PI4KA

Summary

PI4KA (phosphatidylinositol 4-kinase alpha, HGNC:8983) is a protein-coding gene on chromosome 22q11.21, encoding Phosphatidylinositol 4-kinase alpha (P42356). Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate. It is a selective cancer dependency (DepMap: 90.0% of cell lines).

This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms.

Source: NCBI Gene 5297 — RefSeq curated summary.

At a glance

• Gene–disease (curated): polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (Definitive, GenCC)
• GWAS associations: 3
• Clinical variants (ClinVar): 560 total — 22 pathogenic, 26 likely-pathogenic
• Phenotypes (HPO): 140
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• Cancer dependency (DepMap): dependent in 90.0% of screened cell lines
• MANE Select transcript: NM_058004

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8983
Approved symbol	PI4KA
Name	phosphatidylinositol 4-kinase alpha
Location	22q11.21
Locus type	gene with protein product
Status	Approved
Aliases	PI4K-ALPHA, pi4K230
Ensembl gene	ENSG00000241973
Ensembl biotype	protein_coding
OMIM	600286
Entrez	5297

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 18 protein_coding, 13 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000255882, ENST00000399213, ENST00000449120, ENST00000462210, ENST00000466162, ENST00000466394, ENST00000466772, ENST00000475414, ENST00000477245, ENST00000477368, ENST00000482030, ENST00000484220, ENST00000485123, ENST00000485950, ENST00000485963, ENST00000489966, ENST00000492581, ENST00000494113, ENST00000880811, ENST00000880812, ENST00000880813, ENST00000939409, ENST00000939410, ENST00000939411, ENST00000939412, ENST00000939413, ENST00000939414, ENST00000939415, ENST00000939416, ENST00000957001, ENST00000957002, ENST00000957003, ENST00000957004

RefSeq mRNA: 3 — MANE Select: NM_058004 NM_001362862, NM_001362863, NM_058004

CCDS: CCDS33603

Canonical transcript exons

ENST00000255882 — 55 exons

Exon	Start	End
ENSE00001620613	20744628	20744720
ENSE00001634710	20747583	20747702
ENSE00001636327	20751674	20751755
ENSE00001644702	20752903	20753027
ENSE00001654715	20753110	20753180
ENSE00001661705	20734395	20734553
ENSE00001710190	20798584	20798687
ENSE00001786226	20742608	20742764
ENSE00001792161	20796146	20796314
ENSE00001839790	20707691	20708098
ENSE00003463977	20709908	20709997
ENSE00003466849	20765585	20765693
ENSE00003467040	20710699	20710858
ENSE00003471014	20729313	20729506
ENSE00003472717	20733736	20733843
ENSE00003474180	20819641	20819900
ENSE00003474947	20765100	20765236
ENSE00003483612	20711341	20711461
ENSE00003484938	20727230	20727397
ENSE00003488341	20727774	20727864
ENSE00003502775	20726488	20726541
ENSE00003509500	20712693	20712797
ENSE00003515404	20804300	20804400
ENSE00003520208	20709296	20709379
ENSE00003523646	20714628	20714700
ENSE00003534742	20810967	20811032
ENSE00003535601	20804974	20805165
ENSE00003547793	20807362	20807458
ENSE00003549460	20813358	20813506
ENSE00003550076	20732971	20733098
ENSE00003551725	20729632	20729711
ENSE00003560817	20712486	20712611
ENSE00003562568	20718693	20718822
ENSE00003564578	20751293	20751376
ENSE00003564903	20799093	20799276
ENSE00003567417	20799671	20799766
ENSE00003568190	20717708	20717778
ENSE00003568806	20742228	20742355
ENSE00003575792	20820539	20820611
ENSE00003579791	20721298	20721418
ENSE00003583961	20838615	20838731
ENSE00003589088	20761304	20761386
ENSE00003595697	20793193	20793243
ENSE00003599476	20714458	20714528
ENSE00003601267	20834562	20834655
ENSE00003604406	20713281	20713390
ENSE00003604552	20801973	20802105
ENSE00003606103	20824326	20824414
ENSE00003612620	20803191	20803320
ENSE00003641217	20749905	20749994
ENSE00003649653	20858570	20858811
ENSE00003666817	20818483	20818549
ENSE00003678829	20734043	20734194
ENSE00003684445	20764817	20764950
ENSE00003684671	20729892	20730011

Expression profiles

Bgee: expression breadth ubiquitous, 143 present calls, max score 99.02.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 28.0934 / max 458.6684, expressed in 1817 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193212	26.7836	1817
193213	0.7847	361
193211	0.1924	71
193214	0.1823	73
193207	0.1438	49
193215	0.0066	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
superior frontal gyrus	UBERON:0002661	99.02	gold quality
right frontal lobe	UBERON:0002810	98.79	gold quality
Brodmann (1909) area 9	UBERON:0013540	98.40	gold quality
frontal cortex	UBERON:0001870	98.39	gold quality
frontal lobe	UBERON:0016525	98.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.31	gold quality
primary visual cortex	UBERON:0002436	98.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	98.18	gold quality
cerebellum	UBERON:0002037	98.06	gold quality
cerebellar cortex	UBERON:0002129	98.05	gold quality
cerebellar hemisphere	UBERON:0002245	98.05	gold quality
prefrontal cortex	UBERON:0000451	98.03	gold quality
anterior cingulate cortex	UBERON:0009835	97.84	gold quality
cerebral cortex	UBERON:0000956	97.83	gold quality
brain	UBERON:0000955	97.14	gold quality
nucleus accumbens	UBERON:0001882	97.02	gold quality
pituitary gland	UBERON:0000007	96.94	gold quality
putamen	UBERON:0001874	96.51	gold quality
caudate nucleus	UBERON:0001873	96.49	gold quality
adenohypophysis	UBERON:0002196	96.46	gold quality
cortical plate	UBERON:0005343	96.18	gold quality
Ammon’s horn	UBERON:0001954	96.08	gold quality
temporal lobe	UBERON:0001871	95.74	gold quality
amygdala	UBERON:0001876	95.68	gold quality
hypothalamus	UBERON:0001898	95.62	gold quality
granulocyte	CL:0000094	95.45	gold quality
body of uterus	UBERON:0009853	95.40	gold quality
sural nerve	UBERON:0015488	95.34	gold quality
right testis	UBERON:0004534	95.33	gold quality
left testis	UBERON:0004533	95.24	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.17
E-CURD-112	yes	7.38
E-MTAB-9543	yes	6.78
E-ENAD-20	no	1247.15

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting PI4KA, 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-4789-5P	99.98	70.76	2721
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-219A-5P	99.91	73.36	735
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-4648	99.91	67.00	710
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-4782-3P	99.88	73.31	735
HSA-MIR-6766-3P	99.88	73.38	732
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-1825	99.72	68.11	1089
HSA-MIR-6516-3P	99.65	68.57	1238
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-199A-5P	99.51	69.71	1107
HSA-MIR-199B-5P	99.51	69.74	1098
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-6839-3P	99.39	68.86	1301
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-324-3P	99.26	66.31	1034
HSA-MIR-4763-3P	99.10	67.83	2649
HSA-MIR-1914-5P	97.83	66.21	807
HSA-MIR-1226-5P	96.50	65.28	643

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 90.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• parallel activation by extracellular calcium-sensing receptor (PMID:11907035)
• PI4KIIIbeta (PIK4CB) and PI4KIIalpha (PIK4CA) localize to discrete subcompartments of the Golgi complex in Madin-Darby canine kidney (MDCK) cells. (PMID:15634669)
• nuclear phosphatidylinositol 4-phosphate, and consequently, synthesis of polyphosphoinositides are required for a correct nuclear function (PMID:16606619)
• These experiments suggest the participation of PI4K230 in a DNase and RNase sensitive complex with a unique localization and function in the nucleolus. (PMID:17131383)
• PI4KIIalpha or PI4KIIbeta knockdown, but not type III PI4Kbeta knockdown, inhibits Listeria internalization. (PMID:17555516)
• The PIK4CA gene is located in the chromosome 22q11 deletion syndrome region, which is of particular interest because it has been implicated in schizophrenia. (PMID:17893707)
• These results indicate that a small fraction of the cellular PI4K activity is sufficient to maintain plasma membrane phosphoinositide pools. (PMID:18077555)
• The present study suggests that the PIK4CA gene does not play a significant role in the vulnerability to METH use disorder in the Japanese population. (PMID:18521859)
• The putative bipartite nuclear localization signal(NLS) itself is a nucleolar targeting signal, and for nuclear import PI4K230 requires a larger sequence around it or, alternatively, the monopartite NLS. (PMID:18585705)
• Failure to confirm the association between the PIK4CA gene and schizophrenia in a Japanese population is reported. (PMID:18615484)
• Association of the PIK4CA schizophrenia-susceptibility gene in adults with the 22q11.2 deletion syndrome is reported. (PMID:18646052)
• the PI4KA gene was shown to be essential for the replication of all HCV genotypes tested (PMID:19304308)
• genetic or pharmacological modulation of PI4KA and PI4KB inhibits multiple genotypes of HCV (PMID:19605471)
• our library screening completed data on the clathrin-mediated endocytosis-dependant entry route of HCV and identified 2 kinases, PI4KIIIalpha and beta, as relevant potential therapeutic targets. (PMID:19608626)
• No strong association between PIK4CA and psychosis in people with 22q11.2 deletion syndrome (PMID:20052689)
• Data suggest that Rab1 contributes to the specificity and timing of GBF1 recruitment by activating PI4KIIIalpha, and that the PtdIns(4)P produced then allows GBF1 to bind to Golgi membranes and activate Arf1. (PMID:20530568)
• This analysis suggests that the direct activation of a lipid kinase PI4KA by hepatitis C virus NS5A contributes critically to the integrity of the membranous viral replication complex. (PMID:21238945)
• PI4KIIIalpha is an essential host factor that supports HCV proliferation and therefore PI4KIIIalpha may be a legitimate target for anti-HCV therapy. (PMID:21297162)
• Study identify the molecular chaperone Hsp90 as a binding partner of PI4KIIbeta, but not of PI4KIIalpha. (PMID:21330372)
• confirmed the high copy number of PI4KIIIalpha transcript in K562 cells along with several genes located in the same region in Chr22, including two pseudogenes that cover most exons coding for isoform 1, consistent with chromosome amplification (PMID:21601653)
• These results suggest that hepatitis C virus NS5A modulation of PI4KA-dependent phosphatidylinositol 4-phosphate production influences replication complex formation. (PMID:21697487)
• PI4KA is necessary for the local enrichment of PI 4-phosphate at the hepatitis c virus membranous web. (PMID:22022594)
• Phosphatidylinositol 4-kinase IIalpha is palmitoylated by Golgi-localized palmitoyltransferases in cholesterol-dependent manner (PMID:22535966)
• Cell culture studies with Phosphatidylinositol-4-kinase IIIalpha inhibitors demonstrated that the kinase activity was essential for hepatitis C virus RNA replication. (PMID:22896614)
• we demonstrate that PI4KIIIalpha activity affects the NS5A phosphorylation status. (PMID:23675303)
• Descriptive Statement The genetic interactions associated with ILVatrophy rate in this study may be mapping variants inSYNJ2andPI4KAthat interact to decrease synthesisof PIP. (PMID:24077433)
• PI4KA mRNA could be used as a new molecular marker to improve established prognostic models for hepatocellular carcinoma. (PMID:24393405)
• PI4KA is essential for the maintenance of plasma membrane phosphatidylinositol 4,5-bisphosphate pools but only during strong stimulation of receptors coupled to phospholipase C activation. (PMID:24415756)
• These results suggest that type II PtdIns 4-kinases are part of piperine-mediated anti-inflammatory signaling mechanisms (PMID:24671493)
• The N-terminal 1,152 amino acids were dispensable for hepatitis C virus replication, phosphatidylinositol 4-phosphate induction, and enzymatic function, thereby defining the minimal PI4KIIIalpha core enzyme at a size of ca. 108 kDa. (PMID:24920820)
• our results suggest a mechanism of PI4K IIalpha recruitment, regulation, and function at the membrane. (PMID:25168678)
• PI4KA and GRM3 polymorphisms have potential to jointly modulate antipsychotic response (PMID:25209194)
• Our results suggest a plasticity of the molecular interactions that control PI4KIIIalpha localization and functions at the plasma membrane. (PMID:25608530)
• Missense mutations in PI4KA are associated with perisylvian polymicrogyria, cerebellar hypoplasia and arthrogryposis. (PMID:25855803)
• PI4K III alpha plays a role in biosynthetic trafficking of two different classes of proteins from the ER to the Golgi complex. (PMID:25886792)
• The results showed that, in contrast to the enteroviruses and the cardioviruses, foot-and-mouth disease virus replication does not require PI4KIII (PI4KIIIalpha and PI4KIIIbeta), and phosphatidylinositol 4-phosphate levels do not increase in foot-and-mouth disease virus-infected cells and phosphatidylinositol 4-phosphate is not seen at replication organelles. (PMID:27093462)
• 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)
• hCKalpha functions as an indispensable regulator that bridges PI4KIIIalpha and hepatitis C virus NS5A and potentiates NS5A-stimulated PI4KIIIalpha activity, which then facilitates the targeting of the ternary complex to the endoplasmic reticulum for viral replication. (PMID:28566381)
• Architecture of the human PI4KIIIalpha lipid kinase complex. (PMID:29229838)
• we provide evidence linking PI4KAP2, previously considered a pseudogene, to human myeloid and erythroid leukemia. (PMID:29386109)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	pi4kab	ENSDARG00000062823
danio_rerio	pi4kaa	ENSDARG00000076724
danio_rerio		ENSDARG00000114976
danio_rerio		ENSDARG00000116796
mus_musculus	Pi4ka	ENSMUSG00000041720
rattus_norvegicus	Pi4ka	ENSRNOG00000060045
drosophila_melanogaster	Pi4KIIIalpha	FBGN0267350
caenorhabditis_elegans		WBGENE00013557

Paralogs (9): PIK3C2A (ENSG00000011405), PIK3CB (ENSG00000051382), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3CA (ENSG00000121879), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PI4KB (ENSG00000143393), PIK3CD (ENSG00000171608)

Protein

Protein identifiers

Phosphatidylinositol 4-kinase alpha — P42356 (reviewed: P42356)

Alternative names: Phosphatidylinositol 4-Kinase III alpha

All UniProt accessions (3): P42356, A8MTF1, C9JLI1

UniProt curated annotations — full annotation on UniProt →

Function. Acts on phosphatidylinositol (PtdIns) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate.

Subunit / interactions. Component of a phosphatidylinositol 4-kinase (PI4K) complex, composed of PI4KA, EFR3 (EFR3A or EFR3B), TTC7 (TTC7A or TTC7B) and HYCC (HYCC1 or HYCC2). Interacts with TMEM150A; regulating recruitment to the plasma membrane. Interacts with TTC7A. (Microbial infection) Interacts with CHKA/Choline Kinase-alpha; CHKA bridges PI4KA and hepatitis C virus (HCV) non-structural protein 5A (NS5A) and potentiates NS5A-stimulated PI4KA activity, which then facilitates the targeting of the ternary complex to the ER for viral replication.

Subcellular location. Cytoplasm. Cell membrane.

Tissue specificity. Expressed ubiquitously. Highest levels in placenta and brain. Little or no expression in lung, liver, pancreas, testis or leukocytes.

Disease relevance. Neurodevelopmental disorder with spasticity, hypomyelinating leukodystrophy, and brain abnormalities (NEDSPLB) [MIM:616531] A severe autosomal recessive disorder characterized by global developmental delay with impaired intellectual development and poor or absent speech, axial hypotonia, and peripheral spasticity and hyperreflexia. Brain imaging shows hypomyelination with decreased white matter volume, cerebral and cerebellar atrophy, and thin corpus callosum. Polymicrogyria may be observed in rare cases. Some patients have a primary immunodeficiency or gastrointestinal disturbances similar to inflammatory bowel disease. The disease is caused by variants affecting the gene represented in this entry. Gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2) [MIM:619708] A severe autosomal recessive disorder characterized by multiple intestinal atresia apparent soon after birth. Affected infants have a distended abdomen, bowel obstruction and do not pass meconium. There is some evidence of inflammatory bowel disease. Death occurs in the first weeks of life. Some patients may also have immunodeficiency. The disease is caused by variants affecting the gene represented in this entry. Spastic paraplegia 84, autosomal recessive (SPG84) [MIM:619621] A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG84 is characterized by onset of slowly progressive walking difficulties due to lower limb weakness, stiffness, and spasticity in the first 2 decades of life. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Activated by Triton X-100, insensitive to inhibition by adenosine and inhibited by wortmannin. Isoform 2 is activated by detergents such as Triton X-100 and inhibited by adenosine. The PI4K complex acts as a regulator of phosphatidylinositol 4-phosphate (PtdIns(4)P) synthesis. Interaction with TMEM150A regulates PtdIns(4)P synthesis.

Similarity. Belongs to the PI3/PI4-kinase family. Type III PI4K subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
P42356-1	1, PI4K230	yes
P42356-2	2, PI4K97

RefSeq proteins (3): NP_001349791, NP_001349792, NP_477352* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR001263	PI3K_accessory_dom	Domain
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015433	PI3/4_kinase	Family
IPR016024	ARM-type_fold	Homologous_superfamily
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR042236	PI3K_accessory_sf	Homologous_superfamily
IPR045495	PI4K_N	Domain

Pfam: PF00454, PF00613, PF19274

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ADP + H(+) (RHEA:19877)

UniProt features (169 total): helix 92, sequence variant 25, strand 23, modified residue 10, turn 9, region of interest 3, domain 2, sequence conflict 2, chain 1, splice variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
9B9G	ELECTRON MICROSCOPY	3.5
9OT6	ELECTRON MICROSCOPY	3.54
6BQ1	ELECTRON MICROSCOPY	3.6
9BAX	ELECTRON MICROSCOPY	3.65

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42356-F1	80.42	0.35

Antibody-complex structures (SAbDab): 1 — 9OT6

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 (10): 260, 262, 265, 429, 1154, 1436, 230, 256, 257, 259

Mutagenesis-validated functional residues (1):

Position	Phenotype
1957	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-1483248	Synthesis of PIPs at the ER membrane
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane

MSigDB gene sets: 482 (showing top): GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, HSIAO_HOUSEKEEPING_GENES, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_HOST_MEDIATED_PERTURBATION_OF_VIRAL_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, HOWLIN_PUBERTAL_MAMMARY_GLAND, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, GOCC_GOLGI_ASSOCIATED_VESICLE, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (7): phosphatidylinositol biosynthetic process (GO:0006661), signal transduction (GO:0007165), host-mediated perturbation of viral process (GO:0044788), phosphatidylinositol phosphate biosynthetic process (GO:0046854), phosphatidylinositol-mediated signaling (GO:0048015), reorganization of cellular membranes to establish viral sites of replication (GO:0140754), lipid metabolic process (GO:0006629)

GO Molecular Function (7): 1-phosphatidylinositol 4-kinase activity (GO:0004430), ATP binding (GO:0005524), cadherin binding (GO:0045296), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), membrane (GO:0016020), Golgi-associated vesicle membrane (GO:0030660), extracellular exosome (GO:0070062)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	2

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
biosynthetic process	1
phosphatidylinositol metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
host-mediated perturbation of symbiont process	1
glycerophospholipid biosynthetic process	1
intracellular signal transduction	1
symbiont-mediated perturbation of host membrane	1
primary metabolic process	1
phosphatidylinositol kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cell adhesion molecule binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
cell periphery	1
cell-substrate junction	1
Golgi-associated vesicle	1
cytoplasmic vesicle membrane	1
bounding membrane of organelle	1
extracellular vesicle	1

Protein interactions and networks

STRING

1572 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PI4KA	PI4K2B	Q8TCG2	764
PI4KA	EFR3A	Q14156	762
PI4KA	PI4K2A	Q9BTU6	761
PI4KA	TTC7A	Q9ULT0	731
PI4KA	EFR3B	Q9Y2G0	713
PI4KA	OSBP	P22059	709
PI4KA	THAP7	Q9BT49	677
PI4KA	SNAP29	O95721	667
PI4KA	HYCC1	Q9BYI3	645
PI4KA	LZTR1	Q8N653	626
PI4KA	TTC7B	Q86TV6	621
PI4KA	PPIA	P05092	620
PI4KA	SYNJ2	O15056	588
PI4KA	VAPA	Q9P0L0	586
PI4KA	SERPIND1	P05546	578

IntAct

183 interactions, top by confidence:

A	B	Type	Score
MED4	MED19	psi-mi:“MI:0914”(association)	0.900
SMARCB1	ARID1A	psi-mi:“MI:0914”(association)	0.860
MED20	MED19	psi-mi:“MI:0914”(association)	0.840
	PI4KA	psi-mi:“MI:0914”(association)	0.730
	PI4KA	psi-mi:“MI:0915”(physical association)	0.730
PI4KA		psi-mi:“MI:0403”(colocalization)	0.730
	PI4KA	psi-mi:“MI:0403”(colocalization)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
	PI4KA	psi-mi:“MI:0914”(association)	0.700
	PI4KA	psi-mi:“MI:0915”(physical association)	0.700
	PI4KA	psi-mi:“MI:0403”(colocalization)	0.700
PI4KA		psi-mi:“MI:0915”(physical association)	0.700
PKN3	ARHGAP10	psi-mi:“MI:0914”(association)	0.680
KLK5	DENND11	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
YWHAH	BLTP3B	psi-mi:“MI:2364”(proximity)	0.570
MTNR1B	IRS4	psi-mi:“MI:0914”(association)	0.530
FAM174A	BLTP3B	psi-mi:“MI:0914”(association)	0.530
NPY2R	RTL8C	psi-mi:“MI:0914”(association)	0.530
CD83	BTAF1	psi-mi:“MI:0914”(association)	0.530
ARRDC4	WWP2	psi-mi:“MI:0914”(association)	0.530

ESM2 similar proteins: A0A0R4I9Y1, A0A0R4IBK5, A2AN08, A2ARZ3, A5WUT8, A6NKT7, B1WBT0, B8RJM0, C9JQI7, E9Q3L2, E9Q555, H2QII6, O08662, O14715, O15050, O43310, O75592, O75969, P0DJD0, P0DJD1, P13864, P42356, P49792, Q0V9S3, Q0VF22, Q24K09, Q2TL32, Q4R6W9, Q4V847, Q63HN8, Q6PB60, Q6PEE2, Q71HP2, Q7TPH6, Q7TPV2, Q7Z3J3, Q80930, Q80TA9, Q810N5, Q811D2

Diamond homologs: A4IID4, A4QPH2, A9X1A0, B0KWC1, B1MTG7, B2KI64, B3EX61, B4UT09, E9Q3L2, G5EDY0, O02697, O02810, O02811, O08561, O08662, O14356, O70167, O70173, O75747, P0CP60, P0CP61, P37297, P39104, P42338, P42347, P42348, P42356, P48736, P50520, P54677, Q0WPX9, Q10366, Q49GP3, Q6GN16, Q8BKC8, Q8BTI9, Q8SQY7, Q9C680, Q9FMJ0, Q9JHG7

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
EFR3A	“up-regulates quantity”	PI4KA	binding
EFR3B	“up-regulates quantity”	PI4KA	binding
PI4KA	“down-regulates quantity”	1-phosphatidyl-1D-myo-inositol(1-)	“chemical modification”
PI4KA	“down-regulates quantity”	ATP(4-)	“chemical modification”
PI4KA	“up-regulates quantity”	“1-phosphatidyl-1D-myo-inositol 4-phosphate”	“chemical modification”
PI4KA	“up-regulates quantity”	ADP(3-)	“chemical modification”

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — PLMESO.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	26
Uncertain significance	214
Likely benign	96
Benign	126

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1034208	NM_058004.4(PI4KA):c.3275C>A (p.Ser1092Ter)	Pathogenic
1325871	NM_058004.4(PI4KA):c.2624dup (p.Pro876fs)	Pathogenic
1325873	NM_058004.4(PI4KA):c.3592G>A (p.Ala1198Thr)	Pathogenic
1325874	NM_058004.4(PI4KA):c.6156_6159del (p.Thr2053fs)	Pathogenic
1325875	NM_058004.4(PI4KA):c.5456AAG[1] (p.Glu1820del)	Pathogenic
1325877	NM_058004.4(PI4KA):c.5159C>T (p.Thr1720Ile)	Pathogenic
1335865	NM_058004.4(PI4KA):c.4867T>G (p.Tyr1623Asp)	Pathogenic
1335866	NM_058004.4(PI4KA):c.5774G>A (p.Gly1925Glu)	Pathogenic
1335867	NM_058004.4(PI4KA):c.6065del (p.Arg2022fs)	Pathogenic
1335868	NM_058004.4(PI4KA):c.2330T>C (p.Leu777Pro)	Pathogenic
1335869	NM_058004.4(PI4KA):c.3571C>T (p.Gln1191Ter)	Pathogenic
14953	NM_000185.4(SERPIND1):c.321dup (p.Val108fs)	Pathogenic
14954	NM_000185.4(SERPIND1):c.1429_1430del (p.Phe477fs)	Pathogenic
14955	NM_000185.4(SERPIND1):c.1385C>T (p.Pro462Leu)	Pathogenic
1686063	NM_058004.4(PI4KA):c.2575-1G>A	Pathogenic
1879567	GRCh37/hg19 22q11.21(chr22:18894078-21414817)x1	Pathogenic
208450	NM_058004.4(PI4KA):c.2386C>T (p.Arg796Ter)	Pathogenic
2175799	NM_058004.4(PI4KA):c.2624del (p.Pro875fs)	Pathogenic
2581427	NM_058004.4(PI4KA):c.2977del (p.Leu993fs)	Pathogenic
2583000	NM_058004.4(PI4KA):c.1080del (p.Ser361fs)	Pathogenic
4086004	GRCh37/hg19 22q11.21(chr22:21064987-21065146)x1	Pathogenic
4848356	NM_058004.4(PI4KA):c.591C>G (p.Tyr197Ter)	Pathogenic
1325872	NM_058004.4(PI4KA):c.3454G>A (p.Glu1152Lys)	Likely pathogenic
1675874	NM_058004.4(PI4KA):c.5974C>T (p.Pro1992Ser)	Likely pathogenic
1676320	NM_058004.4(PI4KA):c.1852C>T (p.Arg618Ter)	Likely pathogenic
1710377	NM_058004.4(PI4KA):c.2751del (p.Cys918fs)	Likely pathogenic
1723895	NM_058004.4(PI4KA):c.4901del (p.Thr1634fs)	Likely pathogenic
1804845	NM_058004.4(PI4KA):c.1687G>T (p.Glu563Ter)	Likely pathogenic
208451	NM_058004.4(PI4KA):c.5560G>A (p.Asp1854Asn)	Likely pathogenic
2572113	NM_000185.4(SERPIND1):c.1147A>T (p.Lys383Ter)	Likely pathogenic

SpliceAI

10890 predictions. Top by Δscore:

Variant	Effect	Δscore
22:20709294:A:AC	donor_gain	1.0000
22:20709295:C:CC	donor_gain	1.0000
22:20709377:TGC:T	acceptor_gain	1.0000
22:20709901:AACCT:A	donor_loss	1.0000
22:20709902:ACCTA:A	donor_loss	1.0000
22:20709903:CCTAC:C	donor_loss	1.0000
22:20709904:CTA:C	donor_loss	1.0000
22:20709905:TA:T	donor_loss	1.0000
22:20709906:A:AC	donor_gain	1.0000
22:20709906:ACT:A	donor_loss	1.0000
22:20709907:C:CC	donor_gain	1.0000
22:20709907:CTT:C	donor_gain	1.0000
22:20709909:T:TA	donor_gain	1.0000
22:20709995:GGCCT:G	acceptor_loss	1.0000
22:20709997:CCTG:C	acceptor_loss	1.0000
22:20709998:C:CA	acceptor_loss	1.0000
22:20709999:T:C	acceptor_loss	1.0000
22:20710737:C:CT	donor_gain	1.0000
22:20711339:A:AC	donor_gain	1.0000
22:20711340:C:CC	donor_gain	1.0000
22:20711354:ATGAC:A	donor_gain	1.0000
22:20711362:T:TA	donor_gain	1.0000
22:20712510:AT:A	donor_gain	1.0000
22:20712510:ATC:A	donor_gain	1.0000
22:20712510:ATCC:A	donor_gain	1.0000
22:20712511:T:C	donor_gain	1.0000
22:20712518:A:AC	donor_gain	1.0000
22:20712519:C:CC	donor_gain	1.0000
22:20712607:CCGCA:C	acceptor_gain	1.0000
22:20712608:CGCA:C	acceptor_gain	1.0000

AlphaMissense

13866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:20708066:T:G	Q2097P	1.000
22:20708074:C:A	Q2094H	1.000
22:20708074:C:G	Q2094H	1.000
22:20708084:T:A	D2091V	1.000
22:20708084:T:G	D2091A	1.000
22:20708085:C:G	D2091H	1.000
22:20708088:A:C	Y2090D	1.000
22:20708088:A:G	Y2090H	1.000
22:20709373:C:A	R2060S	1.000
22:20709373:C:G	R2060S	1.000
22:20709374:C:A	R2060M	1.000
22:20709374:C:G	R2060T	1.000
22:20709911:A:G	L2057S	1.000
22:20709934:A:C	F2049L	1.000
22:20709934:A:T	F2049L	1.000
22:20709935:A:G	F2049S	1.000
22:20709936:A:G	F2049L	1.000
22:20709937:A:C	C2048W	1.000
22:20709938:C:T	C2048Y	1.000
22:20709939:A:G	C2048R	1.000
22:20709944:A:G	L2046P	1.000
22:20709958:C:A	M2041I	1.000
22:20709958:C:G	M2041I	1.000
22:20709958:C:T	M2041I	1.000
22:20709968:A:T	V2038D	1.000
22:20710715:C:G	G2023R	1.000
22:20710786:T:A	E1999V	1.000
22:20710795:A:G	L1996P	1.000
22:20710797:C:A	K1995N	1.000
22:20710797:C:G	K1995N	1.000

dbSNP variants (sampled 300 via entrez): RS1000027408 (22:20781284 T>C), RS1000030082 (22:20757355 A>C), RS1000095035 (22:20796409 G>A,C), RS1000101665 (22:20788975 C>G), RS1000107017 (22:20714192 A>G), RS1000135993 (22:20856052 C>T), RS1000140887 (22:20810683 A>G), RS1000153869 (22:20729679 G>A), RS1000156785 (22:20826425 C>A,T), RS1000190189 (22:20855779 T>C), RS1000198760 (22:20774923 A>C), RS1000203013 (22:20734005 A>C,T), RS1000228989 (22:20814092 C>G,T), RS1000253180 (22:20763931 T>C), RS1000253905 (22:20858179 T>G)

Disease associations

OMIM: gene MIM:600286 | disease phenotypes: MIM:616531, MIM:619621, MIM:619708, MIM:612356, MIM:261600, MIM:191100, MIM:609528

GenCC curated gene-disease

Disease	Classification	Inheritance
polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis	Definitive	Autosomal recessive

Mondo (9): polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (MONDO:0014679), PI4KA-related disorder (MONDO:1040012), spastic paraplegia 84, autosomal recessive (MONDO:0030482), gastrointestinal defects and immunodeficiency syndrome 2 (MONDO:0030669), heparin cofactor 2 deficiency (MONDO:0012876), phenylketonuria (MONDO:0009861), long QT syndrome (MONDO:0002442), tuberous sclerosis 1 (MONDO:0008612), CEDNIK syndrome (MONDO:0012290)

Orphanet (4): Autosomal recessive spastic paraplegia type 84 (Orphanet:631079), Phenylketonuria (Orphanet:716), Tuberous sclerosis complex (Orphanet:805), CEDNIK syndrome (Orphanet:66631)

HPO phenotypes

140 total (30 of 140 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000012	Urinary urgency
HP:0000143	Rectovaginal fistula
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0000453	Choanal atresia
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000750	Delayed speech and language development
HP:0000767	Pectus excavatum
HP:0000778	Hypoplasia of the thymus
HP:0000872	Hashimoto thyroiditis
HP:0001072	Thickened skin
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001257	Spasticity
HP:0001258	Spastic paraplegia
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001272	Cerebellar atrophy
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001310	Dysmetria
HP:0001320	Cerebellar vermis hypoplasia
HP:0001321	Cerebellar hypoplasia
HP:0001328	Specific learning disability
HP:0001332	Dystonia

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007433_8	Fulminant type 1 diabetes	7.000000e-06
GCST009391_1107	Metabolite levels	2.000000e-06
GCST90002394_206	Monocyte percentage of white cells	2.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0010448	3-hydroxyphenylacetic acid measurement
EFO:0007989	monocyte percentage of leukocytes

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D010661	Phenylketonurias	C10.228.140.163.100.687; C16.320.565.100.766; C16.320.565.189.687; C18.452.132.100.687; C18.452.648.100.766; C18.452.648.189.687
C537943	Cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma syndrome (supp.)
C562865	Heparin Cofactor II Deficiency (supp.)
C565346	Tuberous Sclerosis 1 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2096619 (PROTEIN FAMILY), CHEMBL3038509 (PROTEIN COMPLEX), CHEMBL3667 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 222,014 (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
CHEMBL477	ADENOSINE	4	222,014

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs165854	PI4KA		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1-phosphatidylinositol 4-kinase family

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
wortmannin	Inhibition	6.8	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
STK16-IN-1	IC50	7940 nM

ChEMBL bioactivities

102 potent at pChembl≥5 of 184 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.50	IC50	0.3162	nM	CHEMBL3121323
9.10	IC50	0.7943	nM	CHEMBL3121314
9.00	IC50	1	nM	CHEMBL3121322
9.00	IC50	1	nM	CHEMBL3121319
9.00	IC50	1	nM	CHEMBL3600785
8.80	IC50	1.585	nM	CHEMBL3121334
8.80	IC50	1.585	nM	CHEMBL3121327
8.70	IC50	1.995	nM	CHEMBL3600784
8.60	IC50	2.512	nM	CHEMBL3121318
8.40	IC50	3.981	nM	CHEMBL3121320
8.30	IC50	5.012	nM	CHEMBL3121308
8.30	IC50	5.012	nM	CHEMBL3121333
8.30	IC50	5.012	nM	CHEMBL3600781
8.20	IC50	6.31	nM	CHEMBL3121324
8.20	IC50	6.31	nM	CHEMBL3600779
8.10	IC50	7.943	nM	CHEMBL3600782
8.00	IC50	10	nM	CHEMBL3121311
8.00	IC50	10	nM	CHEMBL3121326
7.80	IC50	15.85	nM	CHEMBL3121308
7.80	IC50	15.85	nM	CHEMBL3121321
7.70	IC50	19.95	nM	CHEMBL3121316
7.50	IC50	31.62	nM	CHEMBL3121312
7.40	IC50	39.81	nM	CHEMBL3121325
7.40	IC50	39.81	nM	CHEMBL3121328
7.40	IC50	39.81	nM	CHEMBL3600783
7.30	IC50	50.12	nM	CHEMBL3121310
7.30	IC50	50.12	nM	CHEMBL3121309
7.10	IC50	79.43	nM	CHEMBL3600687
7.00	IC50	100	nM	CHEMBL3121329
7.00	IC50	100	nM	CHEMBL3600684
6.90	IC50	125.9	nM	CHEMBL3121308
6.90	IC50	125.9	nM	CHEMBL3121317
6.88	IC50	130.6	nM	CHEMBL4161766
6.80	IC50	158.5	nM	CHEMBL3600776
6.80	IC50	158.5	nM	CHEMBL3600683
6.79	IC50	163.7	nM	CHEMBL4164334
6.78	IC50	165	nM	CHEMBL4752128
6.70	IC50	199.5	nM	CHEMBL3121331
6.55	IC50	280	nM	WORTMANNIN
6.50	IC50	316.2	nM	CHEMBL3121313
6.50	IC50	316.2	nM	CHEMBL3600778
6.50	IC50	316.2	nM	CHEMBL3600767
6.50	IC50	316.2	nM	CHEMBL3600695
6.50	IC50	316.2	nM	CHEMBL3600694
6.40	IC50	398.1	nM	CHEMBL3600699
6.35	IC50	450	nM	CHEMBL3901551
6.30	IC50	501.2	nM	CHEMBL3600777
6.26	IC50	553	nM	CHEMBL3947384
6.24	IC50	574.1	nM	CHEMBL4174988
6.20	IC50	631	nM	CHEMBL3121330

PubChem BioAssay actives

99 with measured affinity, of 400 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-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]pyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0003	uM
N-[2-amino-5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0008	uM
4-[[[6-[1-(cyclopropylmethyl)-2-oxo-4-pyridinyl]-1,3-benzothiazol-2-yl]amino]methyl]cyclohexane-1-carboxylic acid	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0010	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]-2-methylbenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0010	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]-4-cyanobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0010	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0016	uM
2,4-difluoro-N-[2-methoxy-5-(4-morpholin-4-ylquinazolin-6-yl)-3-pyridinyl]benzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0016	uM
1-(cyclopropylmethyl)-4-[2-[(1,1-dioxothian-4-yl)methylamino]-1,3-benzothiazol-6-yl]pyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0020	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]benzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0025	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]-3-methylbenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0040	uM
1-(cyclopropylmethyl)-4-[2-(oxan-4-ylmethylamino)-1,3-benzothiazol-6-yl]pyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0050	uM
5-[2-amino-4-oxo-3-[2-(trifluoromethyl)phenyl]quinazolin-6-yl]-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0050	uM
N-[5-(2-amino-3-phenylquinoxalin-6-yl)-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0050	uM
5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0063	uM
4-(2-amino-1,3-benzothiazol-6-yl)-1-(cyclopropylmethyl)pyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0063	uM
1-(cyclopropylmethyl)-4-[2-[[(1R)-1-(oxan-4-yl)ethyl]amino]-1,3-benzothiazol-6-yl]pyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0079	uM
5-[2-amino-3-(2-methylphenyl)-4-oxoquinazolin-6-yl]-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0100	uM
5-[2-amino-3-(oxan-4-yl)-4-oxoquinazolin-6-yl]-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0100	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]-4-methylbenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0158	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]methanesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0199	uM
5-[2-amino-4-oxo-3-(2-propan-2-ylphenyl)quinazolin-6-yl]-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0316	uM
1-(cyclopropylmethyl)-4-[2-[[(1S)-1-(oxan-4-yl)ethyl]amino]-1,3-benzothiazol-6-yl]pyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0398	uM
N-[5-[2-amino-3-(4-morpholin-4-ylphenyl)quinolin-6-yl]-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0398	uM
5-(2-amino-3-ethyl-4-oxoquinazolin-6-yl)-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0398	uM
5-[2-amino-4-oxo-3-[4-(trifluoromethyl)phenyl]quinazolin-6-yl]-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0501	uM
5-[2-amino-4-oxo-3-[3-(trifluoromethyl)phenyl]quinazolin-6-yl]-N-(2,4-difluorophenyl)-2-methoxypyridine-3-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.0501	uM
6-(6-propan-2-yloxy-3-pyridinyl)-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.0794	uM
6-(6-ethylsulfanyl-3-pyridinyl)-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.1000	uM
N-[5-(2-amino-3-phenylquinolin-6-yl)-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.1000	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxy-3-pyridinyl]propane-2-sulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.1259	uM
(2S)-2-amino-N-[5-[6-chloro-5-[(2-methylphenyl)sulfonylamino]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide	1361703: Inhibition of PI4K3A (unknown origin) using PI:PS as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr in presence of 50 uM ATP by ADP-Glo luminescence assay	ic50	0.1306	uM
6-(6-ethoxy-3-pyridinyl)-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.1585	uM
6-(1-benzylpyrazol-4-yl)-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.1585	uM
(2S)-2-amino-N-[5-[6-chloro-5-[(4-methylphenyl)sulfonylamino]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide	1361703: Inhibition of PI4K3A (unknown origin) using PI:PS as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr in presence of 50 uM ATP by ADP-Glo luminescence assay	ic50	0.1637	uM
5-[5-(benzenesulfonamido)-6-chloro-3-pyridinyl]-N-methylpyridine-3-carboxamide	1688362: Inhibition of human PI4K3alpha by ADP-Glo kinase assay	ic50	0.1650	uM
N-[5-(2-amino-3-phenyl-1,7-naphthyridin-6-yl)-2-methoxy-3-pyridinyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.1995	uM
[(1R,3R,5S,9R,18S)-18-(methoxymethyl)-1,5-dimethyl-6,11,16-trioxo-13,17-dioxapentacyclo[10.6.1.02,10.05,9.015,19]nonadeca-2(10),12(19),14-trien-3-yl] acetate	1917568: Inhibition of PI4KA catalytic domain (unknown origin) assessed as enzyme residual activity incubated for 60 mins using ATP as substrate by ATP-Glo luminescent assay	ic50	0.2800	uM
2-[[5-(2-amino-1,3-benzothiazol-6-yl)-2-pyridinyl]oxy]ethanol	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.3162	uM
6-[6-(2-methoxyethoxy)-3-pyridinyl]-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.3162	uM
4-(2-amino-1,3-benzothiazol-6-yl)-1H-pyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.3162	uM
4-(2-amino-1,3-benzothiazol-6-yl)-1-ethylpyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.3162	uM
N-[5-(2-amino-4-oxo-3-phenylquinazolin-6-yl)-2-methoxyphenyl]-2,4-difluorobenzenesulfonamide	1070712: Inhibition of GST-tagged PI4K-alpha (1 to 2044) (unknown origin) using D-myo-phosphatidylinositol as substrate preincubated for 30 mins followed by substrate addition measured after 180 mins by luminescence assay	ic50	0.3162	uM
6-(5-methylsulfonyl-3-pyridinyl)-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.3981	uM
tert-butyl 3-[[8-(2-chlorophenyl)-4,5-dihydro-[1,3]thiazolo[4,5-h]quinazolin-2-yl]carbamoylamino]propanoate	1324668: Inhibition of N-terminal GST-tagged PI4KA (875 to 2044 residues) (unknown origin) expressed in Sf21 cells using soluble lipid PI-diC8 by fluorescence polarization assay	ic50	0.4500	uM
4-(2-amino-1,3-benzothiazol-6-yl)-1-methylpyridin-2-one	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.5012	uM
N-(4-aminocyclohexyl)-5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxybenzenesulfonamide	1324672: Inhibition of PI4KA (unknown origin) by ADP-Glo kinase assay	ic50	0.5530	uM
(2S)-2-amino-N-[5-[6-chloro-5-[(3-methylphenyl)sulfonylamino]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]-3-methylbutanamide	1361703: Inhibition of PI4K3A (unknown origin) using PI:PS as substrate preincubated for 1 hr followed by substrate addition and measured after 1 hr in presence of 50 uM ATP by ADP-Glo luminescence assay	ic50	0.5741	uM
6-[6-(ethylamino)-3-pyridinyl]-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.6310	uM
6-[6-[ethyl(methyl)amino]-3-pyridinyl]-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.6310	uM
6-[1-(cyclopropylmethyl)pyrazol-4-yl]-1,3-benzothiazol-2-amine	1238222: Inhibition of N-terminal FLAG-tagged human full length recombinant PI4K3alpha using D-myo-phosphatidylinositol substrate and ATP incubated for 45 mins by ADP-Glo kinase Assay	ic50	0.6310	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, affects cotreatment, decreases methylation	2
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	decreases expression, decreases response to substance	2
Quercetin	increases expression, increases phosphorylation	2
Valproic Acid	increases expression, increases methylation	2
bisphenol F	affects cotreatment, decreases expression	1
2,4,6-tribromophenol	decreases expression	1
arsenite	affects binding, decreases reaction	1
o,p’-DDT	increases activity	1
tetrabromobisphenol A	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
coumarin	affects phosphorylation	1
butylparaben	increases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
rofecoxib	decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation, increases methylation	1
Microplastics	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Catechin	decreases expression, affects cotreatment	1
Cycloheximide	increases reaction, decreases expression	1

ChEMBL screening assays

86 unique, capped per target: 83 binding, 2 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL758625	Binding	Inhibition of Phosphatidylinositol 4-kinase of human epidermoid carcinoma A431 cells	Synthesis of echiguanine analogs and their ribofuranosyl glycosides that inhibit phosphatidylinositol 4-kinase — Bioorg Med Chem Lett
CHEMBL760329	Functional	Rate of phosphorylation was determined with that of mammalian PI using human erythrocyte PI 4-kinase at 200 uM substrate	Total synthesis of the four stereoisomers of dihexadecanoyl phosphatidylinositol and the substrate stereospecificity of human erythrocyte membrane phosphatidylinositol 4-kinase. — J Med Chem
CHEMBL4683372	ADMET	Inhibition of human PI4K3alpha by ADP-Glo kinase assay	Discovery of 6’-chloro-N-methyl-5’-(phenylsulfonamido)-[3,3’-bipyridine]-5-carboxamide (CHMFL-PI4K-127) as a novel Plasmodium falciparum PI(4)K inhibitor with potent antimalarial activity against both blood and liver stages of Plasmodium. — Eur J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01082328	PHASE4	COMPLETED	Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
NCT01617070	PHASE4	COMPLETED	Effects of Kuvan on Melatonin Secretion
NCT01965912	PHASE4	COMPLETED	Kuvan®’s Effect on the Cognition of Children With Phenylketonuria
NCT02677870	PHASE4	COMPLETED	The Effectiveness of Kuvan in Amish PKU Patients
NCT03788343	PHASE4	COMPLETED	Phenylalanine and Its Impact on Cognition
NCT04227080	PHASE4	UNKNOWN	BH4 Responsiveness in PAH Deficiency PKU Patients
NCT06780332	PHASE4	ACTIVE_NOT_RECRUITING	Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to Palynziq
NCT06901323	PHASE4	ACTIVE_NOT_RECRUITING	Effect of L-carnitine Supplementation on Phenylalanine and Brain-derived Neurotrophic Factor Levels in Infants and Children With Phenylketonuria
NCT07477691	PHASE4	NOT_YET_RECRUITING	Immune Modulation During Palynziq® Treatment in Adults (IMPALA)
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00104247	PHASE3	COMPLETED	Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels
NCT00225615	PHASE3	COMPLETED	A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With PKU Who Have Elevated Phenylalanine Levels
NCT00272792	PHASE3	COMPLETED	Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet
NCT00332189	PHASE3	COMPLETED	Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
NCT00838435	PHASE3	COMPLETED	Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
NCT01114737	PHASE3	COMPLETED	Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients
NCT01376908	PHASE3	COMPLETED	Kuvan® in Phenylketonuria Patients Less Than 4 Years Old
NCT01732471	PHASE3	COMPLETED	Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
NCT01819727	PHASE3	COMPLETED	An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165
NCT01889862	PHASE3	COMPLETED	Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU
NCT03694353	PHASE3	COMPLETED	Safety and Efficacy of Self Administered Injections of Pegvaliase (>40mg/Day Dose) in Adults With PKU
NCT05099640	PHASE3	COMPLETED	A Study of PTC923 in Participants With Phenylketonuria
NCT05166161	PHASE3	ACTIVE_NOT_RECRUITING	A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
NCT05270837	PHASE3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria
NCT05764239	PHASE3	TERMINATED	Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)
NCT06302348	PHASE3	RECRUITING	A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
NCT06628128	PHASE3	RECRUITING	A Long-Term Study of JNT-517 in Participants With Phenylketonuria
NCT06971731	PHASE3	RECRUITING	A Study of JNT-517 in Participants With Phenylketonuria (PKU)
NCT00104260	PHASE2	COMPLETED	Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptin™ Treatment in Subjects With Phenylketonuria
NCT00260000	PHASE2	COMPLETED	Study of BH4, a New and Simple Treatment of Mild PKU
NCT00841100	PHASE2	COMPLETED	Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response
NCT00924703	PHASE2	COMPLETED	Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003)
NCT00925054	PHASE2	COMPLETED	Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU
NCT01212744	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy Study of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PKU)
NCT01395394	PHASE2	TERMINATED	Phenylketonuria, Oxidative Stress, and BH4
NCT01560286	PHASE2	COMPLETED	A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks
NCT01977820	PHASE2	TERMINATED	Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria