PLPPR1

Summary

PLPPR1 (phospholipid phosphatase related 1, HGNC:25993) is a protein-coding gene on chromosome 9q31.1, encoding Phospholipid phosphatase-related protein type 1 (Q8TBJ4). May play a role in neurite outgrowth and neurogenesis.

This gene encodes a member of the plasticity-related gene (PRG) family. Members of the PRG family mediate lipid phosphate phosphatase activity in neurons and are known to be involved in neuronal plasticity. The protein encoded by this gene does not perform its function through enzymatic phospholipid degradation. This gene is strongly expressed in brain. It shows dynamic expression regulation during brain development and neuronal excitation. Alternatively spliced transcript variants encoding the same protein have been observed.

Source: NCBI Gene 54886 — RefSeq curated summary.

At a glance

• GWAS associations: 8
• Clinical variants (ClinVar): 39 total
• MANE Select transcript: NM_207299

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25993
Approved symbol	PLPPR1
Name	phospholipid phosphatase related 1
Location	9q31.1
Locus type	gene with protein product
Status	Approved
Aliases	PRG-3, MGC26189, FLJ20300, LPPR1
Ensembl gene	ENSG00000148123
Ensembl biotype	protein_coding
OMIM	619590
Entrez	54886

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 8 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000374874, ENST00000395056, ENST00000456287, ENST00000463206, ENST00000494890, ENST00000883511, ENST00000883512, ENST00000883513, ENST00000883514, ENST00000883515

RefSeq mRNA: 2 — MANE Select: NM_207299 NM_017753, NM_207299

CCDS: CCDS6751

Canonical transcript exons

ENST00000374874 — 8 exons

Exon	Start	End
ENSE00000983241	101269880	101270068
ENSE00000983244	101312798	101312974
ENSE00000983245	101317365	101317496
ENSE00001464925	101324025	101325135
ENSE00001464945	101028727	101029102
ENSE00003462594	101185450	101185557
ENSE00003587838	101286104	101286236
ENSE00003611424	101309211	101309461

Expression profiles

Bgee: expression breadth broad, 99 present calls, max score 96.99.

FANTOM5 (CAGE): breadth broad, TPM avg 5.3127 / max 508.9128, expressed in 347 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
97741	2.2433	278
97742	0.9559	221
97751	0.8597	100
97739	0.2195	94
97745	0.1997	66
97744	0.1590	69
97747	0.1220	63
205582	0.1086	63
97746	0.1010	41
97740	0.0972	43

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	96.99	gold quality
corpus callosum	UBERON:0002336	96.84	gold quality
ganglionic eminence	UBERON:0004023	96.73	gold quality
nucleus accumbens	UBERON:0001882	89.99	gold quality
ventricular zone	UBERON:0003053	89.30	gold quality
amygdala	UBERON:0001876	88.01	gold quality
temporal lobe	UBERON:0001871	87.95	gold quality
Ammon’s horn	UBERON:0001954	87.79	gold quality
caudate nucleus	UBERON:0001873	87.57	gold quality
putamen	UBERON:0001874	87.56	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.82	gold quality
prefrontal cortex	UBERON:0000451	85.21	gold quality
substantia nigra	UBERON:0002038	84.07	gold quality
primary visual cortex	UBERON:0002436	83.17	gold quality
cerebral cortex	UBERON:0000956	82.81	gold quality
hypothalamus	UBERON:0001898	82.80	gold quality
adult mammalian kidney	UBERON:0000082	82.28	gold quality
frontal cortex	UBERON:0001870	82.10	gold quality
superior frontal gyrus	UBERON:0002661	82.02	gold quality
Brodmann (1909) area 9	UBERON:0013540	81.74	gold quality
anterior cingulate cortex	UBERON:0009835	81.70	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	80.81	gold quality
kidney	UBERON:0002113	78.59	gold quality
brain	UBERON:0000955	78.39	gold quality
right frontal lobe	UBERON:0002810	77.49	gold quality
islet of Langerhans	UBERON:0000006	74.62	gold quality
liver	UBERON:0002107	73.12	gold quality
right lobe of liver	UBERON:0001114	72.74	gold quality
metanephros cortex	UBERON:0010533	70.17	gold quality
cortex of kidney	UBERON:0001225	68.31	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 7.

Experiment	Marker?	Max mean expression
E-GEOD-83139	yes	122.12
E-HCAD-35	yes	55.50
E-GEOD-84465	yes	24.46
E-HCAD-25	yes	17.28
E-ENAD-27	yes	8.20
E-GEOD-93593	yes	4.07
E-ANND-3	yes	3.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

110 targeting PLPPR1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
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-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-570-3P	99.96	72.41	4910
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-153-5P	99.89	73.86	6317

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	plppr1	ENSDARG00000100642
mus_musculus	Plppr1	ENSMUSG00000063446
rattus_norvegicus	Plppr1	ENSRNOG00000007575
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), PLPPR3 (ENSG00000129951), PLPP2 (ENSG00000141934), PLPP5 (ENSG00000147535), PLPP3 (ENSG00000162407), PLPP4 (ENSG00000203805)

Protein

Protein identifiers

Phospholipid phosphatase-related protein type 1 — Q8TBJ4 (reviewed: Q8TBJ4)

Alternative names: Inactive 2-lysophosphatidate phosphatase PLPPR1, Lipid phosphate phosphatase-related protein type 1, Plasticity-related gene 3 protein

All UniProt accessions (2): Q8TBJ4, M9MML5

UniProt curated annotations — full annotation on UniProt →

Function. May play a role in neurite outgrowth and neurogenesis.

Subcellular location. Cell membrane. Cell projection. Neuron projection.

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

RefSeq proteins (2): NP_060223, NP_997182* (*=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 (12 total): transmembrane region 6, glycosylation site 3, chain 1, sequence conflict 1, modified residue 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8TBJ4-F1	79.06	0.53

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 (1): 307

Glycosylation sites (3): 316, 5, 163

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-419408	Lysosphingolipid and LPA receptors

MSigDB gene sets: 135 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_UP, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BENPORATH_ES_WITH_H3K27ME3, GAANYNYGACNY_UNKNOWN, GCANCTGNY_MYOD_Q6, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, RODWELL_AGING_KIDNEY_NO_BLOOD_DN, COUP_01, SOX9_B1, HNF4_DR1_Q3, HNF4_01, PPAR_DR1_Q2, GOBP_LIPID_METABOLIC_PROCESS

GO Biological Process (4): phospholipid metabolic process (GO:0006644), signal transduction (GO:0007165), nervous system development (GO:0007399), phospholipid dephosphorylation (GO:0046839)

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

GO Cellular Component (5): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), neuron projection (GO:0043005), membrane (GO:0016020), cell projection (GO:0042995)

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
cellular anatomical structure	3
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
system development	1
dephosphorylation	1
lipid modification	1
lipid phosphatase activity	1
binding	1
nuclear lumen	1
membrane	1
cell periphery	1
plasma membrane bounded cell projection	1

Protein interactions and networks

STRING

872 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPPR1	MRPL50	Q8N5N7	559
PLPPR1	NGEF	Q8N5V2	382
PLPPR1	LPAR1	P78351	370
PLPPR1	OR5H1	A6NKK0	370
PLPPR1	ADGRG1	Q9Y653	356
PLPPR1	SPDYC	Q5MJ68	352
PLPPR1	EPHX2	P34913	345
PLPPR1	WDR17	Q8IZU2	340
PLPPR1	CYLC2	Q14093	335
PLPPR1	TTC3	P78477	328
PLPPR1	RBM46	Q8TBY0	326
PLPPR1	OPN3	Q9H1Y3	325
PLPPR1	GRIN3A	Q8TCU5	314
PLPPR1	CASKIN2	Q8WXE0	311
PLPPR1	GAL3ST1	Q99999	307
PLPPR1	CACNA2D2	Q9NY47	307

IntAct

49 interactions, top by confidence:

A	B	Type	Score
TMPPE	PLPPR1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	SLC30A2	psi-mi:“MI:0915”(physical association)	0.560
LEPROT	PLPPR1	psi-mi:“MI:0915”(physical association)	0.560
PLN	PLPPR1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	SERP1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	BDNF	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	SERPINH1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	GRN	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	PECAM1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	PEX1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	PRPS1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	RAD23A	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	TGFBR2	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	WFS1	psi-mi:“MI:0915”(physical association)	0.560
PLPPR1	KIF1B	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (34): LPPR3 (Affinity Capture-MS), STX4 (Affinity Capture-MS), LSG1 (Affinity Capture-MS), STXBP3 (Affinity Capture-MS), RAP1B (Affinity Capture-MS), RAB23 (Affinity Capture-MS), RIOK1 (Affinity Capture-MS), TTC33 (Affinity Capture-MS), TTK (Affinity Capture-MS), JAG2 (Affinity Capture-MS), GTF2F1 (Affinity Capture-MS), LPPR3 (Affinity Capture-MS), RAB23 (Affinity Capture-MS), JAG2 (Affinity Capture-MS), STX4 (Affinity Capture-MS)

ESM2 similar proteins: A0A0G2K1Q8, A0A6I8PMZ8, A0JP80, A2AWR3, A4II83, A5D7L5, E1BPQ3, E9PU17, E9PX95, F5H094, O14495, O42153, P41180, P48442, P49190, P58872, P58873, P97544, Q10022, Q15043, Q20696, Q20735, Q32ZL2, Q3SZE3, Q52KL1, Q54PR7, Q5R9A7, Q5RAB7, Q6AX73, Q6GM05, Q6IQH6, Q6WAY2, Q75N73, Q7Z3F1, Q810K3, Q84M24, Q86UG4, Q8BFZ2, Q8BJ52, Q8C0X7

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, Q8K593, Q8LFD1, Q8NEB5, Q99JY8, Q9DAX2, Q9V576

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PLPPR1	“up-regulates activity”	RASGEF1B	binding
PLPPR1	“up-regulates activity”	RASGEF1A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	34
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2511 predictions. Top by Δscore:

Variant	Effect	Δscore
9:101185448:A:AG	acceptor_gain	1.0000
9:101185449:G:GC	acceptor_gain	1.0000
9:101185554:TGAG:T	donor_loss	1.0000
9:101185555:GAGG:G	donor_loss	1.0000
9:101185556:AGGTA:A	donor_loss	1.0000
9:101185558:G:GA	donor_loss	1.0000
9:101185559:T:A	donor_loss	1.0000
9:101270064:CTATT:C	donor_gain	1.0000
9:101270065:TATT:T	donor_gain	1.0000
9:101270067:TT:T	donor_gain	1.0000
9:101270068:TGT:T	donor_loss	1.0000
9:101270069:G:A	donor_loss	1.0000
9:101270069:G:GG	donor_gain	1.0000
9:101270070:T:A	donor_loss	1.0000
9:101312793:TCCA:T	acceptor_loss	1.0000
9:101312796:A:AG	acceptor_gain	1.0000
9:101312796:A:C	acceptor_loss	1.0000
9:101312796:AGAT:A	acceptor_gain	1.0000
9:101312797:G:GT	acceptor_gain	1.0000
9:101312797:GAT:G	acceptor_gain	1.0000
9:101312797:GATG:G	acceptor_gain	1.0000
9:101312797:GATGT:G	acceptor_gain	1.0000
9:101312973:TGGTA:T	donor_loss	1.0000
9:101312975:G:GG	donor_gain	1.0000
9:101312976:T:A	donor_loss	1.0000
9:101029098:GGGAG:G	donor_gain	0.9900
9:101029099:GGAG:G	donor_gain	0.9900
9:101029099:GGAGG:G	donor_gain	0.9900
9:101029100:GAGG:G	donor_gain	0.9900
9:101029100:GAGGT:G	donor_loss	0.9900

AlphaMissense

2116 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:101309225:G:A	G134R	0.999
9:101309225:G:C	G134R	0.999
9:101309226:G:A	G134E	0.999
9:101309303:T:A	C160S	0.999
9:101309304:G:C	C160S	0.999
9:101309435:A:C	S204R	0.999
9:101309437:C:A	S204R	0.999
9:101309437:C:G	S204R	0.999
9:101312951:G:C	G264R	0.999
9:101309273:G:T	G150W	0.998
9:101309303:T:C	C160R	0.998
9:101309304:G:A	C160Y	0.998
9:101309305:C:G	C160W	0.998
9:101309369:T:A	C182S	0.998
9:101309370:G:C	C182S	0.998
9:101312801:T:G	Y214D	0.998
9:101312939:G:C	G260R	0.998
9:101312940:G:A	G260D	0.998
9:101312952:G:A	G264D	0.998
9:101270058:C:G	P81R	0.997
9:101286230:T:C	F127L	0.997
9:101286232:C:A	F127L	0.997
9:101286232:C:G	F127L	0.997
9:101309226:G:T	G134V	0.997
9:101309291:T:C	F156L	0.997
9:101309292:T:G	F156C	0.997
9:101309293:C:A	F156L	0.997
9:101309293:C:G	F156L	0.997
9:101309371:T:G	C182W	0.997
9:101309403:G:C	R193P	0.997

dbSNP variants (sampled 300 via entrez): RS1000002741 (9:101114306 T>G), RS1000015703 (9:101148889 C>G,T), RS1000022570 (9:101095021 G>A), RS1000024843 (9:101108493 A>G), RS1000031863 (9:101310845 T>C,G), RS1000050780 (9:101273898 T>C,G), RS1000052328 (9:101058567 A>G), RS1000083804 (9:101311053 T>C), RS1000085773 (9:101099431 G>A), RS1000089716 (9:101311826 A>G), RS1000098025 (9:101109584 C>T), RS1000100894 (9:101121248 C>T), RS1000111838 (9:101164876 C>A), RS1000114110 (9:101191762 A>G), RS1000134054 (9:101083094 C>G,T)

Disease associations

OMIM: gene MIM:619590 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST003174_16	Sense of smell	5.000000e-06
GCST003174_7	Sense of smell	6.000000e-06
GCST004735_8	Epstein-Barr virus copy number in lymphoblastoid cell lines	9.000000e-06
GCST007198_1	Parkinson’s disease (age at diagnosis)	9.000000e-09
GCST008156_82	Hip circumference adjusted for BMI	6.000000e-06
GCST010396_252	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-07
GCST010396_258	Gut microbiota (bacterial taxa, hurdle binary method)	2.000000e-07
GCST011742_54	Triglyceride levels in HIV infection	6.000000e-06

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004918	age at diagnosis
EFO:0008039	BMI-adjusted hip circumference
EFO:0007874	gut microbiome measurement
EFO:0004530	triglyceride measurement

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	decreases expression, increases expression	4
Tetrachlorodibenzodioxin	affects expression, decreases expression, increases expression	4
Cyclosporine	decreases expression	4
Valproic Acid	affects expression, increases expression	2
methylmercuric chloride	increases expression	1
methyleugenol	decreases expression	1
pirinixic acid	affects binding, decreases expression, increases activity	1
candoxin	decreases expression	1
Ampicillin	increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Quercetin	decreases expression	1
Silicon Dioxide	increases expression	1
Oxyquinoline	increases expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Aflatoxin B1	decreases expression	1
Zinc Sulfate	decreases expression	1
Copper Sulfate	decreases 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_C4CU	PRG-3/293T-Rex	Transformed cell line	Female

Clinical trials (associated diseases)

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