PLPPR3

Summary

PLPPR3 (phospholipid phosphatase related 3, HGNC:23497) is a protein-coding gene on chromosome 19p13.3, encoding Phospholipid phosphatase-related protein type 3 (Q6T4P5).

The proteins in the lipid phosphate phosphatase (LPP) family, including PRG2, are integral membrane proteins that modulate bioactive lipid phosphates including phosphatidate, lysophosphatidate, and sphingosine-1-phosphate in the context of cell migration, neurite retraction, and mitogenesis (Brauer et al., 2003 [PubMed 12730698]).

Source: NCBI Gene 79948 — RefSeq curated summary.

At a glance

• GWAS associations: 12
• Clinical variants (ClinVar): 183 total
• MANE Select transcript: NM_001270366

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23497
Approved symbol	PLPPR3
Name	phospholipid phosphatase related 3
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	PRG-2, FLJ11535, LPPR3, PRG2
Ensembl gene	ENSG00000129951
Ensembl biotype	protein_coding
OMIM	610391
Entrez	79948

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000359894, ENST00000517665, ENST00000519502, ENST00000520876, ENST00000932446, ENST00000932447, ENST00000932448, ENST00000947290

RefSeq mRNA: 2 — MANE Select: NM_001270366 NM_001270366, NM_024888

CCDS: CCDS12043, CCDS58636

Canonical transcript exons

ENST00000520876 — 8 exons

Exon	Start	End
ENSE00001666503	812488	813895
ENSE00001668788	821915	821955
ENSE00001775617	814886	815081
ENSE00002277015	821485	821585
ENSE00002851219	815666	815851
ENSE00003505698	815186	815327
ENSE00004026201	814434	814607
ENSE00004026203	814692	814749

Expression profiles

Bgee: expression breadth ubiquitous, 142 present calls, max score 97.79.

FANTOM5 (CAGE): breadth broad, TPM avg 13.4422 / max 462.1986, expressed in 732 samples.

FANTOM5 promoters (11 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177933	7.3452	560
177934	2.7687	563
177939	1.3911	367
177935	0.4629	76
177940	0.3746	118
177937	0.3109	123
177930	0.2849	162
177938	0.1830	60
177932	0.1735	109
177936	0.0773	26

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	97.79	gold quality
ganglionic eminence	UBERON:0004023	94.99	gold quality
right uterine tube	UBERON:0001302	94.94	gold quality
nucleus accumbens	UBERON:0001882	88.31	gold quality
anterior cingulate cortex	UBERON:0009835	88.07	gold quality
cingulate cortex	UBERON:0003027	87.91	gold quality
ventricular zone	UBERON:0003053	86.77	gold quality
amygdala	UBERON:0001876	85.44	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	85.10	gold quality
embryo	UBERON:0000922	83.31	gold quality
right frontal lobe	UBERON:0002810	83.14	gold quality
caudate nucleus	UBERON:0001873	83.11	gold quality
putamen	UBERON:0001874	81.96	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	81.66	gold quality
prefrontal cortex	UBERON:0000451	81.25	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.10	gold quality
neocortex	UBERON:0001950	80.57	gold quality
telencephalon	UBERON:0001893	79.76	gold quality
hypothalamus	UBERON:0001898	79.31	gold quality
cerebral cortex	UBERON:0000956	79.03	gold quality
frontal cortex	UBERON:0001870	78.92	gold quality
Ammon’s horn	UBERON:0001954	78.13	gold quality
temporal lobe	UBERON:0001871	77.37	gold quality
forebrain	UBERON:0001890	76.64	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	73.36	gold quality
brain	UBERON:0000955	72.48	gold quality
buccal mucosa cell	CL:0002336	71.61	gold quality
superior frontal gyrus	UBERON:0002661	69.57	gold quality
bone marrow	UBERON:0002371	69.49	gold quality
right lung	UBERON:0002167	68.38	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.88

Regulation

Is transcription factor: no

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	plppr3a	ENSDARG00000010144
danio_rerio	plppr3b	ENSDARG00000028552
mus_musculus	Plppr3	ENSMUSG00000035835
rattus_norvegicus	Plppr3	ENSRNOG00000027940
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), PLPPR2 (ENSG00000105520), PLPPR5 (ENSG00000117598), PLPPR4 (ENSG00000117600), PLPP2 (ENSG00000141934), PLPP5 (ENSG00000147535), PLPPR1 (ENSG00000148123), PLPP3 (ENSG00000162407), PLPP4 (ENSG00000203805)

Protein

Protein identifiers

Phospholipid phosphatase-related protein type 3 — Q6T4P5 (reviewed: Q6T4P5)

Alternative names: Inactive phospholipid phosphatase PLPPR3, Lipid phosphate phosphatase-related protein type 3, PAP-2-like protein 2, Plasticity-related gene 2 protein

All UniProt accessions (3): Q6T4P5, H0YBY4, K7ELK5

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Membrane.

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

Isoforms (4)

UniProt ID	Names	Canonical?
Q6T4P5-1	1, PRG-2a	yes
Q6T4P5-2	2
Q6T4P5-3	3, PRG-2b
Q6T4P5-4	4

RefSeq proteins (2): NP_001257295, NP_079164 (=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 (28 total): transmembrane region 6, modified residue 6, region of interest 4, compositionally biased region 4, splice variant 3, glycosylation site 2, sequence variant 2, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6T4P5-F1	59.17	0.20

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 (6): 322, 353, 376, 428, 508, 641

Glycosylation sites (2): 169, 318

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-419408	Lysosphingolipid and LPA receptors

MSigDB gene sets: 200 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_LIPID_MODIFICATION, MULLIGHAN_NPM1_SIGNATURE_3_UP, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, REACTOME_INNATE_IMMUNE_SYSTEM, GOCC_SECRETORY_GRANULE, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, TGACCTY_ERR1_Q2, MODULE_16, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_ERYTHROCYTE_UP, MODULE_75, GOBP_NEGATIVE_REGULATION_OF_MULTICELLULAR_ORGANISMAL_PROCESS

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

GO Molecular Function (1): phosphatidate phosphatase activity (GO:0008195)

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
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

840 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPPR3	ADCY1	Q08828	649
PLPPR3	PTH	P01270	582
PLPPR3	GNAS	Q5JWF2	562
PLPPR3	STX16	O14662	560
PLPPR3	TSPAN33	Q86UF1	529
PLPPR3	TMEM259	Q4ZIN3	499
PLPPR3	MED16	Q9Y2X0	468
PLPPR3	GRIN3B	O60391	436
PLPPR3	ANKRD13B	Q86YJ7	434
PLPPR3	TMEM25	Q86YD3	431
PLPPR3	TMEM91	Q6ZNR0	424
PLPPR3	SUCLG1	P53597	423
PLPPR3	PIP5KL1	Q5T9C9	364
PLPPR3	R3HDM4	Q96D70	360
PLPPR3	VPS8	Q8N3P4	352

IntAct

27 interactions, top by confidence:

A	B	Type	Score
ADGRG5	KLRG2	psi-mi:“MI:0914”(association)	0.530
PLPPR1	STXBP3	psi-mi:“MI:0914”(association)	0.530
CHRND	TPST2	psi-mi:“MI:0914”(association)	0.530
PLPPR3	GPR182	psi-mi:“MI:0915”(physical association)	0.370
PLPPR3	DRD2	psi-mi:“MI:0915”(physical association)	0.370
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CACNA1C	IGLL5	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POTEF	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	IGLON5	psi-mi:“MI:0914”(association)	0.350
HCN1	POTEF	psi-mi:“MI:0914”(association)	0.350
CHRNA4	TMEM223	psi-mi:“MI:0914”(association)	0.350
SIDT2	KLRG2	psi-mi:“MI:0914”(association)	0.350
NKAIN1	GPR89A	psi-mi:“MI:0914”(association)	0.350
HTR3A	EXTL3	psi-mi:“MI:0914”(association)	0.350
KLHL22	TRAV18	psi-mi:“MI:0914”(association)	0.350
SLC4A5	ESYT2	psi-mi:“MI:0914”(association)	0.350
MAPT	PITPNM1	psi-mi:“MI:2364”(proximity)	0.270
MAPT	DCTN6	psi-mi:“MI:2364”(proximity)	0.270
MAPT		psi-mi:“MI:2364”(proximity)	0.270
PLPPR3	BAG6	psi-mi:“MI:0915”(physical association)	0.000
STRN4	PLPPR3	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), BAG6 (Two-hybrid), LPPR3 (Two-hybrid), LPPR3 (Two-hybrid), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS)

ESM2 similar proteins: A2A7Q9, F1LXF1, O08873, O14795, O35274, O46606, P11274, P12755, P22681, P22682, P49797, P50636, Q08B84, Q0VGY8, Q1L8L6, Q2VJ60, Q3UR85, Q3YEC7, Q4KUS2, Q60698, Q62768, Q69ZT9, Q6PAJ1, Q6R891, Q6T4P5, Q6ZMZ0, Q6ZWB6, Q7TMB0, Q7TPB0, Q80U28, Q86YJ5, Q8HXH0, Q8NEL9, Q8TEK3, Q8WXG6, Q8WXH2, Q92622, Q92625, Q96SB3, Q9CXG9

Diamond homologs: A4II83, Q29RT8, Q32ZL2, Q3SZE3, Q6GM05, Q6GQ62, Q6IQH6, Q6T4P5, Q6W5G4, Q6WAY2, Q7TMB0, Q7TMB7, Q7TME0, Q7TPB0, Q7Z2D5, Q8BFZ2, Q8BJ52, Q8TBJ4, Q8VCY8, Q96GM1, O08564, O14494, O14495, O43688, O88956, P60588, P97544, Q04396, Q0WNG6, Q10022, Q2HJ61, Q3UMZ3, Q54PR7, Q61469, Q86AF0, Q8K593, Q8LFD1, Q8NEB5, Q99JY8, Q9DAX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	175
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1022 predictions. Top by Δscore:

Variant	Effect	Δscore
19:813891:CAGGC:C	acceptor_gain	1.0000
19:813893:GGC:G	acceptor_gain	1.0000
19:813893:GGCCT:G	acceptor_loss	1.0000
19:813894:GC:G	acceptor_gain	1.0000
19:813894:GCCTG:G	acceptor_loss	1.0000
19:813895:CC:C	acceptor_gain	1.0000
19:813896:C:CC	acceptor_gain	1.0000
19:813896:CTGT:C	acceptor_loss	1.0000
19:813897:T:A	acceptor_loss	1.0000
19:814429:CTCA:C	donor_loss	1.0000
19:814431:CA:C	donor_loss	1.0000
19:814432:A:AC	donor_gain	1.0000
19:814432:AC:A	donor_gain	1.0000
19:814432:ACCAG:A	donor_loss	1.0000
19:814433:C:CT	donor_gain	1.0000
19:814433:CC:C	donor_gain	1.0000
19:814433:CCAGG:C	donor_gain	1.0000
19:814605:CAT:C	acceptor_gain	1.0000
19:815810:C:CT	acceptor_gain	1.0000
19:815811:A:T	acceptor_gain	1.0000
19:815816:G:C	acceptor_gain	1.0000
19:815849:CAG:C	acceptor_gain	1.0000
19:815852:C:CC	acceptor_gain	1.0000
19:813892:AGGC:A	acceptor_gain	0.9900
19:813900:C:CT	acceptor_gain	0.9900
19:813901:G:T	acceptor_gain	0.9900
19:814430:TCA:T	donor_gain	0.9900
19:814431:CAC:C	donor_gain	0.9900
19:814433:CCA:C	donor_gain	0.9900
19:814433:CCAG:C	donor_gain	0.9900

AlphaMissense

4609 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:814987:G:C	C166W	1.000
19:814988:C:T	C166Y	1.000
19:814989:A:G	C166R	1.000
19:814456:C:T	G270E	0.999
19:814457:C:A	G270W	0.999
19:814457:C:G	G270R	0.999
19:814457:C:T	G270R	0.999
19:814468:C:T	G266D	0.999
19:814469:C:G	G266R	0.999
19:814710:G:C	F213L	0.999
19:814710:G:T	F213L	0.999
19:814712:A:G	F213L	0.999
19:814738:G:T	P204Q	0.999
19:814740:G:C	F203L	0.999
19:814740:G:T	F203L	0.999
19:814742:A:G	F203L	0.999
19:814921:G:C	C188W	0.999
19:814922:C:G	C188S	0.999
19:814922:C:T	C188Y	0.999
19:814923:A:G	C188R	0.999
19:814923:A:T	C188S	0.999
19:814988:C:A	C166F	0.999
19:814988:C:G	C166S	0.999
19:814989:A:T	C166S	0.999
19:815063:A:G	L141P	0.999
19:815066:C:T	G140D	0.999
19:815067:C:G	G140R	0.999
19:815190:A:C	F133L	0.999
19:815190:A:T	F133L	0.999
19:815192:A:G	F133L	0.999

dbSNP variants (sampled 300 via entrez): RS1000037722 (19:822050 C>G,T), RS1000050520 (19:813985 CG>C,CGG), RS1000106016 (19:822831 G>A,C), RS1000134201 (19:825696 G>T), RS1000187086 (19:825590 T>G), RS1000334943 (19:813377 CTCTTCG>C), RS1000430101 (19:822142 C>T), RS1000507877 (19:813608 G>A), RS1000623747 (19:813798 C>A,T), RS1000932984 (19:822639 A>C), RS1001008220 (19:822801 G>A,C), RS1001167231 (19:818074 G>C), RS1001405703 (19:817952 G>A), RS1001551697 (19:816258 C>A,G), RS1001609628 (19:812739 G>A)

Disease associations

OMIM: gene MIM:610391 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

12 associations (top):

Study	Trait	p-value
GCST006288_369	Heel bone mineral density	4.000000e-10
GCST006288_669	Heel bone mineral density	5.000000e-16
GCST006288_70	Heel bone mineral density	1.000000e-07
GCST006979_736	Heel bone mineral density	8.000000e-33
GCST008062_33	Blood urea nitrogen levels	3.000000e-09
GCST009723_20	Vertical cup-disc ratio (adjusted for vertical disc diameter)	7.000000e-11
GCST010002_145	Refractive error	1.000000e-11
GCST010083_286	Hemoglobin levels	9.000000e-27
GCST90002385_294	High light scatter reticulocyte count	6.000000e-17
GCST90002386_92	High light scatter reticulocyte percentage of red cells	6.000000e-10
GCST90002405_569	Reticulocyte count	1.000000e-11
GCST90002406_518	Reticulocyte fraction of red cells	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0006939	cup-to-disc ratio measurement
EFO:0004509	hemoglobin measurement
EFO:0007986	reticulocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, increases methylation	2
Cisplatin	increases expression, decreases expression, affects cotreatment	2
propionaldehyde	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression	1
abrine	decreases expression	1
licochalcone B	increases expression	1
jinfukang	affects cotreatment, increases expression	1
Sunitinib	decreases expression	1
Vorinostat	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Lipopolysaccharides	affects cotreatment, decreases expression	1
Silicon Dioxide	decreases expression	1
Thimerosal	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Triclosan	increases expression	1
Valproic Acid	increases methylation	1
Okadaic Acid	increases expression	1
Particulate Matter	increases abundance, increases expression	1

Clinical trials (associated diseases)

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