PI4K2B

Summary

PI4K2B (phosphatidylinositol 4-kinase type 2 beta, HGNC:18215) is a protein-coding gene on chromosome 4p15.2, encoding Phosphatidylinositol 4-kinase type 2-beta (Q8TCG2). Together with PI4K2A and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell.

This gene encodes a member of the type II PI4 kinase protein family. The encoded protein is primarily cytosolic and contributes to overall PI4-kinase activity along with other protein family members. This protein is involved in early T cell activation.

Source: NCBI Gene 55300 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 70 total
• Phenotypes (HPO): 1
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_018323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18215
Approved symbol	PI4K2B
Name	phosphatidylinositol 4-kinase type 2 beta
Location	4p15.2
Locus type	gene with protein product
Status	Approved
Aliases	PI4KIIB, FLJ11105, PIK42B
Ensembl gene	ENSG00000038210
Ensembl biotype	protein_coding
OMIM	612101
Entrez	55300

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 7 protein_coding

ENST00000264864, ENST00000512921, ENST00000871538, ENST00000871539, ENST00000871540, ENST00000963199, ENST00000963200

RefSeq mRNA: 1 — MANE Select: NM_018323 NM_018323

CCDS: CCDS3433

Canonical transcript exons

ENST00000264864 — 10 exons

Exon	Start	End
ENSE00001150987	25277014	25279204
ENSE00001205657	25234033	25234431
ENSE00003672948	25252321	25252475
ENSE00003862404	25255065	25255265
ENSE00003872113	25269144	25269203
ENSE00003883088	25256543	25256674
ENSE00003884573	25260524	25260591
ENSE00003886372	25268443	25268576
ENSE00003886487	25263750	25263849
ENSE00003887927	25259037	25259190

Expression profiles

Bgee: expression breadth ubiquitous, 234 present calls, max score 94.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.9115 / max 473.9439, expressed in 1812 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
47124	21.4602	1811
47122	3.4967	1316
47125	1.4513	686

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	94.66	gold quality
jejunal mucosa	UBERON:0000399	94.51	gold quality
duodenum	UBERON:0002114	92.85	gold quality
upper arm skin	UBERON:0004263	92.01	gold quality
ileal mucosa	UBERON:0000331	91.58	gold quality
epithelium of nasopharynx	UBERON:0001951	90.77	gold quality
oocyte	CL:0000023	89.18	gold quality
liver	UBERON:0002107	89.12	gold quality
epithelial cell of pancreas	CL:0000083	88.57	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.52	gold quality
rectum	UBERON:0001052	88.33	gold quality
calcaneal tendon	UBERON:0003701	87.62	gold quality
right lobe of liver	UBERON:0001114	87.50	gold quality
gingival epithelium	UBERON:0001949	87.20	gold quality
bone marrow cell	CL:0002092	86.70	gold quality
tonsil	UBERON:0002372	86.57	gold quality
nasal cavity mucosa	UBERON:0001826	86.46	gold quality
gingiva	UBERON:0001828	86.43	gold quality
esophagus squamous epithelium	UBERON:0006920	86.37	gold quality
islet of Langerhans	UBERON:0000006	85.79	gold quality
bronchial epithelial cell	CL:0002328	85.74	gold quality
adrenal tissue	UBERON:0018303	85.59	gold quality
bronchus	UBERON:0002185	85.41	gold quality
nasal cavity epithelium	UBERON:0005384	85.15	gold quality
amniotic fluid	UBERON:0000173	85.09	gold quality
cardia of stomach	UBERON:0001162	85.09	gold quality
saliva-secreting gland	UBERON:0001044	85.06	gold quality
minor salivary gland	UBERON:0001830	84.88	gold quality
mouth mucosa	UBERON:0003729	84.86	gold quality
endometrium	UBERON:0001295	84.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.88

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

153 targeting PI4K2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753

Literature-anchored findings (GeneRIF, showing 10)

• Type II PtdIns 4-kinase beta interacts with TCR-CD3 zeta chain. The C-terminal ITAM is critical for enzyme docking on the zeta chain. The association is tyrosyl phosphorylation dependent. Mutation of Y-151 & Y-142 disrupts interaction of the 2 proteins. (PMID:16337488)
• UV irradiation increases nuclear PtdIns5P levels via inhibition of the activity of the beta isoform of PtdIns5P 4-kinase (PIP4Kbeta), an enzyme that can phosphorylate and remove PtdIns5P. (PMID:16949365)
• LB-PI4K2B-1S-specific CD4(+) T cells contributed to the antitumor response by both directly eliminating malignant cells as effector cells and stimulating CD8(+) T cell immunity as helper cells. (PMID:18316730)
• There is no evidence to suggest that PI4K2B is contributing to bipolar disorder in this family but a role for this gene in schizophrenia has not been excluded. (PMID:19539307)
• PIP4Kbeta interacts with and modulates nuclear localization of the PIP4Kalpha. (PMID:20583997)
• type II PtdIns 4-kinase beta is a key component in early T cell activation signaling cascades (PMID:23619705)
• Canonical tyrosine residues mutation in FcepsilonRIgamma ITAM (Y65 and Y76) reveals that these two tyrosine residues in gamma subunit are required for its interaction with type II PtdIns 4-kinases. (PMID:24481753)
• Results provide evidence that type II PtdIns 4-kinase b was indeed recruited to CD4- p56lck complex upon CD4 receptor cross linking, suggests a mechanism for its association and a role for it in CD4-mediated intracellular calcium release. (PMID:24972704)
• Here two crystal structures are presented: the structure of human PIK42A and the structure of PIK42B containing a nucleoside analogue. (PMID:26143926)
• RNA interference of the type II phosphatidylinositol 4-kinases PI4KIIa and PI4KIIa in primary human endothelial cells leads to formation of an increased proportion of short WPB with perturbed packing of VWF, as exemplified by increased exposure of antibody-binding sites. (PMID:27068535)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	pi4k2b	ENSDARG00000013881
mus_musculus	Pi4k2b	ENSMUSG00000029186
rattus_norvegicus	Pi4k2b	ENSRNOG00000003924
drosophila_melanogaster	Pi4KIIalpha	FBGN0037339
caenorhabditis_elegans		WBGENE00022501

Paralogs (1): PI4K2A (ENSG00000155252)

Protein

Protein identifiers

Phosphatidylinositol 4-kinase type 2-beta — Q8TCG2 (reviewed: Q8TCG2)

Alternative names: Phosphatidylinositol 4-kinase type II-beta

All UniProt accessions (2): G5E9Z4, Q8TCG2

UniProt curated annotations — full annotation on UniProt →

Function. Together with PI4K2A and the type III PI4Ks (PIK4CA and PIK4CB) it contributes to the overall PI4-kinase activity of the cell. This contribution may be especially significant in plasma membrane, endosomal and Golgi compartments. The phosphorylation of phosphatidylinositol (PI) to PI4P is the first committed step in the generation of phosphatidylinositol 4,5-bisphosphate (PIP2), a precursor of the second messenger inositol 1,4,5-trisphosphate (InsP3). Contributes to the production of InsP3 in stimulated cells and is likely to be involved in the regulation of vesicular trafficking.

Subcellular location. Cytoplasm. Cytosol. Golgi apparatus membrane. Endoplasmic reticulum membrane. Cell membrane. Early endosome membrane.

Tissue specificity. Widely expressed.

Activity regulation. Inhibited by phenylarsine oxide and adenosine. Activation through membrane association is stimulated by active RAC1.

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

RefSeq proteins (1): NP_060793* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000403	PI3/4_kinase_cat_dom	Domain
IPR039756	Lsb6/PI4K2	Family

Pfam: PF00454

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), 1 shown:

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

UniProt features (46 total): helix 14, region of interest 8, strand 8, binding site 5, modified residue 3, compositionally biased region 2, turn 2, chain 1, domain 1, sequence variant 1, mutagenesis site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
4WTV	X-RAY DIFFRACTION	1.9
9HHM	X-RAY DIFFRACTION	2.25
8A5X	X-RAY DIFFRACTION	2.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TCG2-F1	76.63	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (5): 133; 148; 257–260; 271–272; 344

Post-translational modifications (3): 12, 17, 45

Mutagenesis-validated functional residues (1):

Position	Phenotype
304	increased localization to plasma membrane.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1483248	Synthesis of PIPs at the ER membrane
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-1660514	Synthesis of PIPs at the Golgi membrane
R-HSA-1660516	Synthesis of PIPs at the early endosome membrane

MSigDB gene sets: 229 (showing top): HORIUCHI_WTAP_TARGETS_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, WWTAAGGC_UNKNOWN, GOBP_ENDOSOME_ORGANIZATION, MODULE_255, GOBP_VESICLE_ORGANIZATION, MODULE_317, IVANOVA_HEMATOPOIESIS_MATURE_CELL, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GTGCCTT_MIR506, GOCC_TRANS_GOLGI_NETWORK

GO Biological Process (5): phosphatidylinositol biosynthetic process (GO:0006661), Golgi organization (GO:0007030), endosome organization (GO:0007032), phosphatidylinositol phosphate biosynthetic process (GO:0046854), lipid metabolic process (GO:0006629)

GO Molecular Function (5): 1-phosphatidylinositol 4-kinase activity (GO:0004430), ATP binding (GO:0005524), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): Golgi membrane (GO:0000139), endosome (GO:0005768), endoplasmic reticulum membrane (GO:0005789), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), early endosome membrane (GO:0031901), cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), Golgi apparatus (GO:0005794)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
PI Metabolism	4

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	3
cytoplasm	3
cellular anatomical structure	3
endomembrane system organization	2
intracellular membrane-bounded organelle	2
biosynthetic process	1
phosphatidylinositol metabolic process	1
organelle organization	1
vesicle organization	1
glycerophospholipid biosynthetic process	1
primary metabolic process	1
phosphatidylinositol kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
Golgi apparatus	1
bounding membrane of organelle	1
cytoplasmic vesicle	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
Golgi apparatus subcompartment	1
membrane	1
cell periphery	1
early endosome	1
endosome membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

638 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PI4K2B	PI4KB	P78405	832
PI4K2B	PI4KA	P42356	764
PI4K2B	EEA1	Q15075	745
PI4K2B	HLA-DQB1	P01917	578
PI4K2B	OSBP	P22059	547
PI4K2B	SERPINA4	P29622	479
PI4K2B	PIP5K1C	O60331	471
PI4K2B	EEF1A2	P54266	465
PI4K2B	IMPA2	O14732	437
PI4K2B	SYNJ1	O43426	431
PI4K2B	GNG13	Q9P2W3	422
PI4K2B	NIPAL4	Q0D2K0	416
PI4K2B	PIKFYVE	Q9Y2I7	413
PI4K2B	STX8	Q9UNK0	411
PI4K2B	BTG3	Q14201	409

IntAct

69 interactions, top by confidence:

A	B	Type	Score
TRIP13	INTS11	psi-mi:“MI:0914”(association)	0.550
MANSC1	KLRG2	psi-mi:“MI:0914”(association)	0.530
HAVCR2	TCAF2	psi-mi:“MI:0914”(association)	0.530
EFNB2	FAM171A2	psi-mi:“MI:0914”(association)	0.530
SPINT2	UPK3BL1	psi-mi:“MI:0914”(association)	0.530
KBTBD4	KPNA5	psi-mi:“MI:0914”(association)	0.530
GFOD1	PER1	psi-mi:“MI:0914”(association)	0.530
SLC31A1	C2orf72	psi-mi:“MI:0914”(association)	0.530
PSME1	POLR3A	psi-mi:“MI:0914”(association)	0.530
PLAUR	XRCC3	psi-mi:“MI:0914”(association)	0.530
ZNRD2	MYO9A	psi-mi:“MI:0914”(association)	0.530
PI4K2B		psi-mi:“MI:0915”(physical association)	0.370
PI4K2B	DDX60L	psi-mi:“MI:0914”(association)	0.350
ZNRD2	KRBA1	psi-mi:“MI:0914”(association)	0.350
PLAUR	DDX11L8	psi-mi:“MI:0914”(association)	0.350
SIRT6	HDAC3	psi-mi:“MI:0914”(association)	0.350
GATD1		psi-mi:“MI:0914”(association)	0.350
TRIP13	METTL8	psi-mi:“MI:0914”(association)	0.350
HDAC10	GNPAT	psi-mi:“MI:0914”(association)	0.350
GMPPB	PRMT3	psi-mi:“MI:0914”(association)	0.350
PPP4R1L	IFT56	psi-mi:“MI:0914”(association)	0.350
HCST	TMEM120B	psi-mi:“MI:0914”(association)	0.350
FTL	SH3PXD2B	psi-mi:“MI:0914”(association)	0.350
MAGEA9	CIBAR1	psi-mi:“MI:0914”(association)	0.350
BBS7	TARS3	psi-mi:“MI:0914”(association)	0.350

BioGRID (88): PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS), PI4K2B (Affinity Capture-MS)

ESM2 similar proteins: A5D791, C0SV12, C6L7U1, D1FP57, F4HP88, F4I6G4, F4I7C7, F4JBP3, F4K6D3, F4KIX0, O22199, O64752, Q0WMZ6, Q336N8, Q5SNL7, Q5W6L9, Q5XVJ4, Q6AUQ7, Q6NPP4, Q6NQ79, Q7X7H4, Q7X9B9, Q7XIT1, Q8GSA7, Q8GUI6, Q8GUL1, Q8GXC6, Q8H111, Q8TCG2, Q8W4R8, Q9C5Q8, Q9C5S2, Q9C671, Q9C6G0, Q9C951, Q9C9U5, Q9CA74, Q9FNF8, Q9FYG2, Q9LE38

Diamond homologs: P42951, Q08B31, Q28G26, Q2TBE6, Q49GP5, Q505I0, Q5XIL2, Q5ZIK0, Q6DCQ8, Q6PE18, Q8CBQ5, Q8TCG2, Q99M64, Q9BTU6, Q9UT42, Q6K881, Q9C671, Q9SI52

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
PI4K2B	“down-regulates quantity”	1-phosphatidyl-1D-myo-inositol(1-)	“chemical modification”
PI4K2B	“down-regulates quantity”	ATP(4-)	“chemical modification”
PI4K2B	“up-regulates quantity”	“1-phosphatidyl-1D-myo-inositol 4-phosphate”	“chemical modification”
PI4K2B	“up-regulates quantity”	ADP(3-)	“chemical modification”
adenosine	“down-regulates activity”	PI4K2B	“chemical inhibition”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	54
Likely benign	4
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2419 predictions. Top by Δscore:

Variant	Effect	Δscore
4:25252314:A:AG	acceptor_gain	1.0000
4:25252317:GCAGT:G	acceptor_loss	1.0000
4:25252318:CAGT:C	acceptor_loss	1.0000
4:25252318:CAGTA:C	acceptor_loss	1.0000
4:25252319:A:AG	acceptor_gain	1.0000
4:25252319:A:G	acceptor_loss	1.0000
4:25252320:G:GA	acceptor_gain	1.0000
4:25252320:GT:G	acceptor_gain	1.0000
4:25252320:GTA:G	acceptor_gain	1.0000
4:25252320:GTAA:G	acceptor_gain	1.0000
4:25252320:GTAAC:G	acceptor_gain	1.0000
4:25252447:G:GT	donor_gain	1.0000
4:25252464:GATCC:G	donor_gain	1.0000
4:25252472:GAGG:G	donor_gain	1.0000
4:25252474:GG:G	donor_gain	1.0000
4:25252475:GG:G	donor_gain	1.0000
4:25252475:GGT:G	donor_loss	1.0000
4:25252476:GTG:G	donor_loss	1.0000
4:25252477:T:G	donor_loss	1.0000
4:25255057:T:A	acceptor_gain	1.0000
4:25255057:T:TA	acceptor_gain	1.0000
4:25255061:CTAG:C	acceptor_loss	1.0000
4:25255062:TA:T	acceptor_loss	1.0000
4:25255063:A:AG	acceptor_gain	1.0000
4:25255063:A:G	acceptor_loss	1.0000
4:25255064:G:GA	acceptor_gain	1.0000
4:25255064:GA:G	acceptor_gain	1.0000
4:25255064:GAA:G	acceptor_gain	1.0000
4:25255064:GAAA:G	acceptor_gain	1.0000
4:25255064:GAAAA:G	acceptor_gain	1.0000

AlphaMissense

3182 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:25263802:A:C	D344A	1.000
4:25263802:A:T	D344V	1.000
4:25268454:T:A	W364R	1.000
4:25268454:T:C	W364R	1.000
4:25252443:A:C	S131R	0.999
4:25252445:T:A	S131R	0.999
4:25252445:T:G	S131R	0.999
4:25252447:G:A	G132E	0.999
4:25252449:A:C	S133R	0.999
4:25252451:T:A	S133R	0.999
4:25252451:T:G	S133R	0.999
4:25255083:A:G	K148E	0.999
4:25255085:A:C	K148N	0.999
4:25255085:A:T	K148N	0.999
4:25255087:C:A	P149H	0.999
4:25259182:G:C	R301T	0.999
4:25259182:G:T	R301I	0.999
4:25259183:A:C	R301S	0.999
4:25259183:A:T	R301S	0.999
4:25259186:T:A	N302K	0.999
4:25259186:T:G	N302K	0.999
4:25260527:G:T	R305M	0.999
4:25260528:G:C	R305S	0.999
4:25260528:G:T	R305S	0.999
4:25260541:T:A	W310R	0.999
4:25260541:T:C	W310R	0.999
4:25263803:T:A	D344E	0.999
4:25263803:T:G	D344E	0.999
4:25268456:G:C	W364C	0.999
4:25268456:G:T	W364C	0.999

dbSNP variants (sampled 300 via entrez): RS1000015693 (4:25242689 T>A), RS1000031805 (4:25235236 T>C), RS1000076343 (4:25266223 A>C,T), RS1000133512 (4:25246472 C>A,G,T), RS1000169176 (4:25264729 G>A), RS1000199882 (4:25264500 A>G), RS1000207554 (4:25260696 A>G), RS1000378753 (4:25249434 C>G,T), RS10004160 (4:25253961 G>A,C), RS1000479003 (4:25276719 G>C), RS1000484545 (4:25246677 G>A), RS1000521974 (4:25239102 T>C), RS10005278 (4:25236136 A>T), RS1000529130 (4:25243927 G>A), RS1000632020 (4:25243546 G>A)

Disease associations

OMIM: gene MIM:612101 | disease phenotypes: MIM:209850

GenCC curated gene-disease

Mondo (1): autism (MONDO:0005260)

Orphanet (0):

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST003465_14	Cannabis dependence symptom count	5.000000e-06
GCST003465_3	Cannabis dependence symptom count	6.000000e-08
GCST006916_7	Attention deficit hyperactivity disorder	1.000000e-06
GCST007005_2	Logical memory (immediate recall) in normal cognition	1.000000e-07
GCST011155_23	Nontraumatic osteonecrosis of the femoral head	8.000000e-06

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0008457	cannabis dependence measurement
EFO:0004874	memory performance
EFO:1001930	idiopathic osteonecrosis of the femoral head

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096619 (PROTEIN FAMILY), CHEMBL3220 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 222,014 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL477	ADENOSINE	4	222,014

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol kinases

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

Ligand	Action	Affinity	Parameter
adenosine	Inhibition	5.0	pIC50

ChEMBL bioactivities

15 potent at pChembl≥5 of 79 total, top 15 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.43	Ki	3700	nM	CHEMBL63783
5.39	Ki	4100	nM	CHEMBL293027
5.30	Ki	5000	nM	CHEMBL413106
5.30	Ki	5000	nM	CHEMBL62835
5.22	IC50	6000	nM	CHEMBL293027
5.22	Ki	6000	nM	CHEMBL294590
5.22	IC50	6000	nM	CHEMBL63783
5.16	Ki	6900	nM	CHEMBL306444
5.15	IC50	7100	nM	2-AMINOPYRIDINE
5.14	IC50	7200	nM	CHEMBL413106
5.14	IC50	7200	nM	CHEMBL62835
5.08	Ki	8300	nM	CHEMBL291377
5.08	Ki	8400	nM	CHEMBL1321883
5.06	IC50	8700	nM	CHEMBL294590
5.05	Ki	9000	nM	CHEMBL304265

PubChem BioAssay actives

15 with measured affinity, of 157 total; 10 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
9-cyclohexylpurin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	3.7000	uM
9-(1-adamantyl)purin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	4.1000	uM
9-cycloheptylpurin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	5.0000	uM
9-(1-methylcyclohexyl)purin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	5.0000	uM
9-cyclopentylpurin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	6.0000	uM
9-tert-butylpurin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	6.9000	uM
pyridin-2-amine	155650: Inhibitory activity (IC50) against human phosphatidylinositol 4-kinase at the ATP binding site	ic50	7.1000	uM
9-(2-fluorophenyl)purin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	8.3000	uM
[(3aR,4R,6R,6aR)-4-(6-aminopurin-9-yl)-2,2-dimethyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methanol	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	8.4000	uM
9-(2,2-dimethylpropyl)purin-6-amine	155653: Binding affinity (Ki) against human phosphatidylinositol 4-kinase	ki	9.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	3
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation, decreases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance	2
Resveratrol	decreases activity, affects cotreatment, increases expression, affects binding	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
pirinixic acid	increases activity, affects binding, decreases expression	1
bisphenol A	affects cotreatment, decreases methylation	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
manganese chloride	increases abundance, affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Rosiglitazone	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Acetaminophen	increases expression	1
Arsenic	increases abundance, affects cotreatment, decreases expression	1
Atrazine	decreases expression	1
Benzo(a)pyrene	decreases expression	1
Cadmium	increases abundance, increases palmitoylation, decreases reaction	1
Caffeine	decreases phosphorylation	1
Cisplatin	increases expression	1

ChEMBL screening assays

31 unique, capped per target: 29 binding, 2 functional

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

Cellosaurus cell lines

7 cell lines: 6 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2AP	Abcam HeLa PI4K2B KO	Cancer cell line	Female
CVCL_D7X1	Ubigene A-549 PI4K2B KO	Cancer cell line	Male
CVCL_D8SE	Ubigene HCT 116 PI4K2B KO	Cancer cell line	Male
CVCL_D9MW	Ubigene HEK293 PI4K2B KO	Transformed cell line	Female
CVCL_E0K9	Ubigene HeLa PI4K2B KO	Cancer cell line	Female
CVCL_TD38	HAP1 PI4K2B (-) 1	Cancer cell line	Male
CVCL_TD39	HAP1 PI4K2B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism
NCT00346736	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00352248	PHASE3	COMPLETED	Randomized Controlled Trial of Acupuncture Versus Sham Acupuncture in Autistic Spectrum Disorder
NCT00352352	PHASE3	COMPLETED	Use of Acupuncture In Children With Autistic Spectrum Disorder
NCT00355329	PHASE3	COMPLETED	Randomized Control Trial of Using Tongue Acupuncture in Autistic Spectrum Disorder Using PET Scan for Clinical Correlation
NCT00498173	PHASE3	COMPLETED	Effectiveness of Atomoxetine in Treating ADHD Symptoms in Children and Adolescents With Autism
NCT00541346	PHASE3	COMPLETED	A Pilot Study of Daytrana TM in Children With Autism Co-Morbid for Attention Deficit Hyperactivity Disorder (ADHD) Symptoms