
ENSE00000664360	3642907	3642939
ENSE00000664361	3641705	3641809
ENSE00000664362	3638884	3639016
ENSE00000664363	3633437	3633520
ENSE00001056314	3630183	3633169
ENSE00002751293	3700297	3700468
ENSE00003474081	3660966	3661083
ENSE00003547074	3651826	3652031
ENSE00003547932	3656405	3656557
ENSE00003562391	3647338	3647386
ENSE00003594660	3664822	3664914
ENSE00003630867	3661871	3662001
ENSE00003639966	3653290	3653589
ENSE00003651897	3645974	3646058
ENSE00003656395	3648625	3648708
ENSE00003662736	3667322	3667353

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 97.76.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 29.8567 / max 261.1234, expressed in 1814 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
178329	29.8567	1814

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	97.76	gold quality
cerebellar cortex	UBERON:0002129	97.45	gold quality
cerebellar hemisphere	UBERON:0002245	97.45	gold quality
decidua	UBERON:0002450	97.38	gold quality
Brodmann (1909) area 10	UBERON:0013541	97.29	gold quality
cerebellum	UBERON:0002037	97.19	gold quality
left testis	UBERON:0004533	96.77	gold quality
right testis	UBERON:0004534	96.51	gold quality
paraflocculus	UBERON:0005351	96.09	gold quality
right frontal lobe	UBERON:0002810	95.79	gold quality
cerebellar vermis	UBERON:0004720	95.23	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.07	gold quality
lower esophagus	UBERON:0013473	95.04	gold quality
middle temporal gyrus	UBERON:0002771	94.85	gold quality
testis	UBERON:0000473	94.58	gold quality
stromal cell of endometrium	CL:0002255	94.51	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.44	gold quality
CA1 field of hippocampus	UBERON:0003881	94.43	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.31	gold quality
frontal cortex	UBERON:0001870	94.28	gold quality
superior frontal gyrus	UBERON:0002661	94.18	gold quality
cingulate cortex	UBERON:0003027	94.14	gold quality
anterior cingulate cortex	UBERON:0009835	94.09	gold quality
neocortex	UBERON:0001950	93.99	gold quality
saphenous vein	UBERON:0007318	93.98	gold quality
prefrontal cortex	UBERON:0000451	93.92	gold quality
frontal pole	UBERON:0002795	93.86	gold quality
parietal lobe	UBERON:0001872	93.79	gold quality
Brodmann (1909) area 46	UBERON:0006483	93.74	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.68	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EZH2

miRNA regulators (miRDB)

128 targeting PIP5K1C, 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-4283	100.00	66.42	2097
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-6077	99.99	68.04	2299
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-25-3P	99.98	74.60	1817
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1273H-5P	99.77	66.32	2471

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• we show that the predominant brain splice variant of PtdInsPKI gamma (PtdInsPKI gamma-90) binds, by means of a short carboxy-terminal peptide, to the FERM domain of talin, and is strongly activated by this interaction (PMID:12422219)
• we show that the type I phosphatidylinositol phosphate kinase isoform-gamma 661 (PIPKI gamma 661), an enzyme that makes PtdIns(4,5)P(2), is targeted to focal adhesions by an association with talin (PMID:12422220)
• The short splice variant of type I phosphatidylinositol 4-phosphate 5-kinase gamma (PIP5KIgamma87) as the major contributor of the PIP(2) pool that supports G protein-coupled receptor (GPCR)-mediated IP(3) generation. (PMID:15611330)
• PIPKIgamma661 enzyme is involved in the AP2-mediated endocytosis of transferrin. (PMID:16707488)
• a positive feedback loop consisting of endocytic cargo proteins, AP-2mu, and PIPK type I which may provide a specific pool of PI(4,5)P(2) dedicated to clathrin/AP-2-dependent receptor internalization (PMID:16880396)
• Localization of ezrin in adherens junctions is regulated by Rac in a manner involving PIPK. (PMID:17229424)
• results reveal a novel mechanism where PIPKIgamma serves as a scaffold, linking E-cadherin to adaptor complexes and the trafficking machinery, and a regulator of trafficking events via the spatial generation of phosphatidylinositol-4,5-bisphosphate (PMID:17261850)
• PIP5K1C is required for EGF-stimulated diectional cell migration. (PMID:17635937)
• A single homozygous substitution of aspartic acid with asparagine at amino acid 253 in PIP5K1C causes lethal contractural syndrome type 3> (PMID:17701898)
• identify a previously unknown function for PIPKIgamma661 as a novel component of the backness signal that regulates rear retraction during chemotaxis (PMID:17928408)
• 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)
• Data have identified two novel C-terminal splice variants of PIPKIgamma that are expressed in multiple tissue types, display PIPK activity in vitro abd have distinct subcellular targeting. (PMID:19548880)
• multiple interactions between PIPKI gamma-p90 and AP-2 lead to spatiotemporally controlled PI(4,5)P(2) synthesis during clathrin-mediated synaptic vesicle endocytosis (PMID:19903820)
• Type I gamma phosphatidylinositol phosphate kinase modulates invasion and proliferation and its expression correlates with poor prognosis in breast cancer. (PMID:20074374)
• Data show that glycation end products (AGE) increase PIP2 production, arachidonic acid release and reactive oxygen species via cytosolic phospholipase A2 activation, and inhibit Na+ K+ ATPase surface expression via PIP5Kgamma. (PMID:20435073)
• SIRT1 deacetylated two specific lysine residues (K265/K268) in PIP5Kgamma and enhanced PIP5Kgamma enzyme activity. (PMID:20668706)
• EZH2 regulates neuronal differentiation of mesenchymal stem cells through PIP5K1C-dependent calcium signaling. (PMID:21216957)
• A novel mechanism in which PIPKIgamma expression and catalytic activity enhance beta-catenin nuclear translocation and expression of its target genes to promote tumorigenic phenotypes. (PMID:21303971)
• PIPKIgamma positively regulates focal adhesion dynamics and cancer invasion, most probably through PIP-mediated vinculin activation. (PMID:21931851)
• PIPKIgamma and phosphatidyl inositol phosphate pools at nascent E-cadherin contacts cue Exo70 targeting and orient the tethering of exocyst-associated E-cadherin (PMID:22049025)
• This study uncovers a novel mechanism where a phosphoinositide-synthesizing enzyme, PIPKIgammai2, functions with the proto-oncogene Src, to regulate oncogenic signaling (PMID:24151076)
• PIPKIgamma binds to the cryptic polo-box domain of PLK4 and reduces the kinase activity of PLK4. (PMID:24434581)
• Loss of PIPKIgamma or its focal adhesion-targeting variant, PIPKIgammai2, impaired PI3K/Akt activation upon stimulation with growth factors or extracellular matrix proteins in different tumor cells. (PMID:26070568)
• results suggested that Akt-mediated PIP5Kgamma90 S555 phosphorylation is a novel regulatory point for talin binding to control PIP2 level at the FAs, thereby modulating FA dynamics and cell motility. (PMID:26149501)
• PIPKIgamma and INPP5E localize to the centrosome and coordinate the initiation of ciliogenesis. (PMID:26916822)
• FAK sustained the active integrin conformation by maintaining talin association with Rab11 endosomes in a type I phosphatidylinositol phosphate kinase (PIPKIgamma)-dependent manner. (PMID:27043085)
• PIPKIgammai5, NEDD4-1, and Mig6 form a novel molecular nexus that controls EGFR activation and downstream signaling. (PMID:27557663)
• These data reveal a novel function for PKD1 as a regulator of focal adhesion dynamics and by identifying PIP5Klgamma as a novel PKD1 substrate provide mechanistic insight into this process. (PMID:27775029)
• These data suggest that S6K1-mediated PIPKIgamma90 phosphorylation regulates cell migration and invasion by controlling PIPKIgamma90 degradation. (PMID:27780861)
• PIPKIgamma promotes the transcription of the PD-L1 gene by activating the NF-kappaB pathway in these cells. These results demonstrate that PIPKIgamma-dependent expression of PD-L1 is likely important for the progression of triple negative breast cancer. (PMID:28465490)
• High expression of PIP5K1-gamma is associated with colorectal cancer. (PMID:28560454)
• The Btk-dependent PIP5K1gamma lipid kinase activation by Fas counteracts FasL-induced cell death. (PMID:28879546)
• PIP5K1C was significantly associated with Alcohol Use Disorder in the African ancestry group. However, a replication analysis using an independent sample (N = 3,801) found no significant associations after correction for multiple testing. (PMID:29667742)
• Cdk5-mediated PIPKIgamma90 phosphorylation is essential for cell invasion leading to breast cancer. (PMID:30040488)
• Our findings reveal a new regulatory role of PIPKIgamma in Warburg effect and provide a key contributor in colorectal cancer metabolism with potential therapeutic potentials. (PMID:31105034)
• our observations revealed that high PIPKIgamma expression in tumor cells could induce AKT-mTOR signaling activation. Increased activation of AKT-mTOR increases the phosphorylation levels of STAT3, leading to CCL2 expression and suppressing cancer immune reaction activation. (PMID:31781676)
• 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)
• CLIC1 recruits PIP5K1A/C to induce cell-matrix adhesions for tumor metastasis. (PMID:33079727)
• Temporal involvement of phosphatidylinositol 4-phosphate 5-kinase gamma in differentiation of Z-bands and myofilament bundles as well as intercalated discs in mouse heart at mid-gestation. (PMID:38275211)
• Type I gamma phosphatidylinositol phosphate 5-kinase i5 controls cell sensitivity to interferon. (PMID:38452758)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pip5k1ca	ENSDARG00000076001
danio_rerio	pip5k1cb	ENSDARG00000100313
mus_musculus	Pip5k1c	ENSMUSG00000034902
rattus_norvegicus	Pip5k1c	ENSRNOG00000020577

Paralogs (6): PIP5K1B (ENSG00000107242), PIP5K1A (ENSG00000143398), PIP4K2A (ENSG00000150867), PIP4K2C (ENSG00000166908), PIP5KL1 (ENSG00000167103), PIP4K2B (ENSG00000276293)

Protein

Protein identifiers

Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma — O60331 (reviewed: O60331)

Alternative names: Type I phosphatidylinositol 4-phosphate 5-kinase gamma

All UniProt accessions (3): O60331, A0A7P0T808, A0A7P0TAE7

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. Together with PIP5K1A, is required for phagocytosis, both enzymes regulating different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1/cadherin trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor-stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A has a role during embryogenesis and together with PIP5K1B may have a role immediately after birth.

Subunit / interactions. Interacts with TLN1. Interacts with TLN2; interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity. May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6; interaction stimulates 1-phosphatidylinositol-4-phosphate 5-kinase activity. Interacts with AP2B1. Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C. Interacts with CDH1. Interacts with CSK. Interacts with PLCG1; interaction is abolished upon EGF stimulation. Interacts with LAPTM4B; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C.

Subcellular location. Cell membrane. Endomembrane system. Cytoplasm. Cell junction. Focal adhesion. Adherens junction. Cell projection. Ruffle membrane. Phagocytic cup. Uropodium Cytoplasm. Nucleus.

Tissue specificity. Isoform 1 is strongly expressed in brain and also detected in heart and lung. Isoform 2 is strongly expressed in pancreas and liver and in lesser quantities in brain, heart, lung and kidney. Isoform 3 is detected in large amounts in heart and large intestine, is also present in lung, pancreas and thyroid, and to a lesser extent in brain, stomach and kidney.

Post-translational modifications. Phosphorylation on Ser-650 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-649 is necessary for targeting to focal adhesions. Phosphorylation on Ser-650 and Tyr-649 are mutually exclusive. Phosphorylated by SYK and CSK. Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-639 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-649 enhances binding to tailins (TLN1 and TLN2). According to PubMed:15738269 phosphorylation at Tyr-649 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-650. Acetylation at Lys-265 and Lys-268 seems to decrease lipid 1-phosphatidylinositol-4-phosphate 5-kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells.

Disease relevance. Lethal congenital contracture syndrome 3 (LCCS3) [MIM:611369] A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS3 patients present at birth with severe multiple joint contractures and severe muscle wasting and atrophy, mainly in the legs. Death occurs minutes to hours after birth due to respiratory insufficiency. The phenotype can be distinguished from that of LCCS1 by the absence of hydrops, fractures and multiple pterygia, and from LCCS2 by the absence of neurogenic bladder defect. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (4)

UniProt ID	Names	Canonical?
O60331-1	1, PIPKIgamma-90, PIPKIgamma-668, PIPkinIgamma-a, PIPKIgamma_i2	yes
O60331-2	2, variant 700, PIPKIgamma-700, PIPKIgamma_i4
O60331-3	3, variant 707, PIPKIgamma-707, PIPKIgamma_i5
O60331-4	4, PIPKIgamma-87, PIPKIgamma-640, PIPkinIgamma-b, PIPKIgamma_i1

RefSeq proteins (3): NP_001182662, NP_001287778, NP_036530* (*=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), 7 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)

UniProt features (26 total): modified residue 11, region of interest 4, splice variant 3, mutagenesis site 2, chain 1, domain 1, sequence variant 1, sequence conflict 1, helix 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3H1Z	X-RAY DIFFRACTION	1.83
3H85	X-RAY DIFFRACTION	2.6
2G35	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60331-F1	65.33	0.42

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 (11): 459, 555, 639, 649, 650, 662, 666, 668, 265, 268, 459

Mutagenesis-validated functional residues (2):

Position	Phenotype
650	abolishes binding to tln2. affects localization to focal adhesions.
650	does not affect binding to tln2 and localization to focal adhesions.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-399955	SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling
R-HSA-8856828	Clathrin-mediated endocytosis
R-HSA-9768727	Regulation of CDH1 posttranslational processing and trafficking to plasma membrane

MSigDB gene sets: 251 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_NEUROTRANSMITTER_TRANSPORT, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOCC_RUFFLE, REACTOME_MEMBRANE_TRAFFICKING, CTATGCA_MIR153, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_SYNAPTIC_VESICLE_RECYCLING, GOBP_CELL_CELL_SIGNALING, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (18): phosphatidylinositol biosynthetic process (GO:0006661), phagocytosis (GO:0006909), synaptic vesicle exocytosis (GO:0016079), actin cytoskeleton organization (GO:0030036), neutrophil chemotaxis (GO:0030593), adherens junction assembly (GO:0034333), phosphatidylinositol phosphate biosynthetic process (GO:0046854), synaptic vesicle endocytosis (GO:0048488), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), membrane organization (GO:0061024), clathrin-dependent endocytosis (GO:0072583), cell-cell adhesion (GO:0098609), lipid metabolic process (GO:0006629), exocytosis (GO:0006887), endocytosis (GO:0006897), chemotaxis (GO:0006935), cell adhesion (GO:0007155), phosphatidylinositol metabolic process (GO:0046488)

GO Molecular Function (7): ATP binding (GO:0005524), 1-phosphatidylinositol-4-phosphate 5-kinase activity (GO:0016308), phosphatidylinositol kinase activity (GO:0052742), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (16): phagocytic cup (GO:0001891), uropod (GO:0001931), nucleoplasm (GO:0005654), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), focal adhesion (GO:0005925), endosome membrane (GO:0010008), ruffle membrane (GO:0032587), presynapse (GO:0098793), nucleus (GO:0005634), cytoplasm (GO:0005737), endomembrane system (GO:0012505), membrane (GO:0016020), cell projection (GO:0042995), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
PI Metabolism	1
Semaphorin interactions	1
Negative regulation of the PI3K/AKT network	1
Membrane Trafficking	1
Regulation of CDH1 Expression and Function	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
vesicle-mediated transport	2
plasma membrane	2
biosynthetic process	1
phosphatidylinositol metabolic process	1
endocytosis	1
neurotransmitter secretion	1
regulated exocytosis	1
establishment of localization in cell	1
presynapse	1
vesicle-mediated transport in synapse	1
synaptic vesicle cycle	1
signal release from synapse	1
cytoskeleton organization	1
actin filament-based process	1
granulocyte chemotaxis	1
neutrophil migration	1
cell-cell junction assembly	1
adherens junction organization	1
glycerophospholipid biosynthetic process	1
synaptic vesicle recycling	1
presynaptic endocytosis	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	1
cellular component organization	1
receptor-mediated endocytosis	1
cell adhesion	1
primary metabolic process	1
secretion by cell	1
vesicle fusion to plasma membrane	1
vesicle budding from membrane	1
membrane invagination	1
import into cell	1
response to chemical	1
taxis	1
cellular process	1
phosphorus metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
phosphatidylinositol kinase activity	1

Protein interactions and networks

STRING

1748 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIP5K1C	TLN1	Q9Y490	949
PIP5K1C	TLN2	Q9Y4G6	940
PIP5K1C	GLE1	Q53GS7	835
PIP5K1C	CHST15	Q7LFX5	830
PIP5K1C	AP2M1	P20172	780
PIP5K1C	SON	P18583	706
PIP5K1C	ERBB3	P21860	594
PIP5K1C	VCL	P18206	556
PIP5K1C	PI4K2A	Q9BTU6	551
PIP5K1C	PI4KB	P78405	541
PIP5K1C	PLD2	O14939	536
PIP5K1C	EXOC7	Q9UPT5	532
PIP5K1C	ZYX	Q15942	523
PIP5K1C	VASP	P50552	519
PIP5K1C	ARF6	P26438	507

IntAct

33 interactions, top by confidence:

A	B	Type	Score
PIK3CA	PIK3R2	psi-mi:“MI:0914”(association)	0.900
TLN1	PIP5K1C	psi-mi:“MI:0407”(direct interaction)	0.610
PIP5K1C	TLN1	psi-mi:“MI:0407”(direct interaction)	0.610
RABGGTB	PIPSL	psi-mi:“MI:0914”(association)	0.530
Tln1	PIP5K1C	psi-mi:“MI:0407”(direct interaction)	0.440
PIP5K1C	PIP5K1C	psi-mi:“MI:0915”(physical association)	0.400
PIP5K1C	TPTE	psi-mi:“MI:0915”(physical association)	0.400
NYAP1	PIP5K1C	psi-mi:“MI:0915”(physical association)	0.400
ITGB3	PIP5K1C	psi-mi:“MI:0915”(physical association)	0.400
COQ2	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
SOAT1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
VDAC1	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
PIP5K1A	NRP1	psi-mi:“MI:0914”(association)	0.350
VAV1	DDX39A	psi-mi:“MI:0914”(association)	0.350
ARHGEF1	PIP5K1C	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
PIP5K1C	SNX4	psi-mi:“MI:0914”(association)	0.350
EAF1	C1orf226	psi-mi:“MI:0914”(association)	0.350
FBXO3	PIP5K1C	psi-mi:“MI:0914”(association)	0.350
INO80E	CHD1	psi-mi:“MI:0914”(association)	0.350
PIP4K2A	SAP18	psi-mi:“MI:0914”(association)	0.350
PIP5K1A	RRP8	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): PIP5K1C (Affinity Capture-Western), PIP5K1C (Affinity Capture-Western), PIP5K1C (Affinity Capture-RNA), PIP5K1C (Affinity Capture-Western), LAPTM4B (Affinity Capture-Western), PIP5K1C (Affinity Capture-Western), PIP5K1C (Reconstituted Complex), SNX5 (Affinity Capture-Western), PIP5K1C (Affinity Capture-Western), PIP5K1C (Affinity Capture-MS), PIP5K1C (Affinity Capture-MS), PIP5K1C (Affinity Capture-MS), PIP5K1C (Affinity Capture-MS), PIP5K1C (Affinity Capture-Western), PIP5K1C (Co-crystal Structure)

ESM2 similar proteins: A2A3N6, A8WRV1, B2RRD7, B9EHT4, D3ZSI8, G5EFI8, O14986, O42626, O48709, O60331, O70161, O94823, P0C5E7, P34442, P55201, P70181, P70182, P90895, Q05999, Q21017, Q22712, Q3V0G7, Q4P3S3, Q56YP2, Q5CZZ9, Q5I6B8, Q5R686, Q5SVQ0, Q5U243, Q5ZJ58, Q6P158, Q6P5D3, Q810T5, Q8CFI0, Q8L796, Q8L850, Q8RY89, Q95Q62, Q95QC4, Q96DZ5

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

8 interactions.

A	Effect	B	Mechanism
CDK5	down-regulates	PIP5K1C	phosphorylation
SRC	up-regulates	PIP5K1C	phosphorylation
PIP5K1C	“down-regulates activity”	“1-phosphatidyl-1D-myo-inositol 4-phosphate(3-)”	“chemical modification”
PIP5K1C	“down-regulates activity”	ATP(4-)	“chemical modification”
PIP5K1C	“up-regulates quantity”	“1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate(5-)”	“chemical modification”
PIP5K1C	“up-regulates quantity”	ADP(3-)	“chemical modification”
RPS6KB1	“down-regulates quantity by destabilization”	PIP5K1C	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	19.4×	6e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	6
Likely pathogenic	1
Uncertain significance	125
Likely benign	60
Benign	61

Top pathogenic / likely-pathogenic (7)

Variant ID	HGVS	Classification
1172538	NM_012398.3(PIP5K1C):c.662A>G (p.Tyr221Cys)	Pathogenic
3340944	NM_012398.3(PIP5K1C):c.625C>T (p.Leu209Phe)	Pathogenic
3780979	NM_012398.3(PIP5K1C):c.700C>T (p.Arg234Cys)	Pathogenic
4615	NM_012398.3(PIP5K1C):c.757G>A (p.Asp253Asn)	Pathogenic
871901	NM_012398.3(PIP5K1C):c.1127+1G>A	Pathogenic
871902	NM_012398.3(PIP5K1C):c.688_689del (p.Gly230fs)	Pathogenic
3377275	NM_012398.3(PIP5K1C):c.777_778dup (p.Lys260fs)	Likely pathogenic

SpliceAI

4530 predictions. Top by Δscore:

Variant	Effect	Δscore
19:3633167:TTA:T	acceptor_gain	1.0000
19:3633170:C:CC	acceptor_gain	1.0000
19:3638882:A:AC	donor_gain	1.0000
19:3638883:C:CC	donor_gain	1.0000
19:3639012:CCACC:C	acceptor_gain	1.0000
19:3639013:CACC:C	acceptor_gain	1.0000
19:3639013:CACCC:C	acceptor_gain	1.0000
19:3639014:ACC:A	acceptor_gain	1.0000
19:3639015:CC:C	acceptor_gain	1.0000
19:3639015:CCC:C	acceptor_gain	1.0000
19:3639016:CC:C	acceptor_gain	1.0000
19:3639017:C:CC	acceptor_gain	1.0000
19:3641703:AC:A	donor_gain	1.0000
19:3641704:CC:C	donor_gain	1.0000
19:3641711:T:TA	donor_gain	1.0000
19:3641714:T:TA	donor_gain	1.0000
19:3641805:GCGGC:G	acceptor_gain	1.0000
19:3641806:CGGC:C	acceptor_gain	1.0000
19:3641806:CGGCC:C	acceptor_gain	1.0000
19:3641810:C:CC	acceptor_gain	1.0000
19:3641810:C:CG	acceptor_loss	1.0000
19:3641811:T:G	acceptor_loss	1.0000
19:3642939:CCTGC:C	acceptor_loss	1.0000
19:3644084:CACCT:C	donor_loss	1.0000
19:3644086:C:CG	donor_loss	1.0000
19:3644247:CAGGG:C	acceptor_gain	1.0000
19:3644248:AGGG:A	acceptor_gain	1.0000
19:3644249:GGG:G	acceptor_gain	1.0000
19:3644249:GGGC:G	acceptor_loss	1.0000
19:3644250:GG:G	acceptor_gain	1.0000

AlphaMissense

4360 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:3645988:A:G	F444S	1.000
19:3645991:A:T	V443D	1.000
19:3646005:G:C	F438L	1.000
19:3646005:G:T	F438L	1.000
19:3646007:A:G	F438L	1.000
19:3646015:A:G	F435S	1.000
19:3646018:C:A	R434L	1.000
19:3646018:C:G	R434P	1.000
19:3646019:G:C	R434G	1.000
19:3646019:G:T	R434S	1.000
19:3646024:G:T	A432D	1.000
19:3646025:C:G	A432P	1.000
19:3646028:A:C	Y431D	1.000
19:3646028:A:G	Y431H	1.000
19:3646029:G:C	F430L	1.000
19:3646029:G:T	F430L	1.000
19:3646031:A:G	F430L	1.000
19:3646036:G:A	P428L	1.000
19:3646036:G:T	P428H	1.000
19:3646037:G:A	P428S	1.000
19:3646037:G:T	P428T	1.000
19:3646043:G:C	H426D	1.000
19:3646045:A:T	V425D	1.000
19:3646048:G:A	S424F	1.000
19:3646048:G:T	S424Y	1.000
19:3646051:A:T	V423E	1.000
19:3647339:C:T	G420E	1.000
19:3647348:A:T	V417D	1.000
19:3647351:A:G	L416P	1.000
19:3647355:C:G	A415P	1.000

dbSNP variants (sampled 300 via entrez): RS1000007821 (19:3702188 A>G), RS1000047559 (19:3677634 T>C), RS1000138733 (19:3679554 C>T), RS1000158283 (19:3679081 A>G), RS1000181473 (19:3693575 A>G), RS1000194242 (19:3638534 C>A), RS1000221521 (19:3690705 C>T), RS1000229481 (19:3671963 C>A,T), RS1000249885 (19:3655285 G>C), RS1000296192 (19:3635430 T>C), RS1000316527 (19:3700125 G>A), RS1000420041 (19:3678408 G>A,T), RS1000431643 (19:3685646 C>A,T), RS1000470288 (19:3676225 C>T), RS1000550499 (19:3643556 G>GT)

Disease associations

OMIM: gene MIM:606102 | disease phenotypes: MIM:611369, MIM:254130

GenCC curated gene-disease

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Strong	Autosomal dominant
lethal congenital contracture syndrome 3	Strong	Autosomal recessive
neurodevelopmental disorder	Moderate	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
PIP5K1C-related neurodevelopmental disorder	Strong	AD

Mondo (5): PIP5K1C-related neurodevelopmental disorder (MONDO:1010145), lethal congenital contracture syndrome 3 (MONDO:0012656), Miyoshi muscular dystrophy 1 (MONDO:0024545), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (2): Lethal congenital contracture syndrome type 3 (Orphanet:137783), Miyoshi myopathy (Orphanet:45448)

HPO phenotypes

6 total (6 of 6 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002093	Respiratory insufficiency
HP:0002804	Arthrogryposis multiplex congenita
HP:0002828	Multiple joint contractures
HP:0003202	Skeletal muscle atrophy
HP:0003811	Neonatal death

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625
C566961	Lethal Congenital Contractural Syndrome 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1908383 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 57,057 (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
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL230011	TG100-115	2	1,504
CHEMBL475251	R-406	2	762
CHEMBL5083772	BIIB-091	2	86
CHEMBL1908394	GSK-461364	1	1,093
CHEMBL494089	GSK-690693	1	2,061

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

PharmGKB clinical annotations

8 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs10405681	Toxicity	3	ethanol	Alcohol abuse
rs10419980	Toxicity	3	ethanol	Alcohol abuse
rs10432303	Toxicity	3	ethanol	Alcohol abuse
rs1476592	Toxicity	3	ethanol	Alcohol abuse
rs2074957	Toxicity	3	ethanol	Alcohol abuse
rs4432372	Toxicity	3	ethanol	Alcohol abuse
rs4807493	Toxicity	3	ethanol	Alcohol abuse
rs8109485	Toxicity	3	ethanol	Alcohol abuse

PharmGKB variants

16 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4807493	PIP5K1C	3	0.00	1	ethanol
rs3746124	PIP5K1C		0.00	0
rs10405681	PIP5K1C	3	0.00	1	ethanol
rs1004323	PIP5K1C		0.00	0
rs12460780	PIP5K1C		0.00	0
rs2270083	PIP5K1C		0.00	0
rs12984273	PIP5K1C		0.00	0
rs2074957	PIP5K1C	3	0.00	1	ethanol
rs10432303	PIP5K1C	3	0.00	1	ethanol
rs757454	PIP5K1C		0.00	0
rs8109485	PIP5K1C	3	0.00	1	ethanol
rs11672559	PIP5K1C		0.00	0
rs1476592	PIP5K1C	3	0.00	1	ethanol
rs10419980	PIP5K1C	3	0.00	1	ethanol
rs740873	PIP5K1C		0.00	0
rs4432372	PIP5K1C	3	0.00	1	ethanol

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol phosphate kinases

ChEMBL bioactivities

88 potent at pChembl≥5 of 105 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	CHEMBL5646720
9.10	IC50	0.8	nM	CHEMBL5639468
9.08	IC50	0.83	nM	CHEMBL5646581
8.89	IC50	1.3	nM	CHEMBL5191668
8.85	IC50	1.4	nM	CHEMBL5647421
8.82	IC50	1.5	nM	CHEMBL5182242
8.68	IC50	2.1	nM	CHEMBL5646709
8.62	IC50	2.4	nM	CHEMBL5647624
8.57	IC50	2.7	nM	CHEMBL5639405
8.54	IC50	2.9	nM	CHEMBL5647063
8.52	IC50	3	nM	CHEMBL5646941
8.44	IC50	3.6	nM	CHEMBL5194835
8.42	IC50	3.8	nM	CHEMBL5195505
8.42	IC50	3.8	nM	CHEMBL5646459
8.41	IC50	3.9	nM	CHEMBL5173406
8.23	IC50	5.9	nM	CHEMBL5208791
8.23	IC50	5.9	nM	CHEMBL5639609
8.19	IC50	6.5	nM	CHEMBL5641764
8.17	IC50	6.7	nM	CHEMBL5202114
8.02	IC50	9.5	nM	CHEMBL5171272
7.96	IC50	11	nM	CHEMBL5171867
7.94	IC50	11.6	nM	CHEMBL5208569
7.92	IC50	12	nM	CHEMBL5195735
7.85	IC50	14	nM	CHEMBL5646361
7.77	IC50	17	nM	CHEMBL5203228
7.75	Kd	18	nM	CHEMBL1241674
7.70	IC50	20	nM	CHEMBL5208135
7.66	IC50	22	nM	CHEMBL5171431
7.64	IC50	23	nM	CHEMBL5191055
7.60	IC50	25	nM	CHEMBL5639728
7.46	IC50	35	nM	CHEMBL5198244
7.46	IC50	35	nM	CHEMBL5641817
7.41	IC50	39	nM	CHEMBL5206569
7.39	IC50	41	nM	CHEMBL4303547
7.39	IC50	41	nM	CHEMBL5203889
7.32	IC50	48	nM	CHEMBL5186780
7.21	IC50	61	nM	CHEMBL5639144
7.19	IC50	65	nM	CHEMBL5639396
7.18	IC50	66.6	nM	CHEMBL5200538
7.16	IC50	70	nM	CHEMBL5639780
7.11	Kd	77	nM	CHEMBL4554938
7.06	IC50	88	nM	CHEMBL5641672
7.05	IC50	90	nM	CHEMBL5641566
6.89	Kd	130	nM	R-406
6.85	IC50	140	nM	CHEMBL5639495
6.85	IC50	140	nM	CHEMBL5647360
6.82	IC50	150	nM	CHEMBL5170319
6.82	IC50	150	nM	CHEMBL5646821
6.82	IC50	150	nM	CHEMBL5641784
6.80	IC50	160	nM	CHEMBL5201959

PubChem BioAssay actives

83 with measured affinity, of 267 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-cyclopropyl-3-(6-methylsulfonyl-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0002	uM
3-(6-chloro-1H-indol-2-yl)-N-cyclopropylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0008	uM
N-cyclopropyl-3-(7-fluoro-6-methylsulfonyl-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0008	uM
N-[4-(3-acetamido-5-anilinophenyl)-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0013	uM
3-(6-cyano-1H-indol-2-yl)-N-cyclopropylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0014	uM
N-[4-[3-anilino-5-[(2-hydroxyacetyl)amino]phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0015	uM
N-cyclopropyl-3-(6-methyl-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0021	uM
N-cyclopropyl-3-(6-fluoro-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0024	uM
3-(6-chloro-7-fluoro-1H-indol-2-yl)-N-cyclopropylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclopentane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0027	uM
3-(6-chloro-7-fluoro-1H-indol-2-yl)-N-cyclopropylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,3’-oxetane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0029	uM
N-cyclopropyl-3-(6-methoxy-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0030	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-methylbenzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0036	uM
N-[4-[3-anilino-5-(methanesulfonamido)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0038	uM
3-(6-chloro-7-fluoro-1H-indol-2-yl)-N-(2-methoxyethyl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0038	uM
N-(2-amino-2-oxoethyl)-3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]benzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0039	uM
N-[4-[3-anilino-5-(methylamino)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0059	uM
3-(6-chloro-7-fluoro-1H-indol-2-yl)-N-cyclopropylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0059	uM
3-(6-chloro-7-fluoro-1H-indol-2-yl)-N-(oxetan-3-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0065	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-(1,3-dioxolan-2-ylmethyl)benzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0067	uM
N-[4-[3-anilino-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0095	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-[2-(dimethylamino)ethyl]benzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0110	uM
3-(2-acetamido-4-pyridinyl)-5-anilino-N-methylbenzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0116	uM
N-[4-[3-(4-fluoroanilino)-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0120	uM
N-cyclopropyl-3-(1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0140	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-[3-(dimethylamino)propyl]benzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0170	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624751: Binding constant for PIP5K1C kinase domain	kd	0.0180	uM
N-[4-[3-anilino-5-[2-(dimethylamino)ethoxy]phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0200	uM
N-[4-[3-anilino-5-[(4-methylpiperazin-1-yl)methyl]phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0220	uM
N-[4-[3-anilino-5-(methylsulfamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0230	uM
N-cyclopropyl-3-(1H-indol-2-yl)-4,4-dimethyl-1,6-dihydropyrrolo[3,4-c]pyrazole-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0250	uM
N-[6-[3-(4-fluoroanilino)-5-(methylcarbamoyl)phenyl]pyrimidin-4-yl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0350	uM
3-(1H-indol-2-yl)-N-propan-2-ylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0350	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-(1,3-dioxolan-2-ylmethyl)-N-methylbenzamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0390	uM
N-[4-[3-anilino-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxolane-3-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0410	uM
2-anilino-5-(cyclohexanecarbonylamino)-1,3-thiazole-4-carboxamide	1888782: Inhibition of N-terminal His6-tagged full length recombinant human PIP5K1gamma by microfluidic mobility shift assay	ic50	0.0410	uM
N-[4-[3-(3-fluoroanilino)-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0480	uM
N-cyclopropyl-3-(1H-indol-2-yl)-4-methyl-4,6-dihydro-1H-pyrrolo[3,4-c]pyrazole-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0610	uM
N-cyclopropyl-3-(7-fluoro-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0650	uM
N-[4-[3-[acetyl(methyl)amino]-5-anilinophenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.0666	uM
N-cyclopropyl-3-(5-fluoro-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0700	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	2189155: Binding affinity to PIP5K1C (unknown origin) assessed as dissociation constant	kd	0.0770	uM
N-cyclopropyl-3-(1H-indol-2-yl)-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazole-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0880	uM
N-(azetidin-3-yl)-3-(6-chloro-7-fluoro-1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.0900	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	624751: Binding constant for PIP5K1C kinase domain	kd	0.1300	uM
N-cyclopropyl-3-(1H-indol-2-yl)-1,4,6,7-tetrahydropyrazolo[4,3-c]pyridine-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.1400	uM
3-(1H-benzimidazol-2-yl)-N-cyclopropylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.1400	uM
N-[4-[3-(2-fluoroanilino)-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.1500	uM
3-(1H-indol-2-yl)-N-phenylspiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-carboxamide	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.1500	uM
cyclopropyl-[3-(1H-indol-2-yl)spiro[1,6-dihydropyrrolo[3,4-c]pyrazole-4,1’-cyclobutane]-5-yl]methanone	2144402: Inhibition of N-terminal 6His-tagged full-length recombinant human PIP5K1C expressed in baculovirus infected Sf21 cells using PI4P/PS as substrate incubated for 60 mins in presence of ATP by ADP-Glo assay	ic50	0.1500	uM
N-[5-chloro-4-[3-(4-fluoroanilino)-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888785: Inhibition of PIP5Kgamma (unknown origin)	ic50	0.1600	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cisplatin	decreases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	increases methylation, affects cotreatment	1
dicrotophos	increases expression	1
chloroacetaldehyde	affects expression	1
bisphenol A	affects cotreatment, increases methylation	1
titanium dioxide	decreases methylation	1
trichostatin A	affects expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
beta-methylcholine	affects expression	1
clothianidin	decreases expression	1
abrine	decreases expression	1
Temozolomide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation, decreases methylation	1
Leflunomide	decreases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	decreases phosphorylation	1
Cannabinoids	affects methylation, increases abundance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Deoxycholic Acid	decreases response to substance	1
Clodronic Acid	affects expression	1
Oxygen	decreases expression	1
Ozone	affects expression, increases abundance	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Urethane	increases expression	1

ChEMBL screening assays

116 unique, capped per target: 116 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1175217	Binding	Inhibition of PIP5K1C at 10 uM	Broad spectrum alkynyl inhibitors of T315I Bcr-Abl. — Bioorg Med Chem Lett

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_B2AV	Abcam HeLa PIP5K1C KO	Cancer cell line	Female
CVCL_D7XL	Ubigene A-549 PIP5K1C KO	Cancer cell line	Male
CVCL_D8T2	Ubigene HCT 116 PIP5K1C KO	Cancer cell line	Male
CVCL_D9NK	Ubigene HEK293 PIP5K1C KO	Transformed cell line	Female
CVCL_E0KX	Ubigene HeLa PIP5K1C KO	Cancer cell line	Female
CVCL_TD94	HAP1 PIP5K1C (-) 1	Cancer cell line	Male
CVCL_TD95	HAP1 PIP5K1C (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism