PI4KB

Summary

PI4KB (phosphatidylinositol 4-kinase beta, HGNC:8984) is a protein-coding gene on chromosome 1q21.3, encoding Phosphatidylinositol 4-kinase beta (Q9UBF8). Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). It is a selective cancer dependency (DepMap: 23.3% of cell lines).

Enables 1-phosphatidylinositol 4-kinase activity and 14-3-3 protein binding activity. Involved in inner ear development and phosphatidylinositol phosphate biosynthetic process. Acts upstream of or within lysosome organization. Located in Golgi membrane. Is active in cytoplasmic side of trans-Golgi network membrane. Implicated in autosomal dominant nonsyndromic deafness 87.

Source: NCBI Gene 5298 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• Gene–disease (curated): hearing loss, autosomal dominant 87 (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 102 total — 4 pathogenic
• Regional missense constraint (gnomAD): 2 of 5 regions constrained (≈10% of expected missense variation)
• GTEx eGene: eQTL in 6 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 5
• ChEMBL bioactivity: 20 clinical-phase molecules tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 23.3% of screened cell lines
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.42 (moderately constrained)
• MANE Select transcript: NM_001369623
• Notable: 102 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8984
Approved symbol	PI4KB
Name	phosphatidylinositol 4-kinase beta
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	PI4K-BETA, pi4K92
Ensembl gene	ENSG00000143393
Ensembl biotype	protein_coding
OMIM	602758
Entrez	5298

Gene structure

Transcript identifiers

Ensembl transcripts: 53 — 48 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000368873

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

ENST00000368873, ENST00000368872, ENST00000368874, ENST00000368875, ENST00000430800, ENST00000438243, ENST00000446339, ENST00000455060, ENST00000460323, ENST00000469239, ENST00000489223, ENST00000489889, ENST00000529142, ENST00000852743, ENST00000852744, ENST00000852745, ENST00000852746, ENST00000852747, ENST00000852748, ENST00000852749, ENST00000852750, ENST00000852751, ENST00000852752, ENST00000852753, ENST00000852754, ENST00000852755, ENST00000852756, ENST00000852757, ENST00000852758, ENST00000852759, ENST00000852760, ENST00000852761, ENST00000852762, ENST00000852763, ENST00000852764, ENST00000852765, ENST00000933551, ENST00000933552, ENST00000933553, ENST00000933554, ENST00000933555, ENST00000933556, ENST00000933557, ENST00000933558, ENST00000933559, ENST00000943240, ENST00000943241, ENST00000943242, ENST00000943243, ENST00000982011, ENST00001050726, ENST00001050727, ENST00001145723

RefSeq mRNA: 11 — MANE Select: NM_001369623 NM_001198773, NM_001198774, NM_001198775, NM_001330721, NM_001369623, NM_001369624, NM_001369625, NM_001369626, NM_001369628, NM_001369629, NM_002651

CCDS: CCDS55637, CCDS55638, CCDS81376, CCDS993

Canonical transcript exons

ENST00000368873 — 12 exons

Exon	Start	End
ENSE00000959789	151294409	151294541
ENSE00000959790	151294018	151294138
ENSE00001448172	151291804	151293033
ENSE00001668188	151302194	151302298
ENSE00001687893	151306136	151306363
ENSE00001690709	151327271	151327416
ENSE00001696456	151298808	151299073
ENSE00001705050	151301844	151301967
ENSE00001756379	151310211	151310255
ENSE00001791799	151303541	151303650
ENSE00003463601	151315573	151316509
ENSE00003521777	151307574	151307801

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 97.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.2016 / max 124.1563, expressed in 1815 samples.

Highest expression (Bgee): lobe of thyroid gland, tibial nerve, uterine tube, body of uterus, thyroid gland.

Genetic regulation across tissues (GTEx eQTL / sQTL)

PI4KB is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

9 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Nerve Tibial	sqtl	9.4e-04	-0.30	1:151216941:C:T
Skin Sun Exposed Lower leg	eqtl	3.0e-03	+0.46	1:151247798:G:T
Adipose Subcutaneous	eqtl	3.6e-03	+0.45	1:151345018:C:T
Whole Blood	eqtl	3.8e-03	-0.16	1:151195125:C:T
Testis	sqtl	5.3e-03	+0.36	1:151365312:A:G
Brain Cortex	eqtl	1.1e-02	+1.25	1:151738548:T:A
Esophagus Muscularis	sqtl	1.4e-02	+0.35	1:151267532:A:G
Thyroid	eqtl	2.0e-02	-0.11	1:151476662:G:A
Cells EBV-transformed lymphocytes	eqtl	2.3e-02	+0.68	1:151327376:T:TTCCC

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
14424	19.2131	1806
14427	10.1016	1786
14428	3.5831	1498
14426	0.2419	71
14425	0.0619	34

Top tissues by expression

showing 100 of 294 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	97.57	gold quality
tibial nerve	UBERON:0001323	97.50	gold quality
left lobe of thyroid gland	UBERON:0001120	97.46	gold quality
right uterine tube	UBERON:0001302	97.46	gold quality
body of uterus	UBERON:0009853	97.13	gold quality
thyroid gland	UBERON:0002046	97.06	gold quality
secondary oocyte	CL:0000655	97.03	gold quality
endocervix	UBERON:0000458	97.01	gold quality
right ovary	UBERON:0002118	96.71	gold quality
left ovary	UBERON:0002119	96.69	gold quality
ectocervix	UBERON:0012249	96.68	gold quality
adenohypophysis	UBERON:0002196	96.63	gold quality
left uterine tube	UBERON:0001303	96.57	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.57	gold quality
stromal cell of endometrium	CL:0002255	96.54	gold quality
pituitary gland	UBERON:0000007	96.37	gold quality
cerebellar hemisphere	UBERON:0002245	96.34	gold quality
cerebellar cortex	UBERON:0002129	96.27	gold quality
skin of leg	UBERON:0001511	96.23	gold quality
skin of abdomen	UBERON:0001416	96.09	gold quality
mucosa of stomach	UBERON:0001199	96.08	gold quality
lower esophagus mucosa	UBERON:0035834	96.07	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.99	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.97	gold quality
spleen	UBERON:0002106	95.94	gold quality
body of stomach	UBERON:0001161	95.88	gold quality
metanephros cortex	UBERON:0010533	95.83	gold quality
minor salivary gland	UBERON:0001830	95.79	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.77	gold quality
right coronary artery	UBERON:0001625	95.75	gold quality
cerebellum	UBERON:0002037	95.65	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.55	gold quality
lower esophagus	UBERON:0013473	95.54	gold quality
upper lobe of left lung	UBERON:0008952	95.52	gold quality
descending thoracic aorta	UBERON:0002345	95.48	gold quality
right lung	UBERON:0002167	95.44	gold quality
granulocyte	CL:0000094	95.42	gold quality
ascending aorta	UBERON:0001496	95.39	gold quality
thoracic aorta	UBERON:0001515	95.35	gold quality
transverse colon	UBERON:0001157	95.29	gold quality
saliva-secreting gland	UBERON:0001044	95.28	gold quality
fundus of stomach	UBERON:0001160	95.27	gold quality
aorta	UBERON:0000947	95.17	gold quality
vagina	UBERON:0000996	95.17	gold quality
upper lobe of lung	UBERON:0008948	95.14	gold quality
coronary artery	UBERON:0001621	95.10	gold quality
omental fat pad	UBERON:0010414	95.10	gold quality
peritoneum	UBERON:0002358	95.09	gold quality
popliteal artery	UBERON:0002250	95.08	gold quality
tibial artery	UBERON:0007610	95.08	gold quality
left coronary artery	UBERON:0001626	95.07	gold quality
right frontal lobe	UBERON:0002810	95.07	gold quality
mouth mucosa	UBERON:0003729	95.05	gold quality
esophagus	UBERON:0001043	95.03	gold quality
zone of skin	UBERON:0000014	95.02	gold quality
esophagus mucosa	UBERON:0002469	94.82	gold quality
left testis	UBERON:0004533	94.81	gold quality
smooth muscle tissue	UBERON:0001135	94.80	gold quality
stomach	UBERON:0000945	94.79	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.79	gold quality
ovary	UBERON:0000992	94.77	gold quality
small intestine	UBERON:0002108	94.77	gold quality
left adrenal gland	UBERON:0001234	94.74	gold quality
gastrocnemius	UBERON:0001388	94.74	gold quality
gall bladder	UBERON:0002110	94.73	gold quality
right testis	UBERON:0004534	94.71	gold quality
left adrenal gland cortex	UBERON:0035825	94.71	gold quality
right adrenal gland cortex	UBERON:0035827	94.69	gold quality
sural nerve	UBERON:0015488	94.59	gold quality
mucosa of transverse colon	UBERON:0004991	94.57	gold quality
apex of heart	UBERON:0002098	94.55	gold quality
right adrenal gland	UBERON:0001233	94.54	gold quality
adrenal cortex	UBERON:0001235	94.50	gold quality
myometrium	UBERON:0001296	94.50	gold quality
body of pancreas	UBERON:0001150	94.49	gold quality
subcutaneous adipose tissue	UBERON:0002190	94.28	gold quality
right atrium auricular region	UBERON:0006631	94.28	gold quality
muscle of leg	UBERON:0001383	94.23	gold quality
adrenal gland	UBERON:0002369	94.18	gold quality
mammary duct	UBERON:0001765	94.17	gold quality
rectum	UBERON:0001052	94.08	gold quality
oocyte	CL:0000023	94.07	gold quality
sigmoid colon	UBERON:0001159	93.99	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.96	gold quality
islet of Langerhans	UBERON:0000006	93.90	gold quality
pancreas	UBERON:0001264	93.83	gold quality
colon	UBERON:0001155	93.78	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	93.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	93.74	gold quality
right lobe of liver	UBERON:0001114	93.71	gold quality
intestine	UBERON:0000160	93.66	gold quality
cortical plate	UBERON:0005343	93.66	gold quality
amygdala	UBERON:0001876	93.63	gold quality
cardiac atrium	UBERON:0002081	93.60	gold quality
anatomical system	UBERON:0000467	93.59	gold quality
paraflocculus	UBERON:0005351	93.55	gold quality
large intestine	UBERON:0000059	93.54	gold quality
uterine cervix	UBERON:0000002	93.53	gold quality
hypothalamus	UBERON:0001898	93.51	gold quality
lymph node	UBERON:0000029	93.48	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 78 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	73.5	low
Locus coeruleus	tissue	67.4
Hippocampus	tissue	66.0	medium
Nucleus accumbens	tissue	63.9
Choroid plexus	tissue	62.7
Postcentral gyrus	tissue	62.2
Skin 1	tissue	57.2	low
Smooth muscle	tissue	57.0	not detected
Pituitary gland	tissue	55.1
Tongue	tissue	54.9
Endometrium 1	tissue	53.7	not detected
Epididymis	tissue	52.0	medium
Parathyroid gland	tissue	51.6	not detected
Vagina	tissue	49.4	not detected
Spleen	tissue	48.8	not detected
Ovary	tissue	48.0	not detected
Thyroid gland	tissue	47.7	low
Fallopian tube	tissue	46.6	medium
Tonsil	tissue	44.1	medium
Skeletal muscle	tissue	43.5	low
Lymph node	tissue	43.4	low
Retina	tissue	43.4
Thymus	tissue	42.2
Salivary gland	tissue	41.2	not detected
Rectum	tissue	41.0	low
Lung	tissue	40.8	medium
Seminal vesicle	tissue	39.4
Prostate	tissue	39.0	not detected
Small intestine	tissue	37.6	low
Gallbladder	tissue	37.5	medium
Placenta	tissue	36.7	medium
Esophagus	tissue	36.4	not detected
Adipose tissue	tissue	35.9	medium
Stomach 1	tissue	35.7	medium
Testis	tissue	35.6	medium
Cervix	tissue	35.3	not detected
Urinary bladder	tissue	35.3	not detected
Breast	tissue	35.1	medium
Pancreas	tissue	33.9	medium
Colon	tissue	33.1	low
Duodenum	tissue	33.0	medium
Adrenal gland	tissue	31.0	medium
Appendix	tissue	30.9	low
Heart muscle	tissue	29.9	medium
Kidney	tissue	29.8	low
Pons	tissue	28.3
Thalamus	tissue	28.2
Hypothalamus	tissue	28.1
Cerebellum	tissue	27.7	medium
Cerebral cortex	tissue	27.5	medium
Somatosensory cortex	tissue	27.5
Substantia nigra	tissue	27.4
Olfactory bulb	tissue	27.3
Hippocampal formation	tissue	27.2
Midbrain	tissue	27.0
Superior colliculi	tissue	27.0
Basal ganglia	tissue	26.8	medium
Occipital cortex	tissue	26.0
Putamen	tissue	25.9
Liver	tissue	25.9	medium

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Parieto-temporal junction (white matter) (89.1), Temporal white matter (87.6), Flocculonodular lobe (84.8), Corpus callosum, genu (white matter) (84.0), Corpus callosum, splenium (white matter) (83.2).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting PI4KB by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 72 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-623	99.76	68.16	1170
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-6883-5P	99.69	68.05	3785

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.421, missense Z 4.68 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000368873 splits into 5 regions with different missense tolerance; 2 are missense-constrained (≈10% 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
1:151,292,855–151,292,904	2 / 22.9	0.09	yes (p 1.3e-05)
1:151,292,905–151,294,131	70 / 108.1	0.65	no
1:151,294,132–151,298,859	19 / 77.8	0.24	yes (p 2.6e-11)
1:151,298,860–151,307,800	246 / 430.1	0.57	no
1:151,307,801–151,316,481	314 / 397.8	0.79	no
DepMap (CRISPR cell-line fitness): dependent in 23.3% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): KCL-22 (-1.635), AML-193 (-1.411), NCI-H1869 (-1.393), NB-4 (-1.363), DK-MG (-1.237), EW-22 (-1.214), OUMS-23 (-1.201), UW228 (-1.146), KMRC-2 (-1.14), COG-E-352 (-1.131), UM-UC-5 (-1.122), OCI-LY18 (-1.106), NCC-UPS1-C1 (-1.101), JIMT-1 (-1.099), UM-HACC-2A (-1.089).

Literature-anchored findings (GeneRIF, showing 40)

• Characterization of type II phosphatidylinositol 4-kinase isoforms reveals association of the enzymes with endosomal vesicular compartments (PMID:11923287)
• determination that the enzyme is primarily cytosolic, and it associates peripherally with plasma membranes, endoplasmic reticulum, and the Golgi (PMID:12324459)
• PI4KIIIbeta (PIK4CB) and PI4KIIalpha (PIK4CA) localize to discrete subcompartments of the Golgi complex in Madin-Darby canine kidney (MDCK) cells. (PMID:15634669)
• PI 4-kinase beta is a key enzyme in the control of spingomyelin synthesis by controlling the flow of ceramide from the ER to the Golgi compartment (PMID:17003043)
• there is a physical and functional relationship between eEF1A2 and PI4KIIIbeta (PMID:17088255)
• PI4KIIalpha or PI4KIIbeta knockdown, but not type III PI4Kbeta knockdown, inhibits Listeria internalization. (PMID:17555516)
• Work suggests an important role for both eEF1A2 and PI4KIIIbeta in the control of PI(4,5)P(2) signaling and actin remodeling. (PMID:18474610)
• 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)
• Knockdown of PI4KIIalpha does not inhibit EGF-stimulated Akt phosphorylation. (PMID:21218173)
• Study identify the molecular chaperone Hsp90 as a binding partner of PI4KIIbeta, but not of PI4KIIalpha. (PMID:21330372)
• Our data establish PtdIns(4,5)P(2) as a direct activator of TRPV6 and demonstrate that intracellular ATP regulates the channel indirectly as a substrate for type III PI4Ks (PMID:21810903)
• The PI4KIIIbeta likely plays an important role in mammary neoplasia and acinar development. (PMID:21851817)
• results indicate that a viral protein/ACBD3/PI4KB complex is formed to synthesize PI4P at the AiV RNA replication sites and plays an essential role in viral RNA replication (PMID:22124328)
• Phosphatidylinositol 4-kinase IIIbeta is required for severe acute respiratory syndrome coronavirus spike-mediated cell entry. (PMID:22253445)
• The 3A protein of picornaviruses utilizes the golgi adaptor protein ACBD3 to recruit PI4KIIIbeta. (PMID:22258260)
• During authentic HCV infection, PI4P plays an integral role in virus replication; the vesicular transport proteins ARF1 and GBF1 colocalized with PI4KIIIbeta and were both required for HCV replication. (PMID:22359663)
• The lipid kinase PI4KIIIbeta preserves lysosomal identity. (PMID:23258225)
• These results suggest that poliovirus proteins modulate PI4KB activity and provide PI4P for recruitment of OSBP to accumulate unesterified cholesterol on virus-induced membrane structure for formation of a virus replication complex. (PMID:24527995)
• Host ACBD3, PI4KIIIBETA and Aichi virus proteins complexes enhances phosphatidylinositol 4-phosphate synthesis and is critical for viral replication. (PMID:24672044)
• Authors found that NS5A and PI4KB competed for association of acyl-coenzyme A binding domain containing protein 3 (ACBD3), which inhibited hepatitis C virus replication. (PMID:24792752)
• these data provide a mechanism for how PI4KIIIbeta coordinates Rab11 and its effectors on PI4P-enriched membranes and also provide strategies for the design of specific inhibitors that could potentially target plasmodial PI4KIIIbeta to combat malaria. (PMID:24876499)
• PI4KIIIbeta likely plays a role in breast oncogenesis and that cooperation between Rab11a and PI4KIIIbeta represents a novel Akt activation pathway. (PMID:24962317)
• Although human rhinovirus 3A protein was previously shown to interact with ACBD3, these data suggest that PI4KIIIbeta recruitment occurred independently of both GBF1 and ACBD3. (PMID:25410869)
• Analysis reveals novel aspects of the PI4KIIIb-Rab11 complex and determines binding and catalytic sites of the kinase. (PMID:26756197)
• Data show that ACBD3 can recruit PI4KB to model membranes as well as redirect PI4KB to cellular membranes where it is not naturally found. Also, results show that ACBD3 regulates the enzymatic activity of PI4KB kinase through membrane recruitment rather than allostery. (PMID:27009356)
• 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)
• esults show that Aichi virus 3A protein activates the lipid kinase activity of PI4KIIIb,which activation is sensitized by the protein ACBD3. The interfaces between PI4KIIIbeta-ACBD3 and ACBD3-3A were mapped with hydrogen-deuterium exchange mass spectrometry. (PMID:27989622)
• PI4KIIIbeta interaction with the VHS domain of GGA2 affected PI4KIIIbeta localization. (PMID:28289207)
• several disordered regions of PI4KB become protected from proteolytical degradation upon 14-3-3 binding. (PMID:28864297)
• These results suggest that PtdIns 4-kinase II beta may be a novel regulator of Par-4 through protein-protein interactions. (PMID:30606737)
• In vitro reconstitution revealed that the membrane is necessary for the formation of ACBD3:PI4KB:Rab11 protein complex at physiological (nanomolar) concentrations. (PMID:30679637)
• Altogether, these data provide new insight into the central role of ACBD3 in recruiting PI4KB by enterovirus 3A and reveal the minimal domains of ACBD3 involved in recruiting PI4KB and supporting enterovirus replication. (PMID:30755512)
• Two variant prioritization pipelines based on AR inheritance and runs of homozygosity (ROH), identified two novel homozygous variants in KCNJ10 and PI4KB and five rare homozygous variants in PVRL4, RORC, FLG2, FCRL1, NIT1 and one common homozygous variant in HSPA6 segregating in all four patients (PMID:31640787)
• PI4KB on Inclusion Bodies Formed by ER Membrane Remodeling Facilitates Replication of Human Parainfluenza Virus Type 3. (PMID:31747597)
• Phosphatidylinositol 4-kinase III beta regulates cell shape, migration, and focal adhesion number. (PMID:32583740)
• Phosphatidylinositol 4-kinase IIIbeta mediates contraction-induced GLUT4 translocation and shows its anti-diabetic action in cardiomyocytes. (PMID:33090289)
• Phosphatidylinositol 4-kinase beta mutations cause nonsyndromic sensorineural deafness and inner ear malformation. (PMID:33358777)
• circSLC6A6 Sponges miR-497-5p to Promote Endometrial Cancer Progression via the PI4KB/Hedgehog Axis. (PMID:34258297)
• The C10orf76-PI4KB axis orchestrates CERT-mediated ceramide trafficking to the distal Golgi. (PMID:37195633)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pi4kb	ENSDARG00000040111
mus_musculus	Pi4kb	ENSMUSG00000038861
rattus_norvegicus	Pi4kb	ENSRNOG00000021024
drosophila_melanogaster	fwd	FBGN0004373
caenorhabditis_elegans		WBGENE00018076

Paralogs (9): PIK3C2A (ENSG00000011405), PIK3CB (ENSG00000051382), PIK3C3 (ENSG00000078142), PIK3CG (ENSG00000105851), PIK3CA (ENSG00000121879), PIK3C2B (ENSG00000133056), PIK3C2G (ENSG00000139144), PIK3CD (ENSG00000171608), PI4KA (ENSG00000241973)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1334433) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 9 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal Schwann cell morphology	1
impaired coordination	1
abnormal gait	1
limb grasping	1
abnormal sciatic nerve morphology	1
decreased nerve conduction velocity	1
abnormal node of Ranvier morphology	1
spasticity	1
decreased myelin sheath amount	1

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
Otolemur garnettii	B4UT09	98.2%	Diamond
Rhinolophus ferrumequinum	B2KI64	97.2%	Diamond
Cryptococcus deneoformans JEC21	P0CP60	96.7%	Diamond
Cryptococcus deneoformans B-3501A	P0CP61	96.7%	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-	Q9USR3	46.0%	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
RFX5-AS1	ncRNA	101927886
PSMD4	protein-coding	5710
ZNF687	protein-coding	57592
RFX5	protein-coding	5993
PIP5K1A	protein-coding	8394
ZNF687-AS1	ncRNA	100507670
PSMB4	protein-coding	5692
SELENBP1	protein-coding	8991
VPS72	protein-coding	6944
POGZ	protein-coding	23126

Protein

Protein identifiers

Phosphatidylinositol 4-kinase beta — Q9UBF8 (reviewed: Q9UBF8)

Alternative names: NPIK, PI4K92, PI4KIII

All UniProt accessions (8): A0A0A0MSL0, A0A0B4J1S8, A6PVV8, Q9UBF8, E9PL47, F8W860, H0Y4F8, H0YCW3

UniProt curated annotations — full annotation on UniProt →

Function. Phosphorylates phosphatidylinositol (PI) in the first committed step in the production of the second messenger inositol-1,4,5,-trisphosphate (PIP). May regulate Golgi disintegration/reorganization during mitosis, possibly via its phosphorylation. Involved in Golgi-to-plasma membrane trafficking. May play an important role in the inner ear development. (Microbial infection) Plays an essential role in Aichi virus RNA replication. Recruited by ACBD3 at the viral replication sites. (Microbial infection) Required for cellular spike-mediated entry of human coronavirus SARS-CoV.

Subunit / interactions. Interacts with ARF1 and ARF3 in the Golgi complex, but not with ARF4, ARF5 or ARF6. Interacts with NCS1/FREQ in a calcium-independent manner. Interacts with CALN1/CABP8 and CALN2/CABP7; in a calcium-dependent manner; this interaction competes with NCS1/FREQ binding. Interacts with ACBD3. Interacts with ARMH3, YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ and SFN. Interacts with GGA2 (via VHS domain); the interaction is important for PI4KB location at the Golgi apparatus membrane. Interacts with ATG9A. (Microbial infection) Interacts with Aichi virus protein 3A. Part of a complex Aichi virus protein 3A/ACBD3/PI4KB that allows the synthesis of PI4P at the viral RNA replication sites.

Subcellular location. Endomembrane system. Mitochondrion outer membrane. Rough endoplasmic reticulum membrane. Golgi apparatus. Golgi apparatus membrane. Cytoplasm. Perinuclear region.

Tissue specificity. Widely expressed with highest levels in heart, skeletal muscle, pancreas, testis and ovary. Weakly expressed in liver. Expressed in the innear ear in the epithelium of the spinal organ of corti.

Disease relevance. Deafness, autosomal dominant, 87 (DFNA87) [MIM:620281] A form of non-syndromic, sensorineural hearing loss. Sensorineural hearing loss results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. DFNA87 is characterized by prelingual, profound sensorineural hearing loss with inner ear anomalies, including cochlear maldevelopment, absence of the osseous spiral lamina, and/or an enlarged vestibular aqueduct. The disease may be caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by wortmannin and adenosine. Increased kinase activity upon interaction with NCS1/FREQ. (Microbial infection) Activated by Aichi virus protein 3A, this activation is sensitized by ACBD3.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q9UBF8-1	1, NPIK-B	yes
Q9UBF8-2	2, NPIK-C
Q9UBF8-3	3

RefSeq proteins (11): NP_001185702, NP_001185703, NP_001185704, NP_001317650, NP_001356552, NP_001356553, NP_001356554, NP_001356555, NP_001356557, NP_001356558, NP_002642 (=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
IPR018936	PI3/4_kinase_CS	Conserved_site
IPR036940	PI3/4_kinase_cat_sf	Homologous_superfamily
IPR049160	PI4KB-PIK1_PIK	Domain
IPR057754	PI4-kinase_beta/PIK1_cat	Domain

Pfam: PF00454, PF21245

Enzyme classification (BRENDA)

• EC 2.7.1.67 — 1-phosphatidylinositol 4-kinase (BRENDA: 26 organisms, 60 substrates, 371 inhibitors, 71 Km, 4 kcat entries)

Substrate kinetics (BRENDA)

4 substrates with measured Km, best-characterized 4. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.018–1.7	43
PHOSPHATIDYLINOSITOL	0.017–1	18
1-PHOSPHATIDYL-1D-MYO-INOSITOL	0.016–0.1	2
GTP	0.62	1

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 (106 total): helix 32, strand 17, modified residue 14, mutagenesis site 14, region of interest 7, sequence conflict 7, sequence variant 4, turn 3, compositionally biased region 2, domain 2, splice variant 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

20 structures by resolution:

PDB	Title	Method	Resolution (Å)
8Q6F	HUMAN PI4KIIIB IN COMPLEX WITH COVALENTLY BOUND INHIBITOR (COMPOUND 4)	X-RAY DIFFRACTION	1.51
8Q6G	HUMAN PI4KIIIB IN COMPLEX WITH COVALENTLY BOUND INHIBITOR (COMPOUND 8)	X-RAY DIFFRACTION	1.54
8Q6H	HUMAN PI4KIIIB IN COMPLEX WITH COVALENTLY BOUND INHIBITOR (COMPOUND 11)	X-RAY DIFFRACTION	1.94
5NAS	Crystal structure of human 14-3-3 zeta in complex with PI4KIIIB peptide	X-RAY DIFFRACTION	2.08
5LX2	Lt 14-3-3 in complex with PI4KIIIB peptide	X-RAY DIFFRACTION	2.58
5C46	Crystal structure of an engineered construct of phosphatidylinositol 4 kinase III beta in …	X-RAY DIFFRACTION	2.65
6GL3	Crystal structure of human Phosphatidylinositol 4-kinase III beta (PI4KIIIbeta) in …	X-RAY DIFFRACTION	2.77
4D0L	Phosphatidylinositol 4-kinase III beta-PIK93 in a complex with Rab11a- GTP gammaS	X-RAY DIFFRACTION	2.94
8VOF	GI targeted CpPI4K inhibitor	X-RAY DIFFRACTION	3
5C4G	Crystal structure of an engineered construct of phosphatidylinositol 4 kinase III beta …	X-RAY DIFFRACTION	3.2
5EUQ	Crystal structure of an engineered construct of phosphatidylinositol 4 kinase III beta …	X-RAY DIFFRACTION	3.2
5FBR	PI4KB in complex with Rab11 and the MI359 Inhibitor	X-RAY DIFFRACTION	3.28
5FBV	PI4KB in complex with Rab11 and the MI364 Inhibitor	X-RAY DIFFRACTION	3.29
4WAE	Phosphatidylinositol 4-kinase III beta crystallized with ATP	X-RAY DIFFRACTION	3.32
5FBL	PI4KB in complex with Rab11 and the MI356 Inhibitor	X-RAY DIFFRACTION	3.37
4WAG	Phosphatidylinositol 4-kinase III beta crystallized with MI103 inhibitor	X-RAY DIFFRACTION	3.41
5FBW	PI4KB in complex with Rab11 and the MI369 Inhibitor	X-RAY DIFFRACTION	3.49
5FBQ	PI4KB in complex with Rab11 and the MI358 Inhibitor	X-RAY DIFFRACTION	3.79
4D0M	Phosphatidylinositol 4-kinase III beta in a complex with Rab11a-GTP- gamma-S and the …	X-RAY DIFFRACTION	6
2N73	Solution structure of the ACBD3:PI4KB complex	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UBF8-F1	72.97	0.48

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Metabolic proteins, Predicted intracellular proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): golgi apparatus

Antibody reliability (HPA): IH approved · IF supported

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 (14)

Type	Positions
Phosphoserine	294, 258, 266, 275, 277, 284, 294, 428, 511
N-acetylglycine	2
Phosphothreonine	263, 438, 517, 519

Mutagenesis-validated functional residues (14)

Position	Phenotype
40–42	small decrease in armh3-binding. no effect on acbd3-, nor rab11b-binding.
42	no loss of interaction with acbd3.
43–45	drastically decreased acbd3-binding. no effect on armh3-, nor rab11b-binding.
43	loss of interaction with acbd3.
44	loss of interaction with acbd3.
46–47	no effect on acbd3-, armh3-, nor rab11b-binding.
47	no loss of interaction with acbd3.
49–50	no effect on acbd3-, armh3-, nor rab11b-binding.
52	no effect on acbd3-, armh3-, nor rab11b-binding.
53–54	drastically decreased armh3- and rab11b-binding. 6-fold increase in acbd3-binding.
55–56	drastically decreased acbd3-binding. no effect on armh3-, nor rab11b-binding.
55	loss of interaction with acbd3.
56	loss of interaction with acbd3.
57–59	no effect on acbd3-, armh3-, nor rab11b-binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
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: 200 (showing top): MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, GU_PDEF_TARGETS_DN, GOBP_VACUOLE_ORGANIZATION, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, TGCACTT_MIR519C_MIR519B_MIR519A, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, CAGCTG_AP4_Q5, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, SP1_Q2_01, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS

GO Biological Process (8): phosphatidylinositol biosynthetic process (GO:0006661), receptor-mediated endocytosis (GO:0006898), lysosome organization (GO:0007040), signal transduction (GO:0007165), phosphatidylinositol phosphate biosynthetic process (GO:0046854), phosphatidylinositol-mediated signaling (GO:0048015), inner ear development (GO:0048839), lipid metabolic process (GO:0006629)

GO Molecular Function (7): 1-phosphatidylinositol 4-kinase activity (GO:0004430), ATP binding (GO:0005524), 14-3-3 protein binding (GO:0071889), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): Golgi membrane (GO:0000139), cytoplasm (GO:0005737), mitochondrial outer membrane (GO:0005741), endosome (GO:0005768), Golgi apparatus (GO:0005794), cytosol (GO:0005829), membrane (GO:0016020), rough endoplasmic reticulum membrane (GO:0030867), perinuclear region of cytoplasm (GO:0048471), cytoplasmic side of trans-Golgi network membrane (GO:0160281), endomembrane system (GO:0012505)

Reactome top-level categories

4 top-level categories:

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

GO top-level categories

40 GO namespaces:

Category	Terms
cellular anatomical structure	5
cytoplasm	3
glycerophospholipid biosynthetic process	2
bounding membrane of organelle	2
endomembrane system	2
phosphatidylinositol metabolic process	1
endocytosis	1
vesicle-mediated transport	1
lytic vacuole organization	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signal transduction	1
ear development	1
animal gross anatomical part developmental process	1
primary metabolic process	1
phosphatidylinositol kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
protein binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
Golgi apparatus	1
intracellular anatomical structure	1
mitochondrial membrane	1
organelle outer membrane	1
cytoplasmic vesicle	1
intracellular membrane-bounded organelle	1
endoplasmic reticulum membrane	1
rough endoplasmic reticulum	1
trans-Golgi network membrane	1
cytoplasmic side of membrane	1
vacuole	1
plasma membrane	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 8 of 26 annotations. The rest are phylogenetic / computational / electronic (IEA).

8 experimentally-supported GO terms:

GO term	NS	Evidence
inner ear development	BP	mutant phenotype
lysosome organization	BP	direct assay
phosphatidylinositol phosphate biosynthetic process	BP	direct assay
Golgi apparatus	CC	direct assay
Golgi membrane	CC	direct assay
cytoplasmic side of trans-Golgi network membrane	CC	direct assay
1-phosphatidylinositol 4-kinase activity	MF	direct assay
14-3-3 protein binding	MF	direct assay

Protein interactions and networks

IntAct

Human interaction partners of PI4KB in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
YWHAQ	physical association	0.900	3
YWHAB	physical association	0.860	2
YWHAG	physical association	0.860	2
ACBD3	physical association	0.540	4
NS	physical association	0.510	2
RDM1	physical association	0.400	1
SFN	physical association	0.400	1
UTRN	physical association	0.400	1
E6	physical association	0.370	1
MYCBP2	physical association	0.370	1
CBY1	physical association	0.000	1
RAB3IP	physical association	0.000	1

BioGRID (102 interactions; top human partners by supporting records): YWHAB (Affinity Capture-MS; 5 records), YWHAG (Affinity Capture-MS; 5 records), YWHAQ (Affinity Capture-MS; 5 records), NCS1 (Affinity Capture-Western; 4 records), CASP1 (Affinity Capture-MS; 3 records), CDK7 (Affinity Capture-MS; 3 records), KBTBD7 (Affinity Capture-MS; 3 records), RAB11A (Proximity Label-MS; 3 records), RDM1 (Affinity Capture-MS; 3 records), YWHAH (Affinity Capture-MS; 3 records), ARL5A (Proximity Label-MS; 2 records), ARL5B (Proximity Label-MS; 2 records), DNAJC10 (Affinity Capture-MS; 2 records), GGA2 (Reconstituted Complex; 2 records), RAB11B (Affinity Capture-MS; 2 records)

SIGNOR signaling

6 signaling interactions:

A	Effect	B	Mechanism
PRKD1	up-regulates	PI4KB	phosphorylation
PRKD2	up-regulates	PI4KB	phosphorylation
STK38	“up-regulates activity”	PI4KB	phosphorylation
NCS1	“up-regulates activity”	PI4KB
PI4KB	“up-regulates quantity”	“phosphatidylinositol 4-phosphate”	“chemical modification”
PI4KB	up-regulates	“Receptor_mediated_ endocytosis”

Disease & clinical

Genetic variants

Variant evidence for PI4KB: 102 ClinVar records (4 pathogenic / likely pathogenic); 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	66
Likely benign	7
Benign	0

Top pathogenic / likely-pathogenic (4)

Showing all 4 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
2443951	NM_001369623.2(PI4KB):c.1346T>G (p.Val449Gly)	Pathogenic	no assertion criteria provided	1
2443952	NM_001369623.2(PI4KB):c.2044G>A (p.Glu682Lys)	Pathogenic	no assertion criteria provided	1
2443953	NM_001369623.2(PI4KB):c.2261T>G (p.Met754Arg)	Pathogenic	no assertion criteria provided	1
2443954	NM_001369623.2(PI4KB):c.362A>G (p.Gln121Arg)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore PI4KB’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; 30 predictions of 1,173):

Position(s)	Effect	Δscore	Sites
1:151294016–151294017	donor_loss	1.0000	5
1:151294139	acceptor_gain	1.0000
1:151294394	donor_gain	1.0000
1:151294407–151294408	donor_loss	1.0000	4
1:151294542–151294543	acceptor_loss	1.0000	5
1:151294555	acceptor_gain	1.0000
1:151298806–151298807	donor_loss	1.0000	5
1:151301842–151301843	donor_loss	1.0000	4
1:151301968–151301969	acceptor_loss	1.0000	3
1:151301978	acceptor_gain	1.0000

AlphaMissense

3,117 missense substitutions predicted likely pathogenic (of 5,361 scored), across 629 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
M754	9	0.923	0.996
M143	9	0.916	0.998
M182	9	0.908	0.998
M718	9	0.893	0.998
M186	9	0.879	0.987
D671	8	1.000	1.000
D689	8	1.000	1.000
D568	8	0.999	1.000
H673	8	0.999	1.000
N676	8	0.999	1.000
D806	8	0.999	1.000
F134	8	0.998	1.000
F139	8	0.998	1.000
D527	8	0.997	0.999
H687	8	0.997	0.999
F703	8	0.997	1.000
H272	8	0.996	1.000
D567	8	0.996	0.999
H620	8	0.996	0.999
N162	8	0.995	0.999

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

1 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (TCGA)	favorable	0.000155

Disease associations

OMIM: gene MIM:602758 | disease phenotypes: MIM:620281

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
hearing loss, autosomal dominant 87	Limited	Autosomal dominant

Mondo (1): hearing loss, autosomal dominant 87 (MONDO:0859525)

HPO phenotypes

5 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000365	Hearing impairment
HP:0000376	Incomplete partition of the cochlea type II
HP:0003577	Congenital onset
HP:0011387	Enlarged vestibular aqueduct

GWAS associations

2 associations:

Study	Trait	p-value
GCST005951_48	Body mass index	4e-9
GCST003854_39	Gut microbiota (functional units)	2e-8

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0007874	gut microbiome measurement
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096619 (PROTEIN FAMILY), CHEMBL3268 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 356,699 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

20 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL477	ADENOSINE	4	224,426
CHEMBL2396661	ALPELISIB	4	6,400
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL554	LAPATINIB	4	70,425
CHEMBL477772	PAZOPANIB	4	16,241
CHEMBL1789941	RUXOLITINIB	4	12,161
CHEMBL2017974	BUPARLISIB	3	6,850
CHEMBL603469	LESTAURTINIB	3
CHEMBL4483575	REMIBRUTINIB	3	598
CHEMBL2165191	AZD-6482	2	974
CHEMBL4558527	AZD-8154	2	19
CHEMBL4084907	BIMIRALISIB	2	1,722
CHEMBL283403	ENVIROXIME	2	1,914
CHEMBL2041980	MMV-048	2	188
CHEMBL3586404	ONATASERTIB	2	1,138
CHEMBL521851	PICTILISIB	2	6,322
CHEMBL475251	R-406	2	787
CHEMBL384304	RG-547	2	93
CHEMBL230011	TG100-115	2	1,586
CHEMBL1090090	VX-702	2	1,085

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 22 [WO2019141694A1]	Inhibition	8.4	pIC50
torin 2	Inhibition	7.74	pIC50
PIK-93	Inhibition	7.72	pIC50
wortmannin	Inhibition	6.8	pIC50

Binding affinities (BindingDB)

377 measured of 774 human assays (783 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
CHEMBL3930509	IC50	2.4 nM
CEP-701	KD	3.4 nM
CHEMBL3958915	IC50	5.3 nM
CHEMBL2407818	IC50	5.7 nM
CHEMBL4072637	IC50	6 nM
CHEMBL6133146	IC50	6 nM
CHEMBL6150125	IC50	6 nM
CHEMBL5188324	IC50	6.1 nM
CHEMBL3920652	IC50	6.2 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
Staurosporine, 8	IC50	6.5 nM
CHEMBL6160285	IC50	7 nM
CHEMBL6171005	IC50	7 nM
CHEMBL6149562	IC50	7 nM
CHEMBL4202450	IC50	8 nM
CHEMBL6145562	IC50	8 nM
CHEMBL6161580	IC50	8 nM
CHEMBL6146998	IC50	8 nM
CHEMBL3939697	IC50	8.6 nM
CHEMBL1652677	IC50	10 nM
CHEMBL6144293	IC50	10 nM
CHEMBL6170967	IC50	10 nM
CHEMBL6120583	IC50	11 nM
CHEMBL5087055	IC50	12 nM
CHEMBL3959713	IC50	13 nM
CHEMBL3974986	IC50	13 nM
CHEMBL6169715	IC50	13 nM
CHEMBL3608927	IC50	14 nM
CHEMBL5092087	IC50	14 nM
N-[4-[[(2-hydroxy-1H-indol-3-yl)-phenylmethylidene]amino]phenyl]-N-methyl-2-(4-methylpiperazin-1-yl)acetamide	KI	15 nM	US-10981896: Indolinone derivatives as inhibitors of maternal embryonic leucine zipper kinase
CHEMBL1240703	KD	15 nM
CHEMBL6166398	IC50	16 nM
2-(2-Chloro-4-iodo-phenylamino)-N-cyclopropylmethoxy-3,4-difluoro-benzamide	IC50	17 nM
CHEMBL3929556	IC50	17 nM
CHEMBL6169748	IC50	17 nM
CHEMBL3781415	EC50	18 nM
CHEMBL3894217	IC50	18 nM
CHEMBL4204100	IC50	18 nM
CHEMBL4211696	IC50	18 nM
CHEMBL3948449	IC50	19 nM
CHEMBL6152862	IC50	19 nM
CHEMBL3893537	IC50	20 nM
CHEMBL3889874	IC50	22 nM
CHEMBL6167572	IC50	24 nM
CHEMBL5091438	IC50	25 nM
CHEMBL3915835	IC50	26 nM
CHEMBL3925101	IC50	27 nM
CHEMBL6148861	IC50	27 nM
CHEMBL4741511	KD	28 nM

ChEMBL bioactivities

500 potent at pChembl≥5 of 626 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.01	IC50	0.98	nM	CHEMBL3923414
8.70	IC50	2	nM	CHEMBL4205416
8.62	IC50	2.4	nM	CHEMBL3930509
8.43	Kd	3.7	nM	CHEMBL3936684
8.40	IC50	4	nM	CHEMBL4215340
8.40	IC50	4	nM	CHEMBL4205416
8.40	IC50	4	nM	CHEMBL4211696
8.40	IC50	4	nM	CHEMBL5619521
8.40	IC50	4	nM	CHEMBL5618321
8.30	IC50	5	nM	CHEMBL4206816
8.30	IC50	5	nM	CHEMBL4211181
8.30	IC50	5	nM	CHEMBL6163838
8.30	IC50	5	nM	CHEMBL6146491
8.28	IC50	5.3	nM	CHEMBL3958915
8.24	IC50	5.7	nM	CHEMBL2407818
8.22	IC50	6	nM	CHEMBL6133146
8.22	IC50	6	nM	CHEMBL6150125
8.21	IC50	6.1	nM	CHEMBL3976651
8.21	IC50	6.2	nM	CHEMBL3920652
8.21	Kd	6.1	nM	CHEMBL3974986
8.21	IC50	6.1	nM	CHEMBL5188324
8.15	IC50	7	nM	CHEMBL4215244
8.15	IC50	7	nM	CHEMBL4203566
8.15	IC50	7	nM	CHEMBL6160285
8.15	IC50	7	nM	CHEMBL6171005
8.15	IC50	7	nM	CHEMBL6149562
8.14	IC50	7.23	nM	CHEMBL3911522
8.10	IC50	8	nM	CHEMBL4203041
8.10	IC50	8	nM	CHEMBL4202450
8.10	IC50	8	nM	CHEMBL4209793
8.10	IC50	8	nM	CHEMBL2397317
8.10	IC50	8	nM	CHEMBL4215340
8.10	IC50	8	nM	CHEMBL6145562
8.10	IC50	8	nM	CHEMBL6161580
8.10	IC50	8	nM	CHEMBL6146998
8.10	IC50	8	nM	CHEMBL1233882
8.07	IC50	8.6	nM	CHEMBL3939697
8.05	IC50	9	nM	CHEMBL3957128
8.05	IC50	9	nM	CHEMBL4207851
8.00	IC50	10	nM	CHEMBL1652677
8.00	IC50	10	nM	AZD-6482
8.00	IC50	10	nM	CHEMBL6144293
8.00	IC50	10	nM	CHEMBL6170967
7.96	IC50	11	nM	CHEMBL4210308
7.96	IC50	11	nM	CHEMBL4211181
7.96	IC50	11	nM	CHEMBL6120583
7.90	IC50	12.5	nM	CHEMBL3959713
7.90	IC50	12.5	nM	CHEMBL1229535
7.89	IC50	13	nM	CHEMBL4215244
7.89	IC50	13	nM	CHEMBL6169715

PubChem BioAssay actives

447 with measured affinity, of 1043 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-[2-[[6-chloro-3-(4-methoxy-3-morpholin-4-ylsulfonylphenyl)-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0010	uM
4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0020	uM
N-[2-[[6-chloro-3-[3-(dimethylsulfamoyl)-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0024	uM
N-[(1-benzyltriazol-4-yl)methyl]-5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxybenzenesulfonamide	1324687: Binding affinity to 6xHisGB1 tagged PI4KB (unknown origin) expressed in Escherichia coli BL21 Star by fluorescence anisotropy based method	kd	0.0037	uM
2-fluoro-4-[2-methyl-7-[(3-methylsulfonylphenyl)methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]phenol	2128441: Inhibition of Phosphatidylinositol 4-Kinase III beta (unknown origin) preincubated for 10 min followed by incubated with ATP for 1 hr by ADP-Glo kinase assay	ic50	0.0040	uM
4-[2,5-dimethyl-7-[(3-methylsulfonylphenyl)methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]-2-fluorophenol	2128441: Inhibition of Phosphatidylinositol 4-Kinase III beta (unknown origin) preincubated for 10 min followed by incubated with ATP for 1 hr by ADP-Glo kinase assay	ic50	0.0040	uM
(3S)-4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0040	uM
4-[4-chloro-3-(methylcarbamoyl)phenyl]-N-[(3-pyrazol-1-ylphenyl)methyl]pyridine-2-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0040	uM
tert-butyl N-[2-[[5-[2-(hexanoylamino)-4-methyl-1,3-thiazol-5-yl]-2-methoxyphenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0050	uM
tert-butyl N-[2-[[2-methoxy-5-[4-methyl-2-(6-oxoheptanoylamino)-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0050	uM
4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methylphenyl)piperazine-1-carboxamide	1381468: Inhibition of PI4K3beta in human PBMC assessed as reduction in mitomycin-C treated human RPMI1788 cells-stimulated lymphocyte proliferation by measuring reduction in [3H]thymidine incorporation preincubated for 5 days followed by [3H]thymidine addition measured after 18 hrs by liquid scintillation counting method	ic50	0.0050	uM
(3S)-4-(6-amino-1-methylpyrazolo[5,4-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381533: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system	ic50	0.0050	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-(1-hydroxybutan-2-yl)-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0053	uM
2-fluoro-4-[2-methyl-8-[(3-methylsulfonylphenyl)methylamino]imidazo[1,2-a]pyrazin-3-yl]phenol	1876214: Inhibition of PI4KIIIbeta (unknown origin)	ic50	0.0057	uM
tert-butyl N-[2-[[5-[2-(heptanoylamino)-4-methyl-1,3-thiazol-5-yl]-2-methoxyphenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0060	uM
tert-butyl N-[2-[[2-methoxy-5-[4-methyl-2-(pentanoylamino)-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0060	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-(2-hydroxyethyl)-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0061	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxy-N-prop-2-ynylbenzenesulfonamide	1324687: Binding affinity to 6xHisGB1 tagged PI4KB (unknown origin) expressed in Escherichia coli BL21 Star by fluorescence anisotropy based method	kd	0.0061	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-ethyl-2-hydroperoxybenzenesulfonamide	1876214: Inhibition of PI4KIIIbeta (unknown origin)	ic50	0.0061	uM
1-[5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxyphenyl]sulfonylpiperidin-4-ol	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0062	uM
(3S)-4-(2-aminothieno[2,3-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0070	uM
(3S)-4-(6-amino-[1,2]thiazolo[5,4-d]pyrimidin-4-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0070	uM
tert-butyl N-[2-[[5-[2-(3,3-dimethylbutanoylamino)-4-methyl-1,3-thiazol-5-yl]-2-methoxyphenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0070	uM
tert-butyl N-[2-[[2-chloro-5-[4-methyl-2-(pentanoylamino)-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0070	uM
tert-butyl N-[2-[[5-[2-(hexanoylamino)-4-methyl-1,3-thiazol-5-yl]-2-methoxybenzoyl]amino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0070	uM
N-[2-[[6-chloro-3-[3-(1-hydroxybutan-2-ylsulfamoyl)-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0072	uM
(3S)-4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0080	uM
(3S)-4-(2-amino-9-methylpurin-6-yl)-N-(4-methoxy-2-methylphenyl)-3-methylpiperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0080	uM
tert-butyl N-[2-[[2-chloro-5-[2-(hexanoylamino)-4-methyl-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0080	uM
tert-butyl N-[2-[[2-methoxy-5-[4-methyl-2-(4-methylpentanoylamino)-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0080	uM
tert-butyl N-[2-[[2-chloro-5-[2-(3,3-dimethylbutanoylamino)-4-methyl-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0080	uM
1-propan-2-yl-3-quinolin-6-ylpyrazolo[3,4-d]pyrimidin-4-amine	507078: Inhibition of recombinant PI4Kbeta by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0080	uM
3-(3,4-dimethoxyphenyl)-2,5-dimethyl-N-(2-morpholin-4-ylethyl)pyrazolo[1,5-a]pyrimidin-7-amine	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0080	uM
N-[2-chloro-5-[2,5-dimethyl-7-[(2-methyl-4-pyridinyl)methylamino]pyrazolo[1,5-a]pyrimidin-3-yl]phenyl]methanesulfonamide	1381468: Inhibition of PI4K3beta in human PBMC assessed as reduction in mitomycin-C treated human RPMI1788 cells-stimulated lymphocyte proliferation by measuring reduction in [3H]thymidine incorporation preincubated for 5 days followed by [3H]thymidine addition measured after 18 hrs by liquid scintillation counting method	ic50	0.0080	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxy-N-prop-2-enylbenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0086	uM
5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N-[2-(dimethylamino)ethyl]-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0090	uM
4-(5-amino-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxy-2-methylphenyl)piperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0090	uM
tert-butyl N-[2-[[5-[2-(butanoylamino)-4-methyl-1,3-thiazol-5-yl]-2-methoxyphenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0100	uM
tert-butyl N-[2-[[5-[2-(butylcarbamoylamino)-4-methyl-1,3-thiazol-5-yl]-2-methoxyphenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0100	uM
1-[4-(5-amino-2-pyridin-3-yl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)piperazin-1-yl]-2-(4-chlorophenoxy)ethanone	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0100	uM
4-(5-amino-2-phenyl-[1,3]thiazolo[5,4-d]pyrimidin-7-yl)-N-(4-methoxyphenyl)piperazine-1-carboxamide	1381469: Inhibition of recombinant human full length GST-tagged PI4K3beta expressed in baculovirus expression system using PI lipid kinase substrate after 60 mins by ADP-Glo assay	ic50	0.0110	uM
tert-butyl N-[2-[[2-methoxy-5-[4-methyl-2-(5-methylhexanoylamino)-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0110	uM
3-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-N,N-dimethylbenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0125	uM
N-[5-[4-chloro-3-(2-hydroxyethylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]acetamide	2264893: Inhibition of human PI4Kbeta in presence of ATP	ic50	0.0125	uM
tert-butyl N-[2-[[2-methoxy-5-[4-methyl-2-(3-methylbutanoylamino)-1,3-thiazol-5-yl]phenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0130	uM
N-[5-[4-methoxy-3-(phenylsulfamoyl)phenyl]-4-methyl-1,3-thiazol-2-yl]-2-phenylacetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0140	uM
N-[2-[[6-chloro-3-[3-[4-(hydroxymethyl)piperidin-1-yl]sulfonyl-4-methoxyphenyl]-2-methylimidazo[1,2-b]pyridazin-8-yl]amino]ethyl]acetamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0149	uM
N-(4-aminocyclohexyl)-5-[6-chloro-8-[(2-ethyl-4-pyridinyl)methylamino]-2-methylimidazo[1,2-b]pyridazin-3-yl]-2-methoxybenzenesulfonamide	1324670: Inhibition of PI4KB (unknown origin) by ADP-Glo kinase assay	ic50	0.0157	uM
tert-butyl N-[2-[[5-(2-acetamido-4-methyl-1,3-thiazol-5-yl)-2-methoxyphenyl]sulfonylamino]ethyl]carbamate	2235024: Inhibition of PI4KIII-beta (unknown origin)	ic50	0.0160	uM
N-[5-[3-(benzenesulfonamido)-4-methoxyphenyl]-4-methyl-1,3-thiazol-2-yl]-2-(3,5-dimethoxyphenyl)acetamide	2026520: Inhibition of human recombinant GST tagged P14KIII beta incubated for 10 mins by ADP-Glo kinase method	ic50	0.0160	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, increases activity, increases expression	1
bisphenol A	affects cotreatment, decreases expression	1
coumarin	increases phosphorylation	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, decreases expression	1
Bortezomib	decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Aspirin	decreases expression	1
Caffeine	affects phosphorylation	1
Catechin	affects cotreatment, decreases expression	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	increases O-linked glycosylation, decreases activity	1
Fluorouracil	decreases expression, affects reaction	1
Indomethacin	affects cotreatment, decreases expression	1
Lead	affects splicing	1
Smoke	decreases expression	1
Tretinoin	increases expression	1
Vitamin E	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1

ChEMBL screening assays

258 unique, capped per target: 252 binding, 2 functional, 2 admet, 2 toxicity

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*
CHEMBL4622191	ADMET	Binding affinity to PIK4CB (unknown origin)	Stepwise Design of γ-Secretase Modulators with an Advanced Profile by Judicious Coordinated Structural Replacements and an Unconventional Phenyl Ring Bioisostere. — *J Med Chem*

Cellosaurus cell lines

10 cell lines: 9 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1PS	Abcam K-562 PI4KB KO	Cancer cell line	Female
CVCL_D2LD	Abcam Raji PI4KB KO	Cancer cell line	Male
CVCL_D7X2	Ubigene A-549 PI4KB KO	Cancer cell line	Male
CVCL_D8SF	Ubigene HCT 116 PI4KB KO	Cancer cell line	Male
CVCL_D9MX	Ubigene HEK293 PI4KB KO	Transformed cell line	Female
CVCL_E0KA	Ubigene HeLa PI4KB KO	Cancer cell line	Female
CVCL_F5Y7	EDITGENE PI4KB (NC_000001.11:g.151327455G>C) Point Mutation in A549 Cell Line	Cancer cell line	Male
CVCL_TD40	HAP1 PI4KB (-) 1	Cancer cell line	Male
CVCL_TD41	HAP1 PI4KB (-) 2	Cancer cell line	Male
CVCL_WQ28	Abcam Jurkat PI4KB KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for PI4KB across ~30M SureChEMBL compounds — explore on Sugi Predict.