PIP5KL1

Summary

PIP5KL1 (phosphatidylinositol-4-phosphate 5-kinase like 1, HGNC:28711) is a protein-coding gene on chromosome 9q34.11, encoding Phosphatidylinositol 4-phosphate 5-kinase-like protein 1 (Q5T9C9). May act as a scaffold to localize and regulate type I PI(4)P 5-kinases to specific compartments within the cell, where they generate PI(4,5)P2 for actin nucleation, signaling and scaffold protein recruitment and conversion to PI(3,4,5)P3.

PIP5KL1 is a phosphoinositide kinase-like protein that lacks intrinsic lipid kinase activity but associates with type I PIPKs (see PIP5K1A; MIM 603275) and may play a role in localization of PIPK activity (Chang et al., 2004 [PubMed 14701839]).

Source: NCBI Gene 138429 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 64 total
• MANE Select transcript: NM_001135219

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28711
Approved symbol	PIP5KL1
Name	phosphatidylinositol-4-phosphate 5-kinase like 1
Location	9q34.11
Locus type	gene with protein product
Status	Approved
Aliases	bA203J24.5, MGC46424, PIPKH
Ensembl gene	ENSG00000167103
Ensembl biotype	protein_coding
OMIM	612865
Entrez	138429

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000300432, ENST00000388747, ENST00000464108, ENST00000464759, ENST00000476624, ENST00000477191, ENST00000485562, ENST00000490773, ENST00000492296, ENST00000495448, ENST00000497234, ENST00000498783

RefSeq mRNA: 2 — MANE Select: NM_001135219 NM_001135219, NM_173492

CCDS: CCDS48030, CCDS6885

Canonical transcript exons

ENST00000388747 — 10 exons

Exon	Start	End
ENSE00001843550	127920881	127922114
ENSE00002288474	127930723	127930777
ENSE00003520527	127927153	127927208
ENSE00003529788	127929688	127929885
ENSE00003546523	127928065	127928219
ENSE00003568140	127925867	127925979
ENSE00003644117	127928433	127928483
ENSE00003645938	127925107	127925260
ENSE00003670317	127927297	127927331
ENSE00003692337	127927648	127927772

Expression profiles

Bgee: expression breadth ubiquitous, 158 present calls, max score 83.72.

FANTOM5 (CAGE): breadth broad, TPM avg 0.5574 / max 136.5879, expressed in 232 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
102621	0.1590	55
102623	0.1543	72
102620	0.1280	39
102618	0.0815	47
102622	0.0252	8
102619	0.0093	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
upper arm skin	UBERON:0004263	83.72	gold quality
lower esophagus mucosa	UBERON:0035834	81.46	gold quality
bone marrow cell	CL:0002092	77.69	gold quality
left ventricle myocardium	UBERON:0006566	76.69	gold quality
cardiac muscle of right atrium	UBERON:0003379	76.68	gold quality
parotid gland	UBERON:0001831	75.28	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	73.88	gold quality
skin of abdomen	UBERON:0001416	73.80	gold quality
stromal cell of endometrium	CL:0002255	73.24	gold quality
esophagus mucosa	UBERON:0002469	72.97	gold quality
cortical plate	UBERON:0005343	72.69	gold quality
prefrontal cortex	UBERON:0000451	72.43	gold quality
skin of leg	UBERON:0001511	72.32	gold quality
ventricular zone	UBERON:0003053	72.26	gold quality
pituitary gland	UBERON:0000007	71.70	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	71.54	gold quality
adenohypophysis	UBERON:0002196	71.09	gold quality
epithelial cell of pancreas	CL:0000083	70.81	gold quality
zone of skin	UBERON:0000014	70.73	gold quality
ectocervix	UBERON:0012249	70.58	gold quality
saliva-secreting gland	UBERON:0001044	70.36	gold quality
minor salivary gland	UBERON:0001830	70.06	gold quality
mucosa of stomach	UBERON:0001199	69.85	gold quality
vagina	UBERON:0000996	69.62	gold quality
right frontal lobe	UBERON:0002810	69.61	gold quality
nasal cavity epithelium	UBERON:0005384	69.52	gold quality
esophagus	UBERON:0001043	69.09	gold quality
right hemisphere of cerebellum	UBERON:0014890	68.99	gold quality
anterior cingulate cortex	UBERON:0009835	68.91	gold quality
kidney epithelium	UBERON:0004819	68.63	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-36552	no	19.10
E-ANND-3	no	2.47

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

19 targeting PIP5KL1, 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-3605-5P	99.96	67.12	932
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-4527	99.66	67.43	714
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-6503-5P	99.62	66.96	597
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-1252-3P	99.55	67.71	2862
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-4311	99.31	70.47	3041
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-556-5P	97.75	66.17	473
HSA-MIR-8055	97.62	66.09	1023
HSA-MIR-610	96.84	67.98	905
HSA-MIR-3679-5P	94.75	66.46	862
HSA-MIR-1185-5P	94.47	65.95	725

Literature-anchored findings (GeneRIF, showing 3)

• PIPKH acts as a scaffold to localize and regulate type I PI(4)P 5-kinases and the synthesis of PI(3,4,5)P(3) (PMID:14701839)
• These studies indicate a functional negative correlation between elevated levels of PIP5KL1 and the development of human gastric cancer. (PMID:19680787)
• Enforced expression of phosphatidylinositol 4-phosphate 5-kinase homolog alters PtdIns(4,5)P2 distribution and the localization of small G-proteins. (PMID:31616009)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	pip5kl1	ENSDARG00000060946
mus_musculus	Pip5kl1	ENSMUSG00000046854
rattus_norvegicus	Pip5kl1	ENSRNOG00000048676

Paralogs (6): PIP5K1B (ENSG00000107242), PIP5K1A (ENSG00000143398), PIP4K2A (ENSG00000150867), PIP4K2C (ENSG00000166908), PIP5K1C (ENSG00000186111), PIP4K2B (ENSG00000276293)

Protein

Protein identifiers

Phosphatidylinositol 4-phosphate 5-kinase-like protein 1 — Q5T9C9 (reviewed: Q5T9C9)

All UniProt accessions (1): Q5T9C9

UniProt curated annotations — full annotation on UniProt →

Function. May act as a scaffold to localize and regulate type I PI(4)P 5-kinases to specific compartments within the cell, where they generate PI(4,5)P2 for actin nucleation, signaling and scaffold protein recruitment and conversion to PI(3,4,5)P3.

Subunit / interactions. Heterodimerizes with other type I phosphatidylinositol 4-phosphate 5-kinase.

Subcellular location. Cytoplasm. Membrane.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5T9C9-1	1	yes
Q5T9C9-2	2

RefSeq proteins (2): NP_001128691, NP_775763 (=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

Catalyzed reactions (Rhea), 1 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)

UniProt features (3 total): chain 1, domain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5T9C9-F1	85.21	0.66

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, GOBP_PHOSPHOLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_PHOSPHATIDYLINOSITOL_3_KINASE_PROTEIN_KINASE_B_SIGNAL_TRANSDUCTION, GOBP_GLYCEROLIPID_BIOSYNTHETIC_PROCESS, GOBP_GLYCEROPHOSPHOLIPID_METABOLIC_PROCESS, GOBP_LIPID_METABOLIC_PROCESS, GOBP_LIPID_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_MITOCHONDRIAL_MEMBRANE_POTENTIAL

GO Biological Process (8): negative regulation of mitochondrial membrane potential (GO:0010917), negative regulation of cell migration (GO:0030336), positive regulation of apoptotic process (GO:0043065), phosphatidylinositol phosphate biosynthetic process (GO:0046854), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), lipid metabolic process (GO:0006629), regulation of signal transduction (GO:0009966), phosphatidylinositol metabolic process (GO:0046488)

GO Molecular Function (6): ATP binding (GO:0005524), 1-phosphatidylinositol-4-phosphate 5-kinase activity (GO:0016308), nucleotide binding (GO:0000166), kinase activity (GO:0016301), transferase activity (GO:0016740), phosphatidylinositol kinase activity (GO:0052742)

GO Cellular Component (5): cytosol (GO:0005829), plasma membrane (GO:0005886), cell projection (GO:0042995), cytoplasm (GO:0005737), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of membrane potential	1
regulation of mitochondrial membrane potential	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
glycerophospholipid biosynthetic process	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
negative 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
phosphatidylinositol kinase activity	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
lipid kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
cytoplasm	1
membrane	1
cell periphery	1
intracellular anatomical structure	1

Protein interactions and networks

STRING

684 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIP5KL1	ANKRD13B	Q86YJ7	512
PIP5KL1	PIP5K1A	Q99755	499
PIP5KL1	TMEM25	Q86YD3	491
PIP5KL1	TMEM91	Q6ZNR0	451
PIP5KL1	USP17L7	P0C7H9	448
PIP5KL1	TMEM117	Q9H0C3	441
PIP5KL1	MBOAT1	Q6ZNC8	405
PIP5KL1	GRIFIN	A4D1Z8	403
PIP5KL1	EEIG1	Q5T9C2	400
PIP5KL1	DPM2	O94777	398
PIP5KL1	PIK3CD	O00329	394
PIP5KL1	PLPPR3	Q6T4P5	364
PIP5KL1	GPR160	Q9UJ42	355
PIP5KL1	USP53	Q70EK8	342
PIP5KL1	EML1	O00423	338

IntAct

3 interactions, top by confidence:

A	B	Type	Score
PIP5KL1	HSPA9	psi-mi:“MI:0915”(physical association)	0.400
PIP5KL1	ABCF3	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (5): PIP5K1B (Affinity Capture-Western), PIP5K1C (Affinity Capture-Western), PIP5K1A (Affinity Capture-Western), PIP5KL1 (Proximity Label-MS), ABCF3 (Affinity Capture-MS)

ESM2 similar proteins: A4FV98, A5PK51, A6NDG6, E1BE10, O00587, O35595, O95294, P60487, Q12788, Q17QS4, Q1JPJ0, Q2T9S4, Q2TBI8, Q32NY4, Q3T063, Q3ZBF9, Q501J2, Q5E9V4, Q5F4B1, Q5IS64, Q5SUV1, Q5T9C9, Q6AYG0, Q6AYR8, Q6XQN1, Q6XQN6, Q6ZMM2, Q80US4, Q8BNV1, Q8BZG5, Q8CC86, Q8IZ69, Q8N9H8, Q8NE01, Q8R2H9, Q8TCT1, Q8VCA8, Q8VD52, Q969S8, Q96AZ1

Diamond homologs: B0G126, Q17QS4, Q5T9C9, Q6U7H8, Q9LMN1, Q9SSJ8, Q9LUM0, O48709, O96838, P38994, Q56YP2, Q6EX42, Q8L796, Q8L850, Q8RY89, Q9M149, Q9M1K2, Q9SFB8, Q9SLG9, Q9SUI2, O13853, O88377, Q0WUR5, Q55GN6, Q80XI4, Q9XID0

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1799 predictions. Top by Δscore:

Variant	Effect	Δscore
9:127925101:GCTCA:G	donor_loss	1.0000
9:127925102:CTCAC:C	donor_loss	1.0000
9:127925103:TCACC:T	donor_loss	1.0000
9:127925104:CACCT:C	donor_loss	1.0000
9:127925105:ACCTG:A	donor_loss	1.0000
9:127925106:C:CA	donor_loss	1.0000
9:127925981:T:A	acceptor_loss	1.0000
9:127927148:CTCA:C	donor_loss	1.0000
9:127927150:CA:C	donor_loss	1.0000
9:127927151:A:AC	donor_gain	1.0000
9:127927152:C:CC	donor_gain	1.0000
9:127927152:CCT:C	donor_gain	1.0000
9:127927206:CGT:C	acceptor_gain	1.0000
9:127927329:CTC:C	acceptor_gain	1.0000
9:127927644:GTACC:G	donor_loss	1.0000
9:127927646:A:AC	donor_gain	1.0000
9:127927646:A:T	donor_loss	1.0000
9:127927646:AC:A	donor_gain	1.0000
9:127927647:C:CA	donor_loss	1.0000
9:127927647:C:CC	donor_gain	1.0000
9:127927647:CC:C	donor_gain	1.0000
9:127927700:G:C	donor_gain	1.0000
9:127927768:CGTGG:C	acceptor_gain	1.0000
9:127927769:GTGG:G	acceptor_gain	1.0000
9:127927770:TGG:T	acceptor_gain	1.0000
9:127927770:TGGC:T	acceptor_loss	1.0000
9:127927771:GG:G	acceptor_gain	1.0000
9:127927772:GCT:G	acceptor_loss	1.0000
9:127927773:C:CC	acceptor_gain	1.0000
9:127927773:C:CG	acceptor_loss	1.0000

AlphaMissense

2533 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:127925968:T:A	K221I	0.997
9:127925967:T:A	K221N	0.994
9:127925967:T:G	K221N	0.994
9:127927748:C:A	K153N	0.985
9:127927748:C:G	K153N	0.985
9:127925892:G:C	N246K	0.984
9:127925892:G:T	N246K	0.984
9:127925901:C:A	K243N	0.982
9:127925901:C:G	K243N	0.982
9:127925181:G:C	S281R	0.980
9:127925181:G:T	S281R	0.980
9:127925183:T:G	S281R	0.980
9:127925899:T:G	D244A	0.976
9:127925969:T:C	K221E	0.976
9:127925973:G:C	D219E	0.976
9:127925973:G:T	D219E	0.976
9:127925900:C:G	D244H	0.974
9:127928214:G:C	F95L	0.974
9:127928214:G:T	F95L	0.974
9:127928216:A:G	F95L	0.974
9:127925974:T:C	D219G	0.973
9:127925974:T:G	D219A	0.972
9:127925978:A:C	Y218D	0.972
9:127928174:G:T	R109S	0.972
9:127928103:G:C	F132L	0.971
9:127928103:G:T	F132L	0.971
9:127928105:A:G	F132L	0.971
9:127927185:G:C	S206R	0.970
9:127927185:G:T	S206R	0.970
9:127927187:T:G	S206R	0.970

dbSNP variants (sampled 300 via entrez): RS1000048528 (9:127923478 C>G), RS1000268301 (9:127923661 CCAA>C), RS1000997704 (9:127930149 G>A), RS1001032846 (9:127923707 G>A,C), RS1001035524 (9:127921812 A>T), RS1001124699 (9:127927703 G>A,C), RS1001836891 (9:127932609 C>G), RS1001899461 (9:127932190 A>C), RS1002057554 (9:127920554 C>T), RS1002381954 (9:127929379 C>G), RS1002432772 (9:127929753 T>A), RS1003116633 (9:127926667 C>T), RS1003249198 (9:127930941 G>A,C), RS1003362980 (9:127921243 G>A), RS1003387196 (9:127927932 A>G)

Disease associations

OMIM: gene MIM:612865 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST005951_65	Body mass index	5.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	decreases expression	1
bisphenol A	decreases expression	1
sodium arsenite	increases abundance, affects cotreatment, decreases expression	1
perfluorooctanoic acid	increases expression	1
2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline	decreases expression	1
clothianidin	decreases expression	1
bisphenol S	increases methylation	1
jinfukang	affects cotreatment, increases expression	1
Microplastics	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Cisplatin	affects cotreatment, increases expression	1
Polyethylene Terephthalates	decreases expression, increases abundance	1
Rotenone	increases expression	1
Smoke	decreases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

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