PLPPR2

Summary

PLPPR2 (phospholipid phosphatase related 2, HGNC:29566) is a protein-coding gene on chromosome 19p13.2, encoding Phospholipid phosphatase-related protein type 2 (Q96GM1).

Predicted to enable phosphatidate phosphatase activity. Predicted to be involved in phospholipid dephosphorylation; phospholipid metabolic process; and signal transduction. Predicted to be located in membrane. Predicted to be active in plasma membrane.

Source: NCBI Gene 64748 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 63 total
• MANE Select transcript: NM_001393892

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29566
Approved symbol	PLPPR2
Name	phospholipid phosphatase related 2
Location	19p13.2
Locus type	gene with protein product
Status	Approved
Aliases	LPPR2, PRG-4
Ensembl gene	ENSG00000105520
Ensembl biotype	protein_coding
OMIM	619591
Entrez	64748

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 3 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000251473, ENST00000586380, ENST00000586431, ENST00000587801, ENST00000588196, ENST00000588360, ENST00000591329, ENST00000591608, ENST00000688289, ENST00000970837, ENST00000970838

RefSeq mRNA: 7 — MANE Select: NM_001393892 NM_001170635, NM_001393892, NM_001393893, NM_001393894, NM_001393895, NM_001393896, NM_022737

CCDS: CCDS12258, CCDS59352, CCDS92519

Canonical transcript exons

ENST00000688289 — 10 exons

Exon	Start	End
ENSE00000680511	11359532	11359720
ENSE00000680514	11359821	11359956
ENSE00001061222	11356802	11356976
ENSE00002209763	11364347	11365698
ENSE00002834936	11363713	11363835
ENSE00003509956	11362513	11362689
ENSE00003550449	11357660	11357739
ENSE00003586679	11361217	11361488
ENSE00003592863	11364161	11364212
ENSE00003935321	11355432	11355572

Expression profiles

Bgee: expression breadth ubiquitous, 246 present calls, max score 96.43.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 25.4766 / max 348.9528, expressed in 1743 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173913	21.9297	1740
173914	3.4340	1237
173915	0.1129	35

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.43	gold quality
adenohypophysis	UBERON:0002196	96.26	gold quality
amygdala	UBERON:0001876	95.98	gold quality
right frontal lobe	UBERON:0002810	95.98	gold quality
nucleus accumbens	UBERON:0001882	95.51	gold quality
anterior cingulate cortex	UBERON:0009835	95.51	gold quality
pituitary gland	UBERON:0000007	95.50	gold quality
cingulate cortex	UBERON:0003027	95.49	gold quality
stromal cell of endometrium	CL:0002255	95.36	gold quality
Ammon’s horn	UBERON:0001954	94.52	gold quality
right hemisphere of cerebellum	UBERON:0014890	94.28	gold quality
hypothalamus	UBERON:0001898	93.92	gold quality
prefrontal cortex	UBERON:0000451	93.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.67	gold quality
lower esophagus	UBERON:0013473	93.65	gold quality
frontal cortex	UBERON:0001870	93.47	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.46	gold quality
left uterine tube	UBERON:0001303	93.35	gold quality
cerebellar hemisphere	UBERON:0002245	93.32	gold quality
temporal lobe	UBERON:0001871	93.30	gold quality
neocortex	UBERON:0001950	93.30	gold quality
cerebellar cortex	UBERON:0002129	93.28	gold quality
caudate nucleus	UBERON:0001873	93.25	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	93.03	gold quality
forebrain	UBERON:0001890	93.00	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.98	gold quality
cerebral cortex	UBERON:0000956	92.89	gold quality
CA1 field of hippocampus	UBERON:0003881	92.82	gold quality
telencephalon	UBERON:0001893	92.80	gold quality
putamen	UBERON:0001874	92.49	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-93593	yes	15.28
E-ANND-3	yes	6.23

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

78 targeting PLPPR2, 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-6748-5P	100.00	65.81	1057
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6752-3P	99.72	66.71	1587
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-3128	99.50	67.85	1258
HSA-MIR-1207-5P	99.49	69.11	2983
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-183-5P	99.31	72.27	1164
HSA-MIR-5589-3P	99.29	68.30	1443

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	plppr2b	ENSDARG00000044600
danio_rerio	plppr2a	ENSDARG00000101478
mus_musculus	Plppr2	ENSMUSG00000040563
rattus_norvegicus	Plppr2	ENSRNOG00000012164
drosophila_melanogaster	wun	FBGN0016078
drosophila_melanogaster	laza	FBGN0037163
drosophila_melanogaster	CG11438	FBGN0037164
drosophila_melanogaster	CG11437	FBGN0037165
drosophila_melanogaster	CG11426	FBGN0037166
drosophila_melanogaster	CG11425	FBGN0037167
drosophila_melanogaster	CG12746	FBGN0037341
drosophila_melanogaster	wun2	FBGN0041087
caenorhabditis_elegans		WBGENE00018756

Paralogs (9): PLPP1 (ENSG00000067113), PLPPR5 (ENSG00000117598), PLPPR4 (ENSG00000117600), PLPPR3 (ENSG00000129951), PLPP2 (ENSG00000141934), PLPP5 (ENSG00000147535), PLPPR1 (ENSG00000148123), PLPP3 (ENSG00000162407), PLPP4 (ENSG00000203805)

Protein

Protein identifiers

Phospholipid phosphatase-related protein type 2 — Q96GM1 (reviewed: Q96GM1)

Alternative names: Inactive phospholipid phosphatase PLPPR2, Lipid phosphate phosphatase-related protein type 2, Plasticity-related gene 4 protein

All UniProt accessions (4): Q96GM1, A0A8I5KWF3, K7EMX8, K7EQF7

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

Similarity. Belongs to the PA-phosphatase related phosphoesterase family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96GM1-1	1	yes
Q96GM1-2	2

RefSeq proteins (7): NP_001164106, NP_001380821, NP_001380822, NP_001380823, NP_001380824, NP_001380825, NP_073574 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR036938	PAP2/HPO_sf	Homologous_superfamily
IPR043216	PAP-like	Family

Pfam: PF01569

Enzyme classification (BRENDA):

• EC 3.1.3.4 — phosphatidate phosphatase (BRENDA: 31 organisms, 190 substrates, 196 inhibitors, 44 Km, 3 kcat entries)

Substrate kinetics (BRENDA)

10 substrates with measured Km, best-characterized 10. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
PHOSPHATIDIC ACID	0.0054–1.2	17
LYSOPHOSPHATIDATE	0.046–0.179	3
PHOSPHATIDATE	0.284–0.369	3
SPHINGOSINE-1-PHOSPHATE	0.028–0.26	3
CERAMIDE-1-PHOSPHATE	0.022–0.052	2
DIACYLGLYCEROL DIPHOSPHATE	0.041–0.104	2
LYSOPHOSPHATIDIC ACID	0.295–0.58	2
1,2-DIACYL-SN-GLYCEROL-3-PHOSPHATE	0.5954	1
2-(4,4-DIFLUORO-5,7-DIMETHYL-4-BORA-3A,4A-DIAZA-	0.024	1
DIOCTANOYL PHOSPHATIDIC ACID	1.4	1

UniProt features (17 total): transmembrane region 6, modified residue 2, splice variant 2, sequence conflict 2, chain 1, glycosylation site 1, sequence variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96GM1-F1	79.10	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 (2): 312, 299

Glycosylation sites (1): 165

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-419408	Lysosphingolipid and LPA receptors

MSigDB gene sets: 123 (showing top): GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, TGACCTY_ERR1_Q2, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, GOBP_LIPID_METABOLIC_PROCESS, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, HFH1_01, GOBP_DEPHOSPHORYLATION, DOUGLAS_BMI1_TARGETS_UP, OCT1_B, SAGIV_CD24_TARGETS_DN, LEIN_LOCALIZED_TO_PROXIMAL_DENDRITES, CTGAGCC_MIR24

GO Biological Process (3): phospholipid metabolic process (GO:0006644), signal transduction (GO:0007165), phospholipid dephosphorylation (GO:0046839)

GO Molecular Function (2): phosphatidate phosphatase activity (GO:0008195), protein binding (GO:0005515)

GO Cellular Component (2): plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
lipid metabolic process	1
organophosphate metabolic process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
dephosphorylation	1
lipid modification	1
lipid phosphatase activity	1
binding	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

960 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPPR2	CCDC159	P0C7I6	506
PLPPR2	FRAT2	O75474	483
PLPPR2	TMEM125	Q96AQ2	469
PLPPR2	CLDN19	Q8N6F1	464
PLPPR2	IER2	Q9BTL4	461
PLPPR2	SWSAP1	Q6NVH7	449
PLPPR2	COL9A2	Q14055	446
PLPPR2	DOLPP1	Q86YN1	434
PLPPR2	E5RHQ9	E5RHQ9	432
PLPPR2	FZD10	Q9ULW2	422
PLPPR2	TAFA5	Q7Z5A7	408
PLPPR2	TAL1	P17542	403
PLPPR2	FAM241B	Q96D05	400
PLPPR2	C3orf62	Q6ZUJ4	394
PLPPR2	TMEM51	Q9NW97	376

IntAct

71 interactions, top by confidence:

A	B	Type	Score
CLDN9	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
STX12	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	TMEM237	psi-mi:“MI:0915”(physical association)	0.560
CREB3L1	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	MARCHF2	psi-mi:“MI:0915”(physical association)	0.560
KIR2DL3	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	SLC19A3	psi-mi:“MI:0915”(physical association)	0.560
SMAGP	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	SCN3B	psi-mi:“MI:0915”(physical association)	0.560
LYPD5	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
SSMEM1	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	UBE2J1	psi-mi:“MI:0915”(physical association)	0.560
	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
CD79A	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	VSIR	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	SIGLEC12	psi-mi:“MI:0915”(physical association)	0.560
GYPC	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	TMED9	psi-mi:“MI:0915”(physical association)	0.560
CLDN5	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
ARL13B	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
CISD2	PLPPR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	CIAO2A	psi-mi:“MI:0915”(physical association)	0.560
PLPPR2	METAP2	psi-mi:“MI:0914”(association)	0.530
PLPPR2	SEC24D	psi-mi:“MI:0914”(association)	0.350
PLPPR2	BCL2L1	psi-mi:“MI:0914”(association)	0.350

BioGRID (99): RNF214 (Affinity Capture-MS), METAP2 (Affinity Capture-MS), TTC5 (Affinity Capture-MS), YTHDF1 (Affinity Capture-MS), DPP9 (Affinity Capture-MS), PCDH9 (Affinity Capture-MS), DNAJC12 (Affinity Capture-MS), TUBG1 (Affinity Capture-MS), SPC24 (Affinity Capture-MS), ISCA1 (Affinity Capture-MS), METAP1 (Affinity Capture-MS), ARF5 (Affinity Capture-MS), C9orf40 (Affinity Capture-MS), SAR1B (Affinity Capture-MS), SEC24D (Affinity Capture-MS)

ESM2 similar proteins: A4IFN5, A6NDV4, B1AWJ5, B1AZA5, B2LYG4, P59266, Q05B45, Q0VCJ8, Q3KRC4, Q3UMZ3, Q5EA70, Q5H8A4, Q5QJU3, Q5RBJ7, Q5U3C3, Q5VTY9, Q5ZMH6, Q6PHN7, Q6TCH4, Q6W5G4, Q6ZVK1, Q7Z7J7, Q865K8, Q86WK9, Q8BHH9, Q8BMT9, Q8BWB6, Q8C1E7, Q8K3J9, Q8N6M3, Q8NBT3, Q8NEB5, Q8NFT2, Q8VCW4, Q8VCY8, Q8VD53, Q8VDI9, Q96GM1, Q9BSA9, Q9BXJ8

Diamond homologs: A4II83, Q29RT8, Q32ZL2, Q3SZE3, Q6GM05, Q6GQ62, Q6IQH6, Q6T4P5, Q6W5G4, Q6WAY2, Q7TMB0, Q7TMB7, Q7TME0, Q7TPB0, Q7Z2D5, Q8BFZ2, Q8BJ52, Q8TBJ4, Q8VCY8, Q96GM1, O14495, P97544, Q8K593, Q99JY8, Q9DAX2, Q5FVJ3, Q91WB2, Q9ZU49, Q0WNG6, O08564, O88956, P60588, Q05521, Q61469, Q8LFD1

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	50
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1795 predictions. Top by Δscore:

Variant	Effect	Δscore
19:11355570:GCG:G	donor_gain	1.0000
19:11359500:C:CA	acceptor_gain	1.0000
19:11359504:A:AG	acceptor_gain	1.0000
19:11359505:C:G	acceptor_gain	1.0000
19:11359513:C:CA	acceptor_gain	1.0000
19:11359518:T:TA	acceptor_gain	1.0000
19:11359519:G:A	acceptor_gain	1.0000
19:11359717:CACG:C	donor_loss	1.0000
19:11359719:CGG:C	donor_loss	1.0000
19:11359721:G:GG	donor_gain	1.0000
19:11359721:GTG:G	donor_loss	1.0000
19:11359722:T:G	donor_loss	1.0000
19:11359819:A:AG	acceptor_gain	1.0000
19:11359820:G:GA	acceptor_gain	1.0000
19:11361215:A:AG	acceptor_gain	1.0000
19:11361216:G:GG	acceptor_gain	1.0000
19:11361486:GCG:G	donor_gain	1.0000
19:11362687:TTGG:T	donor_loss	1.0000
19:11362688:TGG:T	donor_loss	1.0000
19:11362689:GGT:G	donor_loss	1.0000
19:11362690:G:A	donor_loss	1.0000
19:11362690:G:GG	donor_gain	1.0000
19:11362691:TGA:T	donor_loss	1.0000
19:11362692:GAG:G	donor_loss	1.0000
19:11363706:A:AG	acceptor_gain	1.0000
19:11363709:CCA:C	acceptor_loss	1.0000
19:11363711:A:AG	acceptor_gain	1.0000
19:11363711:A:T	acceptor_loss	1.0000
19:11363712:G:GA	acceptor_gain	1.0000
19:11363712:GGT:G	acceptor_gain	1.0000

AlphaMissense

2845 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:11361298:T:G	F158C	0.999
19:11362666:G:T	G273W	0.999
19:11361232:G:A	G136D	0.998
19:11361297:T:C	F158L	0.998
19:11361298:T:C	F158S	0.998
19:11361299:C:A	F158L	0.998
19:11361299:C:G	F158L	0.998
19:11362667:G:A	G273E	0.998
19:11361231:G:C	G136R	0.997
19:11362655:G:A	G269D	0.997
19:11361309:T:A	C162S	0.996
19:11361310:G:A	C162Y	0.996
19:11361310:G:C	C162S	0.996
19:11361438:T:C	F205L	0.996
19:11361440:C:A	F205L	0.996
19:11361440:C:G	F205L	0.996
19:11362628:G:C	R260P	0.996
19:11362654:G:C	G269R	0.996
19:11362666:G:A	G273R	0.996
19:11362666:G:C	G273R	0.996
19:11359610:T:C	F49L	0.995
19:11359612:C:A	F49L	0.995
19:11359612:C:G	F49L	0.995
19:11359616:T:A	C51S	0.995
19:11359617:G:C	C51S	0.995
19:11361309:T:C	C162R	0.995
19:11363734:T:C	F288L	0.995
19:11363736:T:A	F288L	0.995
19:11363736:T:G	F288L	0.995
19:11359611:T:C	F49S	0.994

dbSNP variants (sampled 300 via entrez): RS1000025922 (19:11359075 C>A,G,T), RS1000171966 (19:11364067 T>C), RS1000172972 (19:11354992 C>A,T), RS1000260387 (19:11357092 C>T), RS1000313128 (19:11356882 G>A,T), RS1000597811 (19:11355927 G>T), RS1000651625 (19:11355520 C>T), RS1000754772 (19:11357695 C>G,T), RS1001634681 (19:11363431 C>G), RS1001760200 (19:11364718 C>G,T), RS1001872544 (19:11363315 T>G), RS1002502011 (19:11363530 G>A), RS1003167868 (19:11366068 G>C), RS1003319402 (19:11355686 G>A), RS1003370252 (19:11362321 C>CA,CG)

Disease associations

OMIM: gene MIM:619591 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs7251786	CCDC159, PLPPR2, TMEM205		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression, decreases expression	3
bisphenol A	increases expression, affects cotreatment, increases methylation	2
Arsenic	increases abundance, increases expression, decreases expression, affects cotreatment	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
o,p’-DDT	increases expression	1
manganese chloride	increases abundance, increases expression, affects cotreatment	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	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	decreases expression	1
Resveratrol	increases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diazinon	increases methylation	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	increases methylation	1
Ozone	affects expression, increases abundance	1
Smoke	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Urethane	increases expression	1

Clinical trials (associated diseases)

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