PIP4P2

Summary

PIP4P2 (phosphatidylinositol-4,5-bisphosphate 4-phosphatase 2, HGNC:25452) is a protein-coding gene on chromosome 8q21.3, encoding Type 2 phosphatidylinositol 4,5-bisphosphate 4-phosphatase (Q8N4L2). Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P).

TMEM55A catalyzes the degradation of phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P2) by removing the 4-phosphate (Ungewickell et al., 2005 [PubMed 16365287]).

Source: NCBI Gene 55529 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 47 total
• MANE Select transcript: NM_018710

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25452
Approved symbol	PIP4P2
Name	phosphatidylinositol-4,5-bisphosphate 4-phosphatase 2
Location	8q21.3
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp762O076
Ensembl gene	ENSG00000155099
Ensembl biotype	protein_coding
OMIM	609864
Entrez	55529

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 8 protein_coding, 3 nonsense_mediated_decay

ENST00000285419, ENST00000518359, ENST00000518869, ENST00000520014, ENST00000520709, ENST00000630164, ENST00000886895, ENST00000886896, ENST00000886897, ENST00000920105, ENST00000920106

RefSeq mRNA: 1 — MANE Select: NM_018710 NM_018710

CCDS: CCDS6252

Canonical transcript exons

ENST00000285419 — 7 exons

Exon	Start	End
ENSE00001019185	90993802	90995820
ENSE00001227162	91040644	91040859
ENSE00003469941	91021256	91021404
ENSE00003533045	91020157	91020263
ENSE00003605519	91018390	91018513
ENSE00003650475	90996654	90996744
ENSE00003663430	91008743	91008795

Expression profiles

Bgee: expression breadth ubiquitous, 247 present calls, max score 96.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 43.8022 / max 866.7855, expressed in 1817 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
93907	42.2004	1817
93909	0.5321	202
93908	0.4286	212
93906	0.4039	189
93905	0.2371	121

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pigmented layer of retina	UBERON:0001782	96.42	gold quality
retina	UBERON:0000966	96.40	gold quality
substantia nigra pars compacta	UBERON:0001965	92.76	gold quality
pons	UBERON:0000988	92.73	gold quality
monocyte	CL:0000576	92.54	gold quality
leukocyte	CL:0000738	92.13	gold quality
prefrontal cortex	UBERON:0000451	91.60	gold quality
substantia nigra pars reticulata	UBERON:0001966	91.58	gold quality
bone marrow	UBERON:0002371	90.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	90.92	gold quality
bone marrow cell	CL:0002092	90.53	gold quality
blood	UBERON:0000178	90.51	gold quality
superior vestibular nucleus	UBERON:0007227	89.71	gold quality
dorsal plus ventral thalamus	UBERON:0001897	89.23	gold quality
cortical plate	UBERON:0005343	89.16	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	89.06	gold quality
hypothalamus	UBERON:0001898	89.05	gold quality
substantia nigra	UBERON:0002038	88.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	88.94	gold quality
midbrain	UBERON:0001891	88.91	gold quality
popliteal artery	UBERON:0002250	88.88	gold quality
tibial artery	UBERON:0007610	88.86	gold quality
dorsal root ganglion	UBERON:0000044	88.73	gold quality
spinal cord	UBERON:0002240	88.69	gold quality
cerebellar vermis	UBERON:0004720	88.66	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	88.66	gold quality
subthalamic nucleus	UBERON:0001906	88.48	gold quality
anterior cingulate cortex	UBERON:0009835	88.48	gold quality
artery	UBERON:0001637	88.46	gold quality
ventral tegmental area	UBERON:0002691	88.31	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	39.06
E-ANND-3	yes	14.30
E-MTAB-7008	no	171.13

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

162 targeting PIP4P2, 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-5692A	100.00	74.40	6850
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548P	99.98	72.25	3784
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3065-5P	99.97	71.56	3281

Literature-anchored findings (GeneRIF, showing 2)

• identification and characterization of two previously undescribed human enzymes, PtdIns-4,5-P(2) 4-phosphatase type I and type II (PMID:16365287)
• CRISPRa Analysis of Phosphoinositide Phosphatases Shows That TMEM55A Is a Positive Regulator of Autophagy. (PMID:38880622)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	pip4p2	ENSDARG00000056034
mus_musculus	Pip4p2	ENSMUSG00000028221
rattus_norvegicus	Pip4p2	ENSRNOG00000006697
drosophila_melanogaster	CG6707	FBGN0036058
caenorhabditis_elegans		WBGENE00018697
caenorhabditis_elegans		WBGENE00022167

Paralogs (1): PIP4P1 (ENSG00000165782)

Protein

Protein identifiers

Type 2 phosphatidylinositol 4,5-bisphosphate 4-phosphatase — Q8N4L2 (reviewed: Q8N4L2)

Alternative names: PtdIns-4,5-P2 4-Ptase II, Transmembrane protein 55A

All UniProt accessions (5): Q8N4L2, E5RFT4, E5RIP9, E5RIY0, E5RJC2

UniProt curated annotations — full annotation on UniProt →

Function. Catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P). Does not hydrolyze phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3,4-bisphosphate, inositol 3,5-bisphosphate, inositol 3,4-bisphosphate, phosphatidylinositol 5-monophosphate, phosphatidylinositol 4-monophosphate and phosphatidylinositol 3-monophosphate. Negatively regulates the phagocytosis of large particles by reducing phagosomal phosphatidylinositol 4,5-bisphosphate accumulation during cup formation.

Subcellular location. Late endosome membrane. Lysosome membrane. Cytoplasmic vesicle. Phagosome membrane. Cell membrane.

Tissue specificity. Ubiquitous.

RefSeq proteins (1): NP_061180* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019178	PtdIns-P2-Ptase	Family

Pfam: PF09788

Enzyme classification (BRENDA):

• EC 3.1.3.78 — phosphatidylinositol-4,5-bisphosphate 4-phosphatase (BRENDA: 4 organisms, 13 substrates, 2 inhibitors, 0 Km, 0 kcat entries)

Catalyzed reactions (Rhea), 1 shown:

• a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-4,5-bisphosphate) + H2O = a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol-5-phosphate) + phosphate (RHEA:25674)

UniProt features (10 total): transmembrane region 2, compositionally biased region 2, modified residue 2, chain 1, region of interest 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N4L2-F1	72.89	0.12

Functional residue map

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

Catalytic / active sites (1): 107

Post-translational modifications (2): 22, 33

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 228 (showing top): GOBP_LIPID_MODIFICATION, AAGCAAT_MIR137, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHATIDYLINOSITOL_METABOLIC_PROCESS, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOCC_VACUOLAR_MEMBRANE, TTTGTAG_MIR520D, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_REGULATION_OF_VESICLE_MEDIATED_TRANSPORT, GOBP_NEGATIVE_REGULATION_OF_CELLULAR_COMPONENT_ORGANIZATION, GOBP_GLYCEROLIPID_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_TRANSPORT

GO Biological Process (3): phosphatidylinositol dephosphorylation (GO:0046856), negative regulation of phagocytosis (GO:0050765), lipid metabolic process (GO:0006629)

GO Molecular Function (3): phosphatidylinositol-4,5-bisphosphate 4-phosphatase activity (GO:0034597), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (8): lysosomal membrane (GO:0005765), plasma membrane (GO:0005886), phagocytic vesicle membrane (GO:0030670), late endosome membrane (GO:0031902), lysosome (GO:0005764), endosome (GO:0005768), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
phosphatidylinositol metabolic process	1
phospholipid dephosphorylation	1
phagocytosis	1
negative regulation of endocytosis	1
regulation of phagocytosis	1
primary metabolic process	1
phosphatidylinositol phosphate 4-phosphatase activity	1
phosphatidylinositol-4,5-bisphosphate phosphatase activity	1
binding	1
catalytic activity	1
lysosome	1
lytic vacuole membrane	1
membrane	1
cell periphery	1
endocytic vesicle membrane	1
phagocytic vesicle	1
late endosome	1
endosome membrane	1
lytic vacuole	1
endomembrane system	1
cytoplasmic vesicle	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

446 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PIP4P2	SLC35E4	Q6ICL7	452
PIP4P2	ZNF358	Q9NW07	439
PIP4P2	PIP4K2A	P48426	436
PIP4P2	AKAP1	Q92667	435
PIP4P2	PLPPR4	Q7Z2D5	404
PIP4P2	TSEN54	Q7Z6J9	378
PIP4P2	PI4KA	P42356	375
PIP4P2	SLC66A2	Q8N2U9	361
PIP4P2	FAM43A	Q8N2R8	360
PIP4P2	PI4K2A	Q9BTU6	358
PIP4P2	TTC7B	Q86TV6	351
PIP4P2	MTMR4	Q9NYA4	341
PIP4P2	MREG	Q8N565	339
PIP4P2	INPP5E	Q9NRR6	337
PIP4P2	CREBL2	O60519	332
PIP4P2	TMEM117	Q9H0C3	332

IntAct

81 interactions, top by confidence:

A	B	Type	Score
DFFB	DFFA	psi-mi:“MI:0914”(association)	0.940
CDK5RAP3	UFL1	psi-mi:“MI:0914”(association)	0.870
IFT70B	IFT56	psi-mi:“MI:0914”(association)	0.790
TBC1D9	ABHD16A	psi-mi:“MI:0914”(association)	0.640
SLC39A5	FAM171A2	psi-mi:“MI:0914”(association)	0.640
NEDD4	PIP4P2	psi-mi:“MI:0407”(direct interaction)	0.590
PIP4P2	NEDD4	psi-mi:“MI:0914”(association)	0.590
TNF	PIP4P2	psi-mi:“MI:0915”(physical association)	0.560
ZFYVE27	PIP4P2	psi-mi:“MI:0915”(physical association)	0.560
SLC10A6	PIP4P2	psi-mi:“MI:0915”(physical association)	0.560
SLC39A5	TMEM223	psi-mi:“MI:0914”(association)	0.530
GDPD5	GOLIM4	psi-mi:“MI:0914”(association)	0.530
ARC	FER	psi-mi:“MI:0914”(association)	0.530
PINK1	CLUH	psi-mi:“MI:0914”(association)	0.530
SGSM1	CETN2	psi-mi:“MI:0914”(association)	0.530
PRKAG3	PFDN6	psi-mi:“MI:0914”(association)	0.530
F9	UBR5	psi-mi:“MI:0914”(association)	0.530
CCT8L2	ACSL4	psi-mi:“MI:0914”(association)	0.530
CDK5RAP3	PLD2	psi-mi:“MI:0914”(association)	0.530
GPRC5B	STXBP3	psi-mi:“MI:0914”(association)	0.530
ITCH	PIP4P2	psi-mi:“MI:0407”(direct interaction)	0.440
TSG101	PIP4P2	psi-mi:“MI:0407”(direct interaction)	0.440
gag	PIP4P2	psi-mi:“MI:0915”(physical association)	0.400
	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (61): TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Two-hybrid), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS), TMEM55A (Two-hybrid), ZFYVE27 (Two-hybrid), TNF (Two-hybrid), TMEM55A (Affinity Capture-MS), TMEM55A (Affinity Capture-MS)

ESM2 similar proteins: B4DJY2, D3Z1U7, D3ZEH5, D4A9I3, Q13507, Q15012, Q17QL9, Q3SZ48, Q4R4I5, Q4V888, Q5JRV8, Q5RAH0, Q5RCY9, Q5RET6, Q5U1W4, Q5U239, Q5ZMP3, Q60961, Q61143, Q69ZS6, Q6P501, Q6X893, Q7TMP6, Q86UP9, Q8BG21, Q8BHW5, Q8CIF6, Q8N4L2, Q8NA29, Q8NBJ9, Q8VHW4, Q8VHW8, Q8VII6, Q8WWI5, Q91XQ6, Q969E2, Q9BE63, Q9BX95, Q9CZX7, Q9DA37

Diamond homologs: Q32PR0, Q3SZ48, Q3TWL2, Q4R6W2, Q4V888, Q5EAU3, Q5PPM8, Q5XKA6, Q66I51, Q6DIE4, Q86T03, Q8N4L2, Q9CZX7

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1233 predictions. Top by Δscore:

Variant	Effect	Δscore
8:91008741:A:AC	donor_gain	1.0000
8:91008742:C:CC	donor_gain	1.0000
8:91008796:C:CC	acceptor_gain	1.0000
8:91018385:CTT:C	donor_loss	1.0000
8:91018386:TTA:T	donor_loss	1.0000
8:91018387:TACCA:T	donor_loss	1.0000
8:91018388:A:AC	donor_gain	1.0000
8:91018389:C:CC	donor_gain	1.0000
8:91018509:GTCTA:G	acceptor_gain	1.0000
8:91018510:TCTA:T	acceptor_loss	1.0000
8:91018511:CTA:C	acceptor_gain	1.0000
8:91018511:CTAC:C	acceptor_loss	1.0000
8:91018512:TA:T	acceptor_gain	1.0000
8:91018513:ACT:A	acceptor_loss	1.0000
8:91018514:C:CC	acceptor_gain	1.0000
8:91018514:CTGTG:C	acceptor_loss	1.0000
8:91018515:T:A	acceptor_loss	1.0000
8:91018516:G:C	acceptor_gain	1.0000
8:91018516:G:GC	acceptor_gain	1.0000
8:91021249:CACTT:C	donor_loss	1.0000
8:91021250:ACTTA:A	donor_loss	1.0000
8:91021251:CTTA:C	donor_loss	1.0000
8:91021252:TTA:T	donor_loss	1.0000
8:91021253:T:TG	donor_loss	1.0000
8:91021254:A:AC	donor_gain	1.0000
8:91021255:C:CC	donor_gain	1.0000
8:91021400:CTCCG:C	acceptor_gain	1.0000
8:91021403:CG:C	acceptor_gain	1.0000
8:91021405:C:CC	acceptor_gain	1.0000
8:90996683:T:C	donor_gain	0.9900

AlphaMissense

1651 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:91008762:A:G	C174R	1.000
8:91020173:A:G	C116R	1.000
8:91020205:A:G	L105P	1.000
8:91020208:A:G	L104P	1.000
8:91020217:C:T	C101Y	1.000
8:91020224:A:G	C99R	1.000
8:91021279:A:G	C78R	1.000
8:91021339:A:G	C58R	1.000
8:91008761:C:G	C174S	0.999
8:91008762:A:T	C174S	0.999
8:91018393:G:C	F161L	0.999
8:91018393:G:T	F161L	0.999
8:91018395:A:G	F161L	0.999
8:91018406:C:T	C157Y	0.999
8:91018414:A:C	C154W	0.999
8:91018415:C:T	C154Y	0.999
8:91018416:A:G	C154R	0.999
8:91020158:A:G	C121R	0.999
8:91020166:C:G	R118T	0.999
8:91020171:G:C	C116W	0.999
8:91020172:C:G	C116S	0.999
8:91020172:C:T	C116Y	0.999
8:91020173:A:T	C116S	0.999
8:91020205:A:T	L105H	0.999
8:91020208:A:T	L104H	0.999
8:91020210:A:C	C103W	0.999
8:91020216:A:C	C101W	0.999
8:91020217:C:A	C101F	0.999
8:91020217:C:G	C101S	0.999
8:91020218:A:G	C101R	0.999

dbSNP variants (sampled 300 via entrez): RS1000015540 (8:91004680 G>A), RS1000073242 (8:91020244 G>A,T), RS1000139021 (8:91010635 A>G), RS1000152019 (8:90995442 G>T), RS1000170808 (8:91011081 A>C,G), RS1000264283 (8:91036602 T>C), RS1000404592 (8:91029876 A>G), RS1000435618 (8:91030067 G>A), RS1000470747 (8:91012325 T>A,G), RS1000566371 (8:91038027 T>G), RS1000636161 (8:91036284 T>C), RS1000724823 (8:91031395 T>C), RS1000756150 (8:91031724 T>A), RS1000940267 (8:91025249 G>A), RS1000954229 (8:91017309 G>T)

Disease associations

OMIM: gene MIM:609864 | 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
GCST011703_88	Smoking initiation	2.000000e-09

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	increases expression, decreases expression, increases abundance	3
bisphenol A	decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Valproic Acid	affects expression, decreases methylation, increases expression	2
Particulate Matter	increases abundance, increases expression, decreases expression	2
FR900359	affects phosphorylation	1
triphenyl phosphate	affects expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
trichostatin A	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
di-n-butylphosphoric acid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
ICG 001	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
Temozolomide	decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	decreases expression	1
Leflunomide	increases expression	1
Cisplatin	increases expression	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Potassium Dichromate	increases expression	1
Smoke	decreases expression, increases abundance	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_F0B6	HEK293 TMEM55A/TMEM55B DKO	Transformed cell line	Female

Clinical trials (associated diseases)

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