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): 639 total — 24 pathogenic, 31 likely-pathogenic (top 5% of genes corpus-wide)
• Regional missense constraint (gnomAD): 5 of 13 regions constrained (≈17% of expected missense variation)
• GTEx eGene: eQTL in 39 tissues, sQTL in 30 (q < 0.05)
• Phenotypes (HPO): 140
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types (inferred from mutation patterns)
• Cancer dependency (DepMap): dependent in 90.0% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.55 (moderately constrained)
• 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: 41 — 21 protein_coding, 13 retained_intron, 5 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000255882

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 7, TSL 3: 2, TSL 4: 3, TSL 5: 4

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, ENST00001057221, ENST00001057223, ENST00001085694, ENST00001085695, ENST00001109047, ENST00001109048, ENST00001116301, ENST00001133405

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.

Highest expression (Bgee): superior frontal gyrus, frontal lobe, Brodmann (1909) area 9, frontal cortex, hemisphere of cerebellum.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PI4KA is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 39 tissues and its splicing (sQTL) in 30 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 69 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	eqtl	2.3e-61	-0.39	22:20777866:C:T
Thyroid	eqtl	2.3e-38	-0.35	22:20712214:T:C
Esophagus Mucosa	eqtl	3.2e-38	-0.29	22:20856731:T:C
Skin Not Sun Exposed Suprapubic	eqtl	2.0e-36	-0.31	22:20748801:C:T
Skin Sun Exposed Lower leg	eqtl	1.2e-35	-0.29	22:20748801:C:T
Pituitary	eqtl	9.7e-34	-0.39	22:20863287:A:G
Testis	sqtl	8.3e-33	-0.90	22:20736827:A:G
Heart Left Ventricle	eqtl	5.3e-32	-0.32	22:20885252:C:G
Heart Atrial Appendage	eqtl	1.9e-29	-0.34	22:20748801:C:T
Thyroid	sqtl	1.7e-25	-1.07	22:21468436:T:C
Artery Aorta	eqtl	4.8e-24	-0.27	22:20797367:A:G
Artery Tibial	eqtl	1.2e-23	-0.19	22:20886905:A:G
Colon Sigmoid	eqtl	1.7e-22	-0.23	22:20836468:G:C
Adipose Subcutaneous	eqtl	3.2e-22	-0.22	22:20712654:G:T
Prostate	eqtl	6.1e-22	-0.40	22:20885252:C:G
Esophagus Muscularis	eqtl	1.1e-21	-0.19	22:20819020:C:T
Testis	eqtl	1.1e-19	-0.23	22:20904004:A:C
Colon Transverse	eqtl	9.2e-18	-0.25	22:20852374:G:A
Adipose Subcutaneous	sqtl	1.8e-16	-0.78	22:21468436:T:C
Spleen	eqtl	2.3e-16	-0.33	22:20846243:A:G

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

showing 100 of 143 tissues 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
embryo	UBERON:0000922	94.84	gold quality
ganglionic eminence	UBERON:0004023	94.84	gold quality
stromal cell of endometrium	CL:0002255	94.80	gold quality
fundus of stomach	UBERON:0001160	94.75	gold quality
endocervix	UBERON:0000458	94.74	gold quality
testis	UBERON:0000473	94.67	gold quality
myometrium	UBERON:0001296	94.61	gold quality
ectocervix	UBERON:0012249	94.58	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.53	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.52	gold quality
lower esophagus	UBERON:0013473	94.49	gold quality
left uterine tube	UBERON:0001303	94.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.47	gold quality
left ovary	UBERON:0002119	94.31	gold quality
right lobe of thyroid gland	UBERON:0001119	94.30	gold quality
uterine cervix	UBERON:0000002	94.29	gold quality
right ovary	UBERON:0002118	94.29	gold quality
bone marrow cell	CL:0002092	94.21	gold quality
substantia nigra	UBERON:0002038	94.19	gold quality
spleen	UBERON:0002106	94.19	gold quality
corpus callosum	UBERON:0002336	94.17	gold quality
prostate gland	UBERON:0002367	94.10	gold quality
bone marrow	UBERON:0002371	94.02	gold quality
left lobe of thyroid gland	UBERON:0001120	94.01	gold quality
bone element	UBERON:0001474	94.01	gold quality
upper lobe of left lung	UBERON:0008952	93.99	gold quality
tibial nerve	UBERON:0001323	93.98	gold quality
thyroid gland	UBERON:0002046	93.96	gold quality
ovary	UBERON:0000992	93.95	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.88	gold quality
blood	UBERON:0000178	93.86	gold quality
mucosa of stomach	UBERON:0001199	93.69	gold quality
body of stomach	UBERON:0001161	93.57	gold quality
anatomical system	UBERON:0000467	93.48	gold quality
material anatomical entity	UBERON:0000465	93.47	gold quality
multicellular organism	UBERON:0000468	93.47	gold quality
small intestine	UBERON:0002108	93.47	gold quality
stomach	UBERON:0000945	93.45	gold quality
colon	UBERON:0001155	93.42	gold quality
intestine	UBERON:0000160	93.27	gold quality
ascending aorta	UBERON:0001496	93.24	gold quality
popliteal artery	UBERON:0002250	93.23	gold quality
aorta	UBERON:0000947	93.22	gold quality
tibial artery	UBERON:0007610	93.21	gold quality
thoracic aorta	UBERON:0001515	93.20	gold quality
vagina	UBERON:0000996	93.17	gold quality
apex of heart	UBERON:0002098	93.12	gold quality
transverse colon	UBERON:0001157	93.10	gold quality
colonic epithelium	UBERON:0000397	93.06	gold quality
urinary bladder	UBERON:0001255	93.03	gold quality
right lung	UBERON:0002167	92.87	gold quality
right adrenal gland	UBERON:0001233	92.85	gold quality
lung	UBERON:0002048	92.75	gold quality
descending thoracic aorta	UBERON:0002345	92.74	gold quality
mucosa of transverse colon	UBERON:0004991	92.74	gold quality
left coronary artery	UBERON:0001626	92.73	gold quality
metanephros cortex	UBERON:0010533	92.71	gold quality
left adrenal gland cortex	UBERON:0035825	92.71	gold quality
left adrenal gland	UBERON:0001234	92.58	gold quality
right coronary artery	UBERON:0001625	92.58	gold quality
adrenal gland	UBERON:0002369	92.58	gold quality
right adrenal gland cortex	UBERON:0035827	92.53	gold quality
omental fat pad	UBERON:0010414	92.46	gold quality
lymph node	UBERON:0000029	92.36	gold quality
right uterine tube	UBERON:0001302	92.34	gold quality
right atrium auricular region	UBERON:0006631	92.29	gold quality
esophagus	UBERON:0001043	92.23	gold quality
adult mammalian kidney	UBERON:0000082	92.18	gold quality
right lobe of liver	UBERON:0001114	92.15	gold quality
ventricular zone	UBERON:0003053	92.14	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Postcentral gyrus	tissue	231.6
Hippocampus	tissue	132.7	not detected
Nucleus accumbens	tissue	121.5
Choroid plexus	tissue	109.9
Locus coeruleus	tissue	106.8
Cerebral cortex	tissue	86.9	medium
Somatosensory cortex	tissue	86.9
Motor cortex	tissue	86.3
Frontal cortex	tissue	85.5
Prefrontal cortex	tissue	84.9
Hippocampal formation	tissue	82.2
Pons	tissue	79.6
Thalamus	tissue	76.9
Occipital cortex	tissue	76.1
Caudate putamen	tissue	75.4
Retrosplenial and cingulate cortex	tissue	75.1
Superior colliculi	tissue	75.0
Insular cortex	tissue	74.3
Temporal cortex	tissue	74.0
Entorhinal cortex	tissue	73.9
Substantia nigra	tissue	72.2
Retrosplenial cortex	tissue	71.9
Midbrain	tissue	66.1
Amygdala	tissue	63.5
Ventral forebrain	tissue	62.9
Basal ganglia	tissue	61.2	not detected
Hypothalamus	tissue	59.9
Putamen	tissue	59.0
Septum	tissue	57.6
Medulla oblongata	tissue	55.6
Spinal cord	tissue	51.3
Cerebellum	tissue	47.7	medium
Periaqueductal gray	tissue	47.2
Olfactory bulb	tissue	46.8
Parathyroid gland	tissue	32.4	low
Thymus	tissue	31.9
Corpus callosum	tissue	27.8
Pituitary gland	tissue	26.0
Retina	tissue	25.6
Bone marrow	tissue	22.7	medium
Testis	tissue	21.3	medium
Smooth muscle	tissue	20.4	not detected
Lymph node	tissue	19.1	medium
Appendix	tissue	18.0	medium
Spleen	tissue	17.4	medium
Placenta	tissue	16.8	medium
Tonsil	tissue	16.8	medium
Vagina	tissue	16.6	not detected
Small intestine	tissue	16.5	not detected
Stomach 1	tissue	16.3	not detected
Seminal vesicle	tissue	15.9	medium
Thyroid gland	tissue	15.6	low
Endometrium 1	tissue	15.1	medium
Duodenum	tissue	14.9	not detected
Prostate	tissue	14.9	not detected
Tongue	tissue	14.8
Lung	tissue	14.7	high
Colon	tissue	14.3	low
Cervix	tissue	14.2	not detected
Rectum	tissue	14.0	not detected

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Perirhinal gyrus (223.0), Superior temporal gyrus (219.8), Olfactory area (218.9), Precentral gyrus (216.7), Olfactory tubercle (212.9).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PI4KA by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 32 miRNAs:

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

gnomAD constraint: pLI 1.95e-06, LOEUF 0.548, missense Z 4.64 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000255882 splits into 13 regions with different missense tolerance; 5 are missense-constrained (≈17% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:20,708,050–20,713,282	110 / 349.8	0.31	yes (p 1.3e-37)
22:20,713,283–20,729,911	388 / 521.5	0.74	no
22:20,729,912–20,729,952	3 / 18.5	0.16	yes (p 3.1e-04)
22:20,729,953–20,730,000	23 / 23.2	0.99	no
22:20,730,001–20,733,039	7 / 33.8	0.21	yes (p 4.0e-06)
22:20,733,040–20,734,094	72 / 103.1	0.70	no
22:20,734,095–20,734,405	11 / 49.6	0.22	yes (p 4.3e-08)
22:20,734,406–20,747,629	203 / 256.8	0.79	no
22:20,747,630–20,747,669	2 / 17.4	0.12	yes (p 2.3e-04)
22:20,747,670–20,798,680	368 / 544.3	0.68	no
22:20,798,681–20,804,355	228 / 261.6	0.87	no
22:20,804,356–20,805,013	14 / 34.0	0.41	no
22:20,805,014–20,858,725	540 / 555.5	0.97	no
DepMap (CRISPR cell-line fitness): dependent in 90.0% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): OV-90 (-2.191), NCI-H747 (-1.746), TUHR10TKB (-1.713), SNU-685 (-1.631), HCC-827-GR5 (-1.595), UACC-893 (-1.592), KLE (-1.571), EM-2 (-1.548), SIHA (-1.519), CADO-ES1 (-1.51), U-178 (-1.504), NCI-H522 (-1.479), J82 (-1.455), RT4 (-1.43), SNU-182 (-1.423).

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

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pi4kaa	ENSDARG00000076724
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:2448506) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 36 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased monocyte cell number	1
abnormal digestive system morphology	1
abnormal intestine morphology	1
abnormal large intestine morphology	1
abnormal cecum morphology	1
abnormal spleen morphology	1
decreased body weight	1
decreased body size	1
unresponsive to tactile stimuli	1
hunched posture	1
abnormal coat appearance	1
limb grasping	1
abnormal digestion	1
premature death	1
increased hematocrit	1
increased erythrocyte cell number	1
abnormal duodenum morphology	1
abnormal gastric parietal cell morphology	1
abnormal small intestine crypts of Lieberkuhn morphology	1
abnormal large intestine crypts of Lieberkuhn morphology	1
diarrhea	1
increased CD4-positive, alpha-beta T cell number	1
abnormal small intestinal villus morphology	1
decreased tumor necrosis factor secretion	1
increased interleukin-1 beta secretion	1

+11 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Callithrix jacchus	B0KWC1	99.6%	Diamond
Plecturocebus moloch	B1MTG7	99.6%	Diamond
Papio anubis	A9X1A0	99.4%	Diamond
Bos taurus	O02810	99.3%	Diamond
Pongo abelii	Q5RAY1	98.6%	Diamond
Otolemur garnettii	B4UT09	98.2%	Diamond
Sus scrofa	Q5D891	97.9%	Diamond
Rhinolophus ferrumequinum	B2KI64	97.2%	Diamond
Sorex araneus	B3EX61	95.8%	Diamond
Xenopus tropicalis	A4IID4	94.7%	Diamond
Xenopus laevis	Q6GN16	94.7%	Diamond
Arabidopsis thaliana	Q9C680	88.5%	Diamond
Candida albicans SC5314	Q9UW20	57.5%	Diamond
Dictyostelium discoideum	P54677	54.3%	Diamond
Schizosaccharomyces pombe 972h-	Q9Y7K2	52.0%	Diamond
Saccharomyces cerevisiae S288C	P37297	45.1%	Diamond
Encephalitozoon cuniculi GB-M1	Q8SQY7	42.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SERPIND1	protein-coding	3053
CRKL	protein-coding	1399
SNAP29	protein-coding	9342
LINC01637	ncRNA	101928891
AIFM3	protein-coding	150209

Protein

Protein identifiers

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

Alternative names: Phosphatidylinositol 4-Kinase III alpha

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

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)

• 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 (170 total): helix 93, 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 by resolution:

PDB	Title	Method	Resolution (Å)
9B9G	Structure of the PI4KA complex bound to Calcineurin	ELECTRON MICROSCOPY	3.5
9OT6	Cryo-EM structure of the PI4KA complex bound to an EFR3 interfering nanobody (F3IN)	ELECTRON MICROSCOPY	3.54
6BQ1	Human PI4KIIIa lipid kinase complex	ELECTRON MICROSCOPY	3.6
9BAX	PI4KA complex bound to C-terminus of EFR3A	ELECTRON MICROSCOPY	3.65

Predicted structure (AlphaFold)

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

Antibody-complex structures (SAbDab)

1 antibodies co-crystallized with this protein: 9OT6

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted membrane proteins, Predicted intracellular proteins, Plasma proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; plasma membrane

Antibody reliability (HPA): IH approved · IF approved

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)

Type	Positions
Phosphoserine	260, 262, 265, 429, 1436, 230, 256, 257, 259
Phosphotyrosine	1154

Mutagenesis-validated functional residues (1)

Position	Phenotype
1957	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 6; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

6 pathways:

ID	Pathway	Evidence
R-HSA-1483248	Synthesis of PIPs at the ER membrane	curated
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane	curated
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-1483255	PI Metabolism	—
R-HSA-1483257	Phospholipid metabolism	—

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 (8): 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), myelination in peripheral nervous system (GO:0022011)

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

4 top-level categories:

Category	Pathways
PI Metabolism	2
Phospholipid metabolism	1
Metabolism of lipids	1
Metabolism	1

GO top-level categories

34 GO namespaces:

Category	Terms
cellular anatomical structure	3
glycerophospholipid biosynthetic process	2
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
intracellular signal transduction	1
symbiont-mediated perturbation of host membrane	1
primary metabolic process	1
Schwann cell development	1
peripheral nervous system axon ensheathment	1
myelination	1
phosphatidylinositol kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion 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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 22 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
host-mediated perturbation of viral process	BP	mutant phenotype
reorganization of cellular membranes to establish viral sites of replication	BP	mutant phenotype
cytoplasm	CC	direct assay
extracellular exosome	CC	high-throughput assay
focal adhesion	CC	high-throughput assay
membrane	CC	high-throughput assay
plasma membrane	CC	direct assay
cadherin binding	MF	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 1,336 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PI4KA	PI4K2B	Q8TCG2	780
PI4KA	PI4K2A	Q9BTU6	763
PI4KA	TTC7A	Q9ULT0	702
PI4KA	HYCC1	Q9BYI3	692
PI4KA	OSBP	P22059	685
PI4KA	EFR3B	Q9Y2G0	683
PI4KA	NCS1	P36610	658
PI4KA	EFR3A	Q14156	648
PI4KA	SNAP29	O95721	644
PI4KA	EIF2S1	P05198	633
PI4KA	THAP7	Q9BT49	626
PI4KA	LZTR1	Q8N653	605
PI4KA	TTC7B	Q86TV6	592
PI4KA	SERPIND1	P05546	584
PI4KA	PLEK2	Q9NYT0	574

IntAct

Human interaction partners of PI4KA in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
C8orf33	physical association	0.370	1
MRPL44	physical association	0.370	1
TNNT1	physical association	0.370	1
A2ML1	association	0.350	1
CIMIP5	association	0.350	1
EFR3A	association	0.350	1
GCLM	association	0.350	1
PI4KAP2	association	0.350	1
PPP3CB	association	0.350	1
PPP3CC	association	0.350	1
SNX21	association	0.350	1
STRN4	physical association	0.000	1

SIGNOR signaling

6 signaling 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”

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ P2X7 receptor signalling complex	12	ACTB, ACTN4, HSP90AB1, HSPA1A, PI4KA, PTPRB, SVIL, HSPA8, ITGB2, LAMA3, MPP3, P2RX7
Phosphatidylinositol 4-kinase complex	4	PI4KA, TTC7B, GSPT2, HYCC1

Disease & clinical

Cancer significance

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

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for PI4KA: 639 ClinVar records (55 pathogenic / likely pathogenic); 3 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	24
Likely pathogenic	31
Uncertain significance	234
Likely benign	147
Benign	121

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 55 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
1325874	NM_058004.4(PI4KA):c.6156_6159del (p.Thr2053fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1676320	NM_058004.4(PI4KA):c.1852C>T (p.Arg618Ter)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	7
1325872	NM_058004.4(PI4KA):c.3454G>A (p.Glu1152Lys)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
1675874	NM_058004.4(PI4KA):c.5974C>T (p.Pro1992Ser)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1325875	NM_058004.4(PI4KA):c.5456AAG[1] (p.Glu1820del)	Pathogenic	criteria provided, single submitter	2
1325877	NM_058004.4(PI4KA):c.5159C>T (p.Thr1720Ile)	Pathogenic	criteria provided, single submitter	2
1034208	NM_058004.4(PI4KA):c.3275C>A (p.Ser1092Ter)	Pathogenic	criteria provided, single submitter	1
1686063	NM_058004.4(PI4KA):c.2575-1G>A	Pathogenic	criteria provided, single submitter	1
2175799	NM_058004.4(PI4KA):c.2624del (p.Pro875fs)	Pathogenic	criteria provided, single submitter	1
2581427	NM_058004.4(PI4KA):c.2977del (p.Leu993fs)	Pathogenic	criteria provided, single submitter	1
2583000	NM_058004.4(PI4KA):c.1080del (p.Ser361fs)	Pathogenic	criteria provided, single submitter	1
4848356	NM_058004.4(PI4KA):c.591C>G (p.Tyr197Ter)	Pathogenic	criteria provided, single submitter	1
4880219	NM_058004.4(PI4KA):c.327del (p.Val110fs)	Pathogenic	criteria provided, single submitter	1
4891525	NM_058004.4(PI4KA):c.1696C>T (p.Arg566Ter)	Pathogenic	criteria provided, single submitter	1
4975084	NM_058004.4(PI4KA):c.1071+1G>A	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore PI4KA’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 31 predictions of 5,540):

Position(s)	Effect	Δscore	Sites
22:20709906–20709907	donor_loss	1.0000	4
22:20709998–20709999	acceptor_loss	1.0000	4
22:20712511	donor_gain	1.0000
22:20712612–20712613	acceptor_loss	1.0000	2
22:20712691	donor_loss	1.0000	2
22:20712865	acceptor_gain	1.0000
22:20713279–20713280	donor_loss	1.0000	5
22:20713391–20713392	acceptor_loss	1.0000	6
22:20713396	acceptor_gain	1.0000
22:20714456–20714457	donor_loss	1.0000	5

AlphaMissense

6,100 missense substitutions predicted likely pathogenic (of 13,866 scored), across 1,387 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M2041	9	0.983	1.000
M2000	9	0.974	0.999
M1964	9	0.931	0.999
M2004	9	0.926	0.999
M1666	9	0.886	0.991
M1691	9	0.867	0.997
D1854	8	1.000	1.000
D1957	8	1.000	1.000
D1853	8	0.999	1.000
D1858	8	0.999	1.000
H1959	8	0.999	1.000
N1962	8	0.999	1.000
D1975	8	0.999	1.000
D2091	8	0.999	1.000
H1973	8	0.998	0.999
F1978	8	0.998	1.000
F2049	8	0.998	1.000
D797	8	0.997	0.999
D987	8	0.997	0.999
H1685	8	0.997	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.25e-06
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000363

Disease associations

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

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis	Definitive	Autosomal recessive	3

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (16 panels, 14 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

16 panels:

Panel	Rating
Ataxia and cerebellar anomalies - childhood onset	green
Cerebellar hypoplasia	green
Cerebral malformation	green
DDG2P	green
Fetal anomalies	green
Hereditary ataxia and cerebellar anomalies, childhood onset	green
Hypotonic infant	green
Inherited white matter disorders	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Malformations of cortical development	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
White matter disorders and cerebral calcification - childhood onset	green
Hereditary spastic paraplegia, childhood onset	amber
Infantile enterocolitis & monogenic inflammatory bowel disease	amber

Mondo (6): polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis (MONDO:0014679), spastic paraplegia 84, autosomal recessive (MONDO:0030482), gastrointestinal defects and immunodeficiency syndrome 2 (MONDO:0030669), heparin cofactor 2 deficiency (MONDO:0012876), phenylketonuria (MONDO:0009861), PI4KA-related disorder (MONDO:1040012)

Orphanet (2): Autosomal recessive spastic paraplegia type 84 (Orphanet:631079), Phenylketonuria (Orphanet:716)

HPO phenotypes

showing 60 of 140 phenotypes (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
HP:0001347	Hyperreflexia
HP:0001349	Facial diplegia
HP:0001371	Flexion contracture
HP:0001511	Intrauterine growth retardation
HP:0001539	Omphalocele
HP:0001561	Polyhydramnios
HP:0001629	Ventricular septal defect
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus
HP:0001776	Bilateral talipes equinovarus
HP:0001888	Decreased total lymphocyte count
HP:0001890	Autoimmune hemolytic anemia
HP:0002015	Dysphagia
HP:0002020	Gastroesophageal reflux
HP:0002037	Inflammation of the large intestine
HP:0002061	Lower limb spasticity
HP:0002080	Intention tremor
HP:0002089	Pulmonary hypoplasia
HP:0002104	Apnea
HP:0002110	Bronchiectasis
HP:0002119	Ventriculomegaly
HP:0002126	Polymicrogyria
HP:0002194	Delayed gross motor development
HP:0002223	Absent eyebrow
HP:0002269	Abnormality of neuronal migration
HP:0002293	Alopecia of scalp
HP:0002307	Drooling
HP:0002359	Frequent falls
HP:0002385	Paraparesis
HP:0002392	EEG with polyspike wave complexes

GWAS associations

3 associations:

Study	Trait	p-value
GCST90002394_6	Monocyte percentage of white cells	2e-9
GCST009391_1282	Metabolite levels	2e-6
GCST007433_8	Fulminant type 1 diabetes	7e-6

EFO canonical traits (from GWAS)

2 canonical traits:

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

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
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
C562865	Heparin Cofactor II Deficiency *(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

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 224,426 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL477	ADENOSINE	4	224,426

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs165854	antipsychotics	Efficacy	Genotypes AG + GG is associated with decreased response to antipsychotics in people with Schizophrenia.	PMID:25209194

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)

133 measured of 306 human assays (308 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3121314	IC50	0.794 nM
CHEMBL3121318	IC50	2.5 nM
CHEMBL3121327	IC50	2.5 nM
CHEMBL3121334	IC50	4 nM
1-(4-(4-Propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo[h][1,6]naphthyridin-2(1H)-one	IC50	6.3 nM
CHEMBL3121323	IC50	6.3 nM
CHEMBL3121333	IC50	7.9 nM
CHEMBL3121321	IC50	16 nM
CHEMBL5091438	IC50	25 nM
2-[(1S)-1-cyclopropylethyl]-6-[4-methyl-2-[[6-(3-oxomorpholin-4-yl)-2-pyridinyl]amino]-1,3-thiazol-5-yl]-N-(oxetan-3-yl)-3-oxo-1H-isoindole-4-sulfonamide	IC50	32 nM	US-10961236: (S)-2-(1-cyclopropylethyl)-5-(4-methyl-2-((6-(2-oxopyrrolidin-1-yl)pyridin-2-yl)amino) thiazol-5-yl)-7-(methylsulfonyl)isoindolin-1-one as a phosphatidylinositol 3-kinase inhibitor
CHEMBL3121319	IC50	40 nM
CHEMBL3121322	IC50	50 nM
CHEMBL3121320	IC50	50 nM
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-3-(3-methyl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-[(E)-4-morpholin-4-ylbut-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-3-[3-(1,1-difluoroethyl)-1,2,4-oxadiazol-5-yl]prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-[(E)-3-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-1-[(E)-3-(3-tert-butyl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]-4-[7-(8-chloronaphthalen-1-yl)-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-1-[(E)-3-(3-tert-butyl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]-4-[7-(8-chloronaphthalen-1-yl)-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-4-morpholin-4-ylbut-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-3-(1-methylazetidin-2-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-[6-amino-4-methyl-3-(trifluoromethyl)-2-pyridinyl]-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-4-morpholin-4-ylbut-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[(6R,7R)-7-[6-amino-4-methyl-3-(trifluoromethyl)-2-pyridinyl]-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6-methyl-5,6,7,8-tetrahydroquinazolin-4-yl]-1-[(E)-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloro-7-fluoronaphthalen-1-yl)-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-[(E)-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloro-7-fluoronaphthalen-1-yl)-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-[(E)-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloro-7-fluoronaphthalen-1-yl)-2-[[(2R,8R)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]-1-[(E)-3-(3-propan-2-yl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-4-[(2R,6S)-2,6-dimethylmorpholin-4-yl]but-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(3-chloro-2-cyclopropylphenyl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-4-(6-oxa-3-azabicyclo[3.1.1]heptan-3-yl)but-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
2-[(2S)-4-[7-(3-chloro-2-cyclopropylphenyl)-8-fluoro-2-[[(2R,8S)-2-fluoro-1,2,3,5,6,7-hexahydropyrrolizin-8-yl]methoxy]pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-3-[(2R)-1-methylazetidin-2-yl]prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	55 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
CHEMBL3121329	IC50	63 nM
CHEMBL4558527	IC50	63 nM
CHEMBL1229535	IC50	64 nM
9-(6-aminopyridin-3-yl)-1-(3-(trifluoromethyl)phenyl)benzo[h][1,6]naphthyridin-2(1H)-one	EC50	118 nM
CHEMBL3121325	IC50	158 nM
CHEMBL1795875	IC50	170 nM
CHEMBL3600699	IC50	251 nM
2-[(2S)-4-[7-(8-chloronaphthalen-1-yl)-8-fluoro-2-(1,2,3,5,6,7-hexahydropyrrolizin-8-ylmethoxy)pyrido[4,3-d]pyrimidin-4-yl]-1-[(E)-3-(3-ethyl-1,2,4-oxadiazol-5-yl)prop-2-enoyl]piperazin-2-yl]acetonitrile	IC50	300 nM	US-20250129103: METHODS FOR TREATMENT OF CANCER
CHEMBL3121311	IC50	316 nM
CHEMBL3121313	IC50	316 nM
CHEMBL3121310	IC50	398 nM
CHEMBL4164334	IC50	405 nM
CHEMBL3901551	IC50	450 nM
CHEMBL3600698	IC50	501 nM
CHEMBL3121326	IC50	501 nM
CHEMBL3121317	IC50	501 nM
CHEMBL3947384	IC50	553 nM
CHEMBL3121328	IC50	631 nM
CHEMBL3986552	IC50	660 nM
CHEMBL4752128	IC50	681 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	affects cotreatment, decreases methylation, decreases expression	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	increases methylation, affects cotreatment, decreases methylation	1
Microplastics	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cycloheximide	decreases expression, increases reaction	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 244 trials:

NCT	Phase	Status	Title
NCT01082328	Phase 4	COMPLETED	Response to Kuvan® in Subjects With Phenylketonuria (PKU) in a 4 Weeks Testing Period
NCT01617070	Phase 4	COMPLETED	Effects of Kuvan on Melatonin Secretion
NCT01965912	Phase 4	COMPLETED	Kuvan®’s Effect on the Cognition of Children With Phenylketonuria
NCT02677870	Phase 4	COMPLETED	The Effectiveness of Kuvan in Amish PKU Patients
NCT03788343	Phase 4	COMPLETED	Phenylalanine and Its Impact on Cognition
NCT04227080	Phase 4	UNKNOWN	BH4 Responsiveness in PAH Deficiency PKU Patients
NCT06780332	Phase 4	ACTIVE_NOT_RECRUITING	Rapid Drug Desensitization Study in Adults Experiencing Hypersensitivity Reactions to Palynziq
NCT06901323	Phase 4	ACTIVE_NOT_RECRUITING	Effect of L-carnitine Supplementation on Phenylalanine and Brain-derived Neurotrophic Factor Levels in Infants and Children With Phenylketonuria
NCT07477691	Phase 4	RECRUITING	Immune Modulation During Palynziq® Treatment in Adults (IMPALA)
NCT02513940	Phase 4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	Phase 4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	Phase 4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	Phase 4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00104247	Phase 3	COMPLETED	Study to Evaluate the Safety and Efficacy of Phenoptin™ in Subjects With Phenylketonuria Who Have Elevated Phenylalanine Levels
NCT00225615	Phase 3	COMPLETED	A Phase 3, Multicenter, Open-Label Extension Study of Phenoptin in Subjects With PKU Who Have Elevated Phenylalanine Levels
NCT00272792	Phase 3	COMPLETED	Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet
NCT00332189	Phase 3	COMPLETED	Study of Phenoptin in Subjects With Phenylketonuria Who Participated in Protocols PKU-004 or PKU-006
NCT00838435	Phase 3	COMPLETED	Effect of Kuvan on Neurocognitive Function, Blood Phenylalanine Level, Safety, and Pharmacokinetics in Children With PKU
NCT01114737	Phase 3	COMPLETED	Safety and Therapeutic Effects of Sapropterin Dihydrochloride on Neuropsychiatric Symptoms in Phenylketonuria (PKU) Patients
NCT01376908	Phase 3	COMPLETED	Kuvan® in Phenylketonuria Patients Less Than 4 Years Old
NCT01732471	Phase 3	COMPLETED	Phase 3 Open-label Study to Evaluate the Response and Safety of Kuvan® in Subjects With Phenylketonuria
NCT01819727	Phase 3	COMPLETED	An Open-Label Phase 3 Study of BMN 165 for Adults With PKU Not Previously Treated w/ BMN 165
NCT01889862	Phase 3	COMPLETED	Phase 3 Study to Evaluate the Efficacy & Safety of Self-Administered Injections of BMN165 by Adults With PKU
NCT03694353	Phase 3	COMPLETED	Safety and Efficacy of Self Administered Injections of Pegvaliase (>40mg/Day Dose) in Adults With PKU
NCT05099640	Phase 3	COMPLETED	A Study of PTC923 in Participants With Phenylketonuria
NCT05166161	Phase 3	COMPLETED	A Long-Term Safety Study of PTC923 in Participants With Phenylketonuria
NCT05270837	Phase 3	ACTIVE_NOT_RECRUITING	Study to Evaluate the Safety and Efficacy of Pegvaliase in Adolescents (Ages 12-17) With Phenylketonuria
NCT05764239	Phase 3	TERMINATED	Efficacy and Safety of SYNB1934 in Patients With PKU (SYNPHENY-3)
NCT06302348	Phase 3	RECRUITING	A Study of Sepiapterin in Participants With Phenylketonuria (PKU)
NCT06628128	Phase 3	RECRUITING	A Long-Term Study of JNT-517 in Participants With Phenylketonuria
NCT06971731	Phase 3	RECRUITING	A Study of JNT-517 in Participants With Phenylketonuria (PKU)
NCT00104260	Phase 2	COMPLETED	Study to Evaluate the Response to and Safety of an 8-Day Course of Phenoptin™ Treatment in Subjects With Phenylketonuria
NCT00260000	Phase 2	COMPLETED	Study of BH4, a New and Simple Treatment of Mild PKU
NCT00841100	Phase 2	COMPLETED	Kuvan Therapy in Phenylketonuria (PKU): The Effect of Blood Phenylalanine Concentration on Kuvan Response
NCT00924703	Phase 2	COMPLETED	Long-Term Extension of Previous rAvPAL-PEG Protocols in Subjects With PKU (PAL-003)
NCT00925054	Phase 2	COMPLETED	Dose-Finding Study to Evaluate the Safety, Efficacy, & Tolerability of Multiple Doses of rAvPAL-PEG in Subjects With PKU
NCT01212744	Phase 2	COMPLETED	Safety, Tolerability, and Efficacy Study of rAvPAL-PEG Administered Daily in Subjects With Phenylketonuria (PKU)
NCT01395394	Phase 2	TERMINATED	Phenylketonuria, Oxidative Stress, and BH4
NCT01560286	Phase 2	COMPLETED	A Study to Evaluate Subcutaneously Administered rAvPAL-PEG in Patients With Phenylketonuria for 24 Weeks
NCT01977820	Phase 2	TERMINATED	Sapropterin on Cognitive Abilities in Young Adults With Phenylketonuria
NCT04534842	Phase 2	COMPLETED	Efficacy and Safety of SYNB1618 and SYNB1934 in Adult Patients With Phenylketonuria
NCT06637514	Phase 2	COMPLETED	A Phase 2 Study of JNT-517 in Adolescent Participants With Phenylketonuria
NCT06792240	Phase 2	COMPLETED	Iron Supplements Effect on b-Phe Levels in PKU Patients During 3 Years Study
NCT07694440	Phase 2	RECRUITING	A Study of MZE782 in Adults With PKU
NCT01648205	Phase 2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	Phase 2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	Phase 2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00244218	Phase 1	TERMINATED	Response to Phenylketonuria to Tetrahydrobiopterin (BH4)
NCT00634660	Phase 1	COMPLETED	Safety and Tolerability Study of rAvPAL-PEG to Treat Phenylketonuria
NCT00789568	Phase 1	COMPLETED	A Phase 1 Study to Evaluate Effects of Sapropterin Dihydrochloride on QTc Intervals in Healthy Adult Subjects
NCT04085666	Phase 1	COMPLETED	Pharmacodynamics, Safety, Tolerability and Pharmacokinetics of CDX-6114 in Patients With Phenylketonuria (PKU)
NCT04110496	Phase 1	TERMINATED	Safety and Tolerability of RTX-134 in Adults With Phenylketonuria
NCT04256655	Phase 1	WITHDRAWN	Safety, Tolerability, Pharmacodynamics and Pharmacokinetics of CDX 6114 in PKU Patients
NCT05222178	Phase 1	TERMINATED	Safety and Efficacy of HMI-103 in Participants With Classical PKU Due to PAH Deficiency
NCT07241234	Phase 1	RECRUITING	A Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-181 in Subjects With Phenylketonuria
NCT07255599	Phase 1	ACTIVE_NOT_RECRUITING	Evaluation of BH4 Responsiveness in Our PKU Patients
NCT07672756	Phase 1	RECRUITING	A Clinical Study on the Safety and Tolerability of PL54 Injection in Adult Patients With Phenylketonuria (PKU)
NCT07685210	Phase 1	RECRUITING	GenSci144 Tablets Phase I Clinical Trial
NCT07713758	Phase 1	RECRUITING	A Trial to Examine if Repinatrabit is Processed Differently in Adults With Reduced Liver or Kidney Function Compared to Adults With Normal Liver and Kidney Function
NCT00316459	Phase 1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PI4KA across ~30M SureChEMBL compounds — explore on Sugi Predict.