PIP5K1B

Summary

PIP5K1B (phosphatidylinositol-4-phosphate 5-kinase type 1 beta, HGNC:8995) is a protein-coding gene on chromosome 9q21.11, encoding Phosphatidylinositol 4-phosphate 5-kinase type-1 beta (O14986). Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cyto….

Predicted to enable 1-phosphatidylinositol-4-phosphate 5-kinase activity. Predicted to be involved in phosphatidylinositol phosphate biosynthetic process. Predicted to act upstream of or within phosphatidylinositol biosynthetic process. Located in uropod.

Source: NCBI Gene 8395 — RefSeq curated summary.

At a glance

• GWAS associations: 21
• Clinical variants (ClinVar): 70 total — 2 pathogenic
• Druggable target: yes
• MANE Select transcript: NM_003558

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:8995
Approved symbol	PIP5K1B
Name	phosphatidylinositol-4-phosphate 5-kinase type 1 beta
Location	9q21.11
Locus type	gene with protein product
Status	Approved
Aliases	STM7, MSS4
Ensembl gene	ENSG00000107242
Ensembl biotype	protein_coding
OMIM	602745
Entrez	8395

Gene structure

Transcript identifiers

Ensembl transcripts: 31 — 28 protein_coding, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000265382, ENST00000377284, ENST00000437200, ENST00000440050, ENST00000472907, ENST00000474356, ENST00000478500, ENST00000541509, ENST00000885666, ENST00000885667, ENST00000885668, ENST00000885669, ENST00000885670, ENST00000885671, ENST00000885672, ENST00000885673, ENST00000885674, ENST00000885675, ENST00000885676, ENST00000885677, ENST00000885678, ENST00000885679, ENST00000949884, ENST00000949885, ENST00000949886, ENST00000949887, ENST00000949888, ENST00000949889, ENST00000949890, ENST00000949891, ENST00000949892

RefSeq mRNA: 7 — MANE Select: NM_003558 NM_001278253, NM_001376036, NM_001376037, NM_001376039, NM_001376040, NM_001376041, NM_003558

CCDS: CCDS65063, CCDS6624

Canonical transcript exons

ENST00000265382 — 16 exons

Exon	Start	End
ENSE00000705556	68934890	68935045
ENSE00000705561	68940646	68940790
ENSE00000917465	68894339	68894638
ENSE00000917466	68917548	68917759
ENSE00000917467	68919479	68919562
ENSE00000917468	68919681	68919729
ENSE00000917469	68923302	68923386
ENSE00001312693	68863837	68863967
ENSE00001332769	69008447	69009176
ENSE00001332815	68818461	68818545
ENSE00001332816	68742501	68742657
ENSE00001332819	68705240	68705762
ENSE00001680325	68876677	68876794
ENSE00003670989	68991140	68991257
ENSE00003756251	68822615	68822683
ENSE00003790510	68888981	68889133

Expression profiles

Bgee: expression breadth ubiquitous, 248 present calls, max score 98.93.

FANTOM5 (CAGE): breadth broad, TPM avg 8.1353 / max 356.9954, expressed in 814 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96794	2.4024	651
96793	1.9845	596
96799	1.7376	386
96798	1.0899	356
96797	0.5192	203
96796	0.1208	65
96795	0.1122	46
96809	0.1007	13
96802	0.0448	11
96801	0.0125	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	98.93	gold quality
jejunal mucosa	UBERON:0000399	95.49	gold quality
ileal mucosa	UBERON:0000331	95.15	gold quality
colonic mucosa	UBERON:0000317	93.83	gold quality
mucosa of sigmoid colon	UBERON:0004993	93.36	gold quality
rectum	UBERON:0001052	92.19	gold quality
duodenum	UBERON:0002114	92.02	gold quality
cardiac muscle of right atrium	UBERON:0003379	91.27	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	90.82	gold quality
left ventricle myocardium	UBERON:0006566	90.08	gold quality
pigmented layer of retina	UBERON:0001782	89.89	gold quality
retina	UBERON:0000966	89.88	gold quality
parotid gland	UBERON:0001831	89.86	gold quality
myocardium	UBERON:0002349	89.54	gold quality
cerebellar cortex	UBERON:0002129	88.32	gold quality
pancreatic ductal cell	CL:0002079	88.29	gold quality
cerebellar hemisphere	UBERON:0002245	88.25	gold quality
mucosa of transverse colon	UBERON:0004991	88.15	gold quality
cerebellum	UBERON:0002037	88.11	gold quality
heart left ventricle	UBERON:0002084	88.02	gold quality
cardiac ventricle	UBERON:0002082	87.79	gold quality
bone marrow cell	CL:0002092	87.44	gold quality
blood vessel layer	UBERON:0004797	87.29	gold quality
trabecular bone tissue	UBERON:0002483	87.22	gold quality
cardiac atrium	UBERON:0002081	86.90	gold quality
lower lobe of lung	UBERON:0008949	86.88	gold quality
heart	UBERON:0000948	86.87	gold quality
secondary oocyte	CL:0000655	86.82	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.79	gold quality
right atrium auricular region	UBERON:0006631	86.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	yes	161.30
E-CURD-119	yes	21.29
E-ANND-3	yes	16.32
E-HCAD-25	yes	7.53

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

87 targeting PIP5K1B, 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-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4283	100.00	66.42	2097
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-432-3P	100.00	67.86	705
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-146A-5P	99.96	68.93	988
HSA-MIR-146B-5P	99.96	69.13	977
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-7153-5P	99.94	68.89	1006
HSA-MIR-450B-5P	99.92	71.48	3175
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-4753-3P	99.90	71.03	3786

Literature-anchored findings (GeneRIF, showing 7)

• findings show that the human type I phosphatidylinositol 4-phosphate 5-kinase isoform beta (PIPKIbeta) has a role in organizing signaling at the cell rear (PMID:18158329)
• Syk-dependent phosphorylation of PIP5K1B is the dominant modification responsible for the decrease in cellular phosphatidylinositol 4,5-bisphosphate. (PMID:19553680)
• Results identify an isoform-specific PDZ-binding motif in PIP5KIbeta, which confers specificity for PIP5KIbeta signaling at the uropod during leukocyte chemotaxis. (PMID:20442317)
• Results identify PIPKIbeta as a novel regulator of focal adhesion disassembly and suggest that PIPKIbeta spatially regulates beta1 integrin endocytosis at adhesion sites to control cell migration. (PMID:20624912)
• Knockdown of PIP5K1B in fibroblasts reproduced abnormal actin cytoskeleton remodeling evidenced in Friedreich’s ataxia patient cells. (PMID:23552101)
• Data indicate that type I phosphatidylinositol 4-phosphate 5-kinase PIP5KIbeta mutants whose dimerization was impaired showed a severe decrease in PI(4,5)P2 production and plasma membrane delocalization. (PMID:25713054)
• LRRC8A as a central mediator promotes colon cancer metastasis by regulating PIP5K1B/PIP2 pathway. (PMID:38350542)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	pip5k1bb	ENSDARG00000006508
danio_rerio	pip5k1ba	ENSDARG00000044295
mus_musculus	Pip5k1b	ENSMUSG00000024867
rattus_norvegicus	Pip5k1b	ENSRNOG00000015232

Paralogs (6): PIP5K1A (ENSG00000143398), PIP4K2A (ENSG00000150867), PIP4K2C (ENSG00000166908), PIP5KL1 (ENSG00000167103), PIP5K1C (ENSG00000186111), PIP4K2B (ENSG00000276293)

Protein

Protein identifiers

Phosphatidylinositol 4-phosphate 5-kinase type-1 beta — O14986 (reviewed: O14986)

Alternative names: Phosphatidylinositol 4-phosphate 5-kinase type I beta, Protein STM-7, Type I phosphatidylinositol 4-phosphate 5-kinase beta

All UniProt accessions (4): O14986, A0A0A0MRU3, A0A0A0MSP5, A0A0A0MT25

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns(4)P/PI4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2/PIP2), a lipid second messenger that regulates several cellular processes such as signal transduction, vesicle trafficking, actin cytoskeleton dynamics, cell adhesion, and cell motility. PtdIns(4,5)P2 can directly act as a second messenger or can be utilized as a precursor to generate other second messengers: inositol 1,4,5-trisphosphate (IP3), diacylglycerol (DAG) or phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3/PIP3). Mediates RAC1-dependent reorganization of actin filaments. Contributes to the activation of phospholipase PLD2. Together with PIP5K1A, is required, after stimulation by G-protein coupled receptors, for the synthesis of IP3 that will induce stable platelet adhesion.

Subunit / interactions. Interacts with RAC1, AJUBA, PLD1, PLD2 and ARF1.

Subcellular location. Cytoplasm. Cytosol. Cell membrane. Endomembrane system.

Tissue specificity. Detected in heart, pancreas, brain, kidney, skeletal muscle and lung.

Isoforms (3)

UniProt ID	Names	Canonical?
O14986-1	1	yes
O14986-2	2, Isoform 1
O14986-3	3

RefSeq proteins (7): NP_001265182, NP_001362965, NP_001362966, NP_001362968, NP_001362969, NP_001362970, NP_003549* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002498	PInositol-4-P-4/5-kinase_core	Domain
IPR023610	PInositol-4/5-P-5/4-kinase	Family
IPR027483	PInositol-4-P-4/5-kinase_C_sf	Homologous_superfamily
IPR027484	PInositol-4-P-5-kinase_N	Homologous_superfamily

Pfam: PF01504

Enzyme classification (BRENDA):

• EC 2.7.1.68 — 1-phosphatidylinositol-4-phosphate 5-kinase (BRENDA: 15 organisms, 50 substrates, 41 inhibitors, 41 Km, 0 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
1-PHOSPHATIDYL-1D-MYO-INOSITOL 4-PHOSPHATE	0.0012–4.1	14
ATP	0.002–0.2	13
1-STEAROYL-2-ARACHIDONOYL PHOSPHATIDYL-1D-MYO-IN	4.9–16	3
1-STEAROYL-2-OLEOYL PHOSPHATIDYL-1D-MYO-INOSITOL	1.6–3.7	3
1-PHOSPHATIDYL-1D-MYO-INOSITOL 3-PHOSPHATE	0.005–0.065	2
PHOSPHATIDYLINOSITOL 3,4-BISPHOSPHATE	0.006–0.08	2
GTP	0.133	1
PHOSPHATIDYLINOSITOL 3-PHOSPHATE	0.12	1

Catalyzed reactions (Rhea), 7 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol 4-phosphate) + ATP = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + ADP + H(+) (RHEA:14425)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ADP + H(+) (RHEA:40363)
• 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol 4-phosphate + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol 4,5-bisphosphate + ADP + H(+) (RHEA:40367)
• 1-octadecanoyl-2-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phospho-(1D-myo-inositol) + ATP = 1-octadecanoyl-2-(5Z,8Z,11Z,14Z)-eicosatetraenoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40375)
• 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol + ATP = 1-octadecanoyl-2-(9Z)-octadecenoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40379)
• 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol + ATP = 1-octadecanoyl-2-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40383)
• 1,2-di-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol + ATP = 1,2-di(9Z,12Z)-octadecadienoyl-sn-glycero-3-phospho-1D-myo-inositol 5-phosphate + ADP + H(+) (RHEA:40387)

UniProt features (11 total): modified residue 3, splice variant 3, chain 1, domain 1, sequence conflict 1, region of interest 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O14986-F1	70.02	0.49

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 (3): 445, 447, 448

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1660499	Synthesis of PIPs at the plasma membrane
R-HSA-201688	WNT mediated activation of DVL
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling

MSigDB gene sets: 248 (showing top): BIOCARTA_RHO_PATHWAY, GGGACCA_MIR133A_MIR133B, ZHAN_LATE_DIFFERENTIATION_GENES_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, MAHADEVAN_IMATINIB_RESISTANCE_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GGGTGGRR_PAX4_03, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, RODRIGUES_NTN1_TARGETS_DN, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, PID_RHOA_PATHWAY, GOBP_GLYCEROLIPID_METABOLIC_PROCESS

GO Biological Process (6): phosphatidylinositol biosynthetic process (GO:0006661), phosphatidylinositol phosphate biosynthetic process (GO:0046854), regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051896), lipid metabolic process (GO:0006629), regulation of signal transduction (GO:0009966), phosphatidylinositol metabolic process (GO:0046488)

GO Molecular Function (9): 1-phosphatidylinositol-3-phosphate 5-kinase activity (GO:0000285), ATP binding (GO:0005524), 1-phosphatidylinositol-4-phosphate 5-kinase activity (GO:0016308), phosphatidylinositol kinase activity (GO:0052742), 1-phosphatidylinositol-5-kinase activity (GO:0052810), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (6): uropod (GO:0001931), cytosol (GO:0005829), plasma membrane (GO:0005886), endomembrane system (GO:0012505), cytoplasm (GO:0005737), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
PI Metabolism	1
TCF dependent signaling in response to WNT	1
Negative regulation of the PI3K/AKT network	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
phosphatidylinositol kinase activity	3
biosynthetic process	1
phosphatidylinositol metabolic process	1
glycerophospholipid biosynthetic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of intracellular signal transduction	1
primary metabolic process	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
phosphorus metabolic process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
lipid kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cell trailing edge	1
plasma membrane bounded cell projection	1
cytoplasm	1
membrane	1
cell periphery	1
vacuole	1
plasma membrane	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

4 interactions, top by confidence:

A	B	Type	Score
PIP5K1B	APAF1	psi-mi:“MI:0914”(association)	0.350
MCRS1	PIP5K1B	psi-mi:“MI:0915”(physical association)	0.000
SPOP	PIP5K1B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (11): PIP5K1B (Affinity Capture-MS), SMURF1 (Affinity Capture-Western), PIP5K1B (Affinity Capture-MS), PIP5K1B (Affinity Capture-Western), PIP5K1B (Affinity Capture-MS), PIP5K1B (Affinity Capture-RNA), PIP5K1B (Affinity Capture-MS), MAPRE2 (Affinity Capture-MS), APAF1 (Affinity Capture-MS), PIP5K1B (Two-hybrid), PIP5K1B (Affinity Capture-RNA)

ESM2 similar proteins: A0A096MJN4, A2A3N6, A3KMI0, A6H8H2, B7ZC32, D3ZSI8, F1M4A4, F4IJV4, O14986, O43236, O48709, O73630, O80452, P08487, P10686, P19174, P19838, P23678, P25799, P33173, P41230, P70181, P70182, Q04861, Q12756, Q17BU3, Q3B8D5, Q5CZZ9, Q5VZ89, Q5XUN4, Q5ZJ58, Q62077, Q63369, Q6F3J0, Q6P3S1, Q6P5D3, Q7PHR1, Q7YTB0, Q7Z401, Q80UP5

Diamond homologs: A2A3N6, D3ZSI8, O13853, O14986, O17453, O35226, O48709, O60331, O61742, O70161, O82143, O88370, O88377, O94444, P38886, P38994, P55034, P55035, P55036, P70181, P70182, P78356, Q0P5F7, Q553E0, Q55GN6, Q56YP2, Q58DA0, Q5CZZ9, Q5F356, Q5I6B8, Q5PQ01, Q5R488, Q5ZJ58, Q6EX42, Q6GL14, Q6IQE1, Q80XI4, Q8I239, Q8L796, Q8L850

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRKCA	down-regulates	PIP5K1B	phosphorylation
SYK	“down-regulates activity”	PIP5K1B	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	44
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4082114	NM_003558.4(PIP5K1B):c.663_664del (p.Asn222fs)	Pathogenic
4082116	NM_003558.4(PIP5K1B):c.346G>A (p.Glu116Lys)	Pathogenic

SpliceAI

3733 predictions. Top by Δscore:

Variant	Effect	Δscore
9:68822612:TA:T	acceptor_loss	1.0000
9:68822613:A:AG	acceptor_gain	1.0000
9:68822613:AG:A	acceptor_loss	1.0000
9:68822614:G:GG	acceptor_gain	1.0000
9:68822614:GAT:G	acceptor_gain	1.0000
9:68822683:GGT:G	donor_loss	1.0000
9:68822684:G:GC	donor_loss	1.0000
9:68822685:T:A	donor_loss	1.0000
9:68863835:A:AG	acceptor_gain	1.0000
9:68863835:A:C	acceptor_loss	1.0000
9:68863835:AGACT:A	acceptor_gain	1.0000
9:68863836:G:GC	acceptor_loss	1.0000
9:68863836:G:GG	acceptor_gain	1.0000
9:68863836:GA:G	acceptor_gain	1.0000
9:68863836:GAC:G	acceptor_gain	1.0000
9:68863836:GACT:G	acceptor_gain	1.0000
9:68863836:GACTG:G	acceptor_gain	1.0000
9:68863966:AGGT:A	donor_loss	1.0000
9:68863967:GGTAA:G	donor_loss	1.0000
9:68863968:GTAAG:G	donor_loss	1.0000
9:68863969:T:G	donor_loss	1.0000
9:68876661:A:AG	acceptor_gain	1.0000
9:68876662:A:G	acceptor_gain	1.0000
9:68876664:ATTTT:A	acceptor_gain	1.0000
9:68888979:A:AG	acceptor_gain	1.0000
9:68888980:G:GG	acceptor_gain	1.0000
9:68888980:GT:G	acceptor_gain	1.0000
9:68888980:GTA:G	acceptor_gain	1.0000
9:68888980:GTAT:G	acceptor_gain	1.0000
9:68888980:GTATT:G	acceptor_gain	1.0000

AlphaMissense

3545 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:68863871:T:C	L35P	1.000
9:68863873:G:A	G36R	1.000
9:68863873:G:C	G36R	1.000
9:68863874:G:A	G36E	1.000
9:68863918:G:C	D51H	1.000
9:68863922:T:A	V52D	1.000
9:68863925:T:C	L53P	1.000
9:68863933:G:C	D56H	1.000
9:68863934:A:C	D56A	1.000
9:68863934:A:G	D56G	1.000
9:68863934:A:T	D56V	1.000
9:68863936:T:C	F57L	1.000
9:68863938:T:A	F57L	1.000
9:68863938:T:G	F57L	1.000
9:68876681:G:A	G69R	1.000
9:68876681:G:C	G69R	1.000
9:68876681:G:T	G69W	1.000
9:68876682:G:A	G69E	1.000
9:68876736:C:A	A87D	1.000
9:68876761:A:C	R95S	1.000
9:68876761:A:T	R95S	1.000
9:68876768:T:C	F98L	1.000
9:68876770:T:A	F98L	1.000
9:68876770:T:G	F98L	1.000
9:68889051:C:T	T130I	1.000
9:68889066:T:C	F135S	1.000
9:68889074:A:G	K138E	1.000
9:68889075:A:T	K138I	1.000
9:68889076:A:C	K138N	1.000
9:68889076:A:T	K138N	1.000

dbSNP variants (sampled 300 via entrez): RS1000002117 (9:68928835 A>G), RS1000002476 (9:68747402 C>T), RS1000004611 (9:69009154 G>A,C), RS1000018184 (9:68794687 G>T), RS1000026704 (9:68840954 C>T), RS1000033901 (9:68807114 C>T), RS1000038619 (9:68892133 C>G,T), RS1000054741 (9:68747098 T>C), RS1000061923 (9:68795153 G>A), RS1000076972 (9:68886174 G>A), RS1000085579 (9:68931137 C>T), RS1000089642 (9:68793038 A>T), RS1000095074 (9:68979491 G>A), RS1000114795 (9:68878432 A>G), RS1000143136 (9:68846729 C>G,T)

Disease associations

OMIM: gene MIM:602745 | disease phenotypes: MIM:143890

GenCC curated gene-disease

Mondo (1): familial hypercholesterolemia (MONDO:0005439)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000649_28	Chronic kidney disease	8.000000e-14
GCST003372_22	Glomerular filtration rate (creatinine)	4.000000e-15
GCST003401_25	Glomerular filtration rate in non diabetics (creatinine)	7.000000e-15
GCST003542_111	Night sleep phenotypes	1.000000e-06
GCST003790_18	Glomerular filtration rate	3.000000e-11
GCST004029_13	Angiotensin-converting enzyme inhibitor intolerance	6.000000e-06
GCST004292_24	Glomerular filtration rate (creatinine)	4.000000e-18
GCST004580_2	Body mass index (recreational physical activity interaction)	9.000000e-07
GCST007267_185	Systolic blood pressure	3.000000e-09
GCST007344_133	Estimated glomerular filtration rate	1.000000e-23
GCST007344_22	Estimated glomerular filtration rate	5.000000e-10
GCST007344_27	Estimated glomerular filtration rate	1.000000e-26
GCST007877_12	Creatinine levels	5.000000e-13
GCST008058_206	Estimated glomerular filtration rate	2.000000e-62
GCST008059_116	Estimated glomerular filtration rate	3.000000e-56
GCST008064_10	Chronic kidney disease	5.000000e-08
GCST008745_71	Estimated glomerular filtration rate in non-diabetics	2.000000e-13
GCST008746_22	Estimated glomerular filtration rate in diabetes	6.000000e-09
GCST008747_104	Estimated glomerular filtration rate	1.000000e-40
GCST008747_147	Estimated glomerular filtration rate	5.000000e-33
GCST90002401_480	Platelet distribution width	2.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0005325	response to angiotensin-converting enzyme inhibitor
EFO:0004340	body mass index
EFO:0008002	physical activity measurement
EFO:0006335	systolic blood pressure
EFO:0007984	platelet component distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4802064 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Phosphatidylinositol phosphate kinases

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.89	IC50	13	nM	CHEMBL5171272
7.46	IC50	35	nM	CHEMBL5191668
7.34	IC50	46	nM	CHEMBL5206569
6.00	IC50	1000	nM	CHEMBL203535
5.72	IC50	1900	nM	CHEMBL6162267

PubChem BioAssay actives

4 with measured affinity, of 4 total; 4 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-[4-[3-anilino-5-(methylcarbamoyl)phenyl]-2-pyridinyl]oxane-4-carboxamide	1888784: Inhibition of PIP5Kbeta (unknown origin)	ic50	0.0130	uM
N-[4-(3-acetamido-5-anilinophenyl)-2-pyridinyl]oxane-4-carboxamide	1888784: Inhibition of PIP5Kbeta (unknown origin)	ic50	0.0350	uM
3-anilino-5-[2-(cyclopropanecarbonylamino)-4-pyridinyl]-N-(1,3-dioxolan-2-ylmethyl)-N-methylbenzamide	1888784: Inhibition of PIP5Kbeta (unknown origin)	ic50	0.0460	uM
N-[4-(2-anilino-4-pyridinyl)-2-pyridinyl]oxolane-3-carboxamide	1888784: Inhibition of PIP5Kbeta (unknown origin)	ic50	1.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases methylation, affects methylation, decreases expression	5
trichostatin A	affects cotreatment, decreases expression	3
Valproic Acid	affects cotreatment, decreases expression	3
Aflatoxin B1	increases methylation, decreases expression, decreases methylation	3
Estradiol	increases expression, decreases expression, affects cotreatment	2
Cyclosporine	decreases expression, increases expression	2
dicrotophos	decreases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
lead acetate	decreases expression, affects cotreatment	1
arsenite	affects expression	1
sulforaphane	decreases expression	1
chromous chloride	affects cotreatment, decreases expression	1
sodium arsenite	decreases expression, affects cotreatment	1
chromic oxide	decreases expression, affects cotreatment	1
triadimefon	increases expression	1
di-n-butylphosphoric acid	affects 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, decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	increases methylation, affects cotreatment	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Leflunomide	increases expression	1
Acetaminophen	decreases expression	1
Azathioprine	decreases expression	1
Doxorubicin	decreases expression	1
Etoposide	affects response to substance	1
Iron	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4887309	Binding	PIP5K1B Invitrogen Lab (UK) kinase screen (BI)	Data for DCP probe BI 605906

Cellosaurus cell lines

2 cell lines: 1 transformed cell line, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9NJ	Ubigene HEK293 PIP5K1B KO	Transformed cell line	Female
CVCL_E0KW	Ubigene HeLa PIP5K1B KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00655265	PHASE4	COMPLETED	A Study of the Safety and Efficacy of Patients With Familial Hypercholesterolaemia Taking Colesevelam as add-on Therapy to Their Existing Medication
NCT00916643	PHASE4	COMPLETED	Low-Density Lipoprotein (LDL) Apheresis Using H.E.L.P. Therapy
NCT03331666	PHASE4	TERMINATED	Impact of LDL-cholesterol Lowering on Platelet Activation
NCT05465278	PHASE4	COMPLETED	Alirocumab and Plaque Burden In Familial Hypercholesterolaemia
NCT00355615	PHASE3	COMPLETED	PLUTO: Pediatric Lipid-redUction Trial of rOsuvastatin
NCT00552097	PHASE3	COMPLETED	Effect of Ezetimibe Plus Simvastatin Versus Simvastatin Alone on Atherosclerosis in the Carotid Artery (ENHANCE)(P02578)
NCT00607373	PHASE3	COMPLETED	Study to Assess the Safety and Efficacy of ISIS 301012 (Mipomersen) in Homozygous Familial Hypercholesterolemia
NCT00694109	PHASE3	COMPLETED	An Open-label Extension Study to Assess the Long-term Safety and Efficacy of ISIS 301012 (Mipomersen) in Patients With Familial Hypercholesterolemia or Severe-Hypercholesterolemia
NCT00827606	PHASE3	COMPLETED	Atorvastatin Three Year Pediatric Study
NCT00943306	PHASE3	COMPLETED	Long Term, Follow-on Study of Lomitapide in Patients With Homozygous Familial Hypercholesterolemia
NCT01524289	PHASE3	COMPLETED	Study to Assess the Tolerability and Efficacy of Anacetrapib (MK-0859) Co-Administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020)
NCT01813006	PHASE3	COMPLETED	Effect of Omega-3 Fatty Acid on Endothelial Function
NCT01841684	PHASE3	TERMINATED	Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042)
NCT02624869	PHASE3	COMPLETED	Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Children With Inherited Elevated Low-density Lipoprotein Cholesterol (Familial Hypercholesterolemia)
NCT02748057	PHASE3	COMPLETED	A Clinical Trial to Assess the Long Term Safety and Tolerability of MK-0653H in Japanese Participants With Hypercholesterolemia (MK-0653H-833)
NCT03884452	PHASE3	COMPLETED	Ezetimibe (SCH 58235) Taken With Either Atorvastatin or Simvastatin in Participants With Familial Hypercholesterolemia (MK-0653-018)
NCT04798430	PHASE3	ENROLLING_BY_INVITATION	Long-term Efficacy and Safety of OLE LIB003 in HoFH, HeFH, and High-risk CVD Patients Requiring Further LDL-C Reduction
NCT05142722	PHASE3	COMPLETED	Randomized Study to Evaluate the Effect of Obicetrapib on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT05238519	PHASE3	ACTIVE_NOT_RECRUITING	Improved Diagnosis of Familial Hypercholesterolemia Across the Northland (ID-FH)
NCT05425745	PHASE3	COMPLETED	Evaluate the Effect of Obicetrapib in Patients With HeFH on Top of Maximum Tolerated Lipid-Modifying Therapies.
NCT05952856	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-013) CORALreef Lipids
NCT05952869	PHASE3	COMPLETED	A Study of Enlicitide Decanoate (MK-0616 Oral PCSK9 Inhibitor) in Adults With Heterozygous Familial Hypercholesterolemia (MK-0616-017/CORALreef HeFH)
NCT06005597	PHASE3	COMPLETED	Study of Obicetrapib & Ezetimibe Fixed Dose Combination on Top of Maximum Tolerated Lipid-Modifying Therapies
NCT00079846	PHASE2	TERMINATED	Implitapide in Patients With Homozygous Familial Hypercholesterolemia (HoFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00079859	PHASE2	TERMINATED	Implitapide in Patients With Heterozygous Familial Hypercholesterolemia (HeFH) on Maximal Concurrent Lipid-Lowering Therapy
NCT00477594	PHASE2	COMPLETED	Open Label Extension of ISIS 301012 (Mipomersen) to Treat Familial Hypercholesterolemia
NCT00751608	PHASE2	WITHDRAWN	Effect of APL180 on Endothelial Function in Familial Hypercholesterolemia Patients
NCT02597127	PHASE2	COMPLETED	Trial to Evaluate the Effect of ALN-PCSSC Treatment on Low Density Lipoprotein Cholesterol (LDL-C)
NCT03060577	PHASE2	COMPLETED	An Extension Trial of Inclisiran in Participants With Cardiovascular Disease and High Cholesterol
NCT04455581	PHASE2	UNKNOWN	A Study to Determine the Safety, Tolerability, and Efficacy of SHR-1209 in Patients With Familial Hypercholesterolemia
NCT04941599	PHASE2	RECRUITING	2-Hydroxybenzylamine (2-HOBA) to Reduce HDL Modification and Improve HDL Function in Familial Hypercholesterolemia (FH)
NCT05261126	PHASE2	COMPLETED	A Study of the Efficacy and Safety of Enclitide Chloride (MK-0616 Oral PCSK9 Inhibitor) in Adults With Hypercholesterolemia (MK-0616-008)
NCT00004809	PHASE1	COMPLETED	Phase I Study of Ex Vivo Liver-Directed Gene Therapy for Familial Hypercholesterolemia
NCT02709850	PHASE1	COMPLETED	Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of IONIS ANGPTL3-LRx in Healthy Volunteers With Elevated Triglycerides and Participants With Familial Hypercholesterolemia
NCT03747224	PHASE1	COMPLETED	Study of ARO-ANG3 in Healthy Volunteers and in Dyslipidemic Patients
NCT05043181	PHASE1	NOT_YET_RECRUITING	Exosome-based Nanoplatform for Ldlr mRNA Delivery in FH
NCT05851066	PHASE1	COMPLETED	A VSA003 Phase 1 Study in Chinese Adult Healthy Volunteers
NCT02048410	PHASE1/PHASE2	COMPLETED	Efficacy of a New Symbiotic Formulation in Children With Familial Hypercholesterolemia
NCT02100839	PHASE1/PHASE2	COMPLETED	Safety Study of AEM-28 to Treat Refractory Hypercholesterolemia
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results