PLPPR5

Summary

PLPPR5 (phospholipid phosphatase related 5, HGNC:31703) is a protein-coding gene on chromosome 1p21.3, encoding Phospholipid phosphatase-related protein type 5 (Q32ZL2). Induces filopodia formation and promotes neurite growth in a CDC42-independent manner; impedes neurite growth inhibitory-mediated axonal retraction.

The protein encoded by this gene is a type 2 member of the phosphatidic acid phosphatase (PAP) family. All type 2 members of this protein family contain 6 transmembrane regions, and a consensus N-glycosylation site. PAPs convert phosphatidic acid to diacylglycerol, and function in de novo synthesis of glycerolipids as well as in receptor-activated signal transduction mediated by phospholipase D. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Source: NCBI Gene 163404 — RefSeq curated summary.

At a glance

• GWAS associations: 11
• Clinical variants (ClinVar): 33 total
• MANE Select transcript: NM_001037317

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:31703
Approved symbol	PLPPR5
Name	phospholipid phosphatase related 5
Location	1p21.3
Locus type	gene with protein product
Status	Approved
Aliases	PAP2D, PAP2, LPPR5, PRG5
Ensembl gene	ENSG00000117598
Ensembl biotype	protein_coding
OMIM	617287
Entrez	163404

Gene structure

Transcript identifiers

Ensembl transcripts: 7 — 6 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000263177, ENST00000370188, ENST00000534652, ENST00000672681, ENST00000696571, ENST00000904845, ENST00000951067

RefSeq mRNA: 2 — MANE Select: NM_001037317 NM_001010861, NM_001037317

CCDS: CCDS30778, CCDS30779

Canonical transcript exons

ENST00000263177 — 6 exons

Exon	Start	End
ENSE00000777602	98921882	98922058
ENSE00000831240	98953070	98953320
ENSE00000831241	98956609	98956741
ENSE00001421078	99004435	99004861
ENSE00001452026	98914786	98914920
ENSE00001875959	98890245	98893104

Expression profiles

Bgee: expression breadth broad, 96 present calls, max score 94.72.

FANTOM5 (CAGE): breadth broad, TPM avg 1.0760 / max 138.8315, expressed in 234 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
13480	0.6448	188
13481	0.3203	122
13482	0.1110	52

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	94.72	gold quality
endothelial cell	CL:0000115	92.87	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.89	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.31	gold quality
primary visual cortex	UBERON:0002436	82.20	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.49	gold quality
prefrontal cortex	UBERON:0000451	80.85	gold quality
occipital lobe	UBERON:0002021	80.45	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.81	gold quality
entorhinal cortex	UBERON:0002728	79.49	gold quality
cerebral cortex	UBERON:0000956	78.72	gold quality
ganglionic eminence	UBERON:0004023	78.66	gold quality
neocortex	UBERON:0001950	78.54	gold quality
anterior cingulate cortex	UBERON:0009835	78.42	gold quality
frontal cortex	UBERON:0001870	78.14	gold quality
frontal lobe	UBERON:0016525	78.14	gold quality
temporal lobe	UBERON:0001871	77.76	gold quality
superior frontal gyrus	UBERON:0002661	77.58	gold quality
middle temporal gyrus	UBERON:0002771	77.44	gold quality
Brodmann (1909) area 9	UBERON:0013540	77.33	gold quality
amygdala	UBERON:0001876	77.18	gold quality
Ammon’s horn	UBERON:0001954	77.06	gold quality
nucleus accumbens	UBERON:0001882	75.92	gold quality
right frontal lobe	UBERON:0002810	74.13	gold quality
postcentral gyrus	UBERON:0002581	74.12	gold quality
parietal lobe	UBERON:0001872	73.82	gold quality
hypothalamus	UBERON:0001898	73.48	gold quality
forebrain	UBERON:0001890	73.26	gold quality
caudate nucleus	UBERON:0001873	72.82	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	70.65	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.26

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

176 targeting PLPPR5, 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-4682	100.00	68.89	1258
HSA-MIR-1193	100.00	65.93	529
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-432-3P	100.00	67.86	705
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-511-3P	99.99	68.85	1467
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-559	99.95	72.28	3609
HSA-MIR-6755-5P	99.95	65.59	464
HSA-MIR-548AB	99.95	71.31	3488
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505

Literature-anchored findings (GeneRIF, showing 1)

• A novel human phosphatidic acid phosphatase type 2 isoform cDNAs (PAP2d) from the fetal brain cDNA library was cloned and characterized. (PMID:16010976)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	plppr5a	ENSDARG00000057209
danio_rerio	plppr5b	ENSDARG00000101348
mus_musculus	Plppr5	ENSMUSG00000033342
rattus_norvegicus	Plppr5	ENSRNOG00000016878
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), PLPPR4 (ENSG00000117600), PLPPR3 (ENSG00000129951), PLPP2 (ENSG00000141934), PLPP5 (ENSG00000147535), PLPPR1 (ENSG00000148123), PLPP3 (ENSG00000162407), PLPP4 (ENSG00000203805)

Protein

Protein identifiers

Phospholipid phosphatase-related protein type 5 — Q32ZL2 (reviewed: Q32ZL2)

Alternative names: Lipid phosphate phosphatase-related protein type 5, Phosphatidic acid phosphatase type 2d, Plasticity-related gene 5 protein

All UniProt accessions (3): Q32ZL2, A0A5F9ZI76, A0A8Q3SIM6

UniProt curated annotations — full annotation on UniProt →

Function. Induces filopodia formation and promotes neurite growth in a CDC42-independent manner; impedes neurite growth inhibitory-mediated axonal retraction.

Subcellular location. Cell membrane.

Tissue specificity. Isoform 1 is expressed in brain, lung, kidney and colon. Isoform 2 is expressed in placenta, skeletal muscle and kidney.

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

Isoforms (2)

UniProt ID	Names	Canonical?
Q32ZL2-1	1, PAP2d_v1	yes
Q32ZL2-2	2, PAP2d_v2

RefSeq proteins (2): NP_001010861, NP_001032394* (*=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 (8 total): transmembrane region 6, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q32ZL2-F1	82.11	0.55

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-419408	Lysosphingolipid and LPA receptors

MSigDB gene sets: 97 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_LIPID_MODIFICATION, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_PHOSPHOLIPID_DEPHOSPHORYLATION, GOBP_NEUROGENESIS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, GOBP_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, ATGTTAA_MIR302C, GOBP_POSITIVE_REGULATION_OF_CELLULAR_COMPONENT_BIOGENESIS, GOBP_REGULATION_OF_CELL_PROJECTION_ORGANIZATION, GOBP_POSITIVE_REGULATION_OF_FILOPODIUM_ASSEMBLY, GOBP_LIPID_METABOLIC_PROCESS, GOBP_REGULATION_OF_NEURON_PROJECTION_DEVELOPMENT, GOBP_DEPHOSPHORYLATION, GOBP_CELL_PROJECTION_ORGANIZATION

GO Biological Process (5): phospholipid metabolic process (GO:0006644), signal transduction (GO:0007165), positive regulation of neuron projection development (GO:0010976), phospholipid dephosphorylation (GO:0046839), positive regulation of filopodium assembly (GO:0051491)

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
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
dephosphorylation	1
lipid modification	1
filopodium assembly	1
regulation of filopodium assembly	1
positive regulation of plasma membrane bounded cell projection assembly	1
lipid phosphatase activity	1
membrane	1
cell periphery	1
cellular anatomical structure	1

Protein interactions and networks

STRING

796 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPPR5	SNX7	Q9UNH6	545
PLPPR5	PALMD	Q9NP74	447
PLPPR5	EPHX2	P34913	399
PLPPR5	TMEM25	Q86YD3	370
PLPPR5	LYPD3	O95274	366
PLPPR5	WFDC8	Q8IUA0	365
PLPPR5	CDK15	Q96Q40	354
PLPPR5	PRRG3	Q9BZD7	345
PLPPR5	CHCHD7	Q9BUK0	342
PLPPR5	FAM53B	Q14153	334
PLPPR5	CD53	P19397	333
PLPPR5	CXorf38	Q8TB03	331
PLPPR5	HSDL1	Q3SXM5	326
PLPPR5	IP6K2	Q9UHH9	323
PLPPR5	VMAC	Q2NL98	316

IntAct

2 interactions, top by confidence:

A	B	Type	Score
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350

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, Q86AF0, Q8K593, Q8LFD1, Q8NEB5, Q99JY8, Q9DAX2

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	32
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1232 predictions. Top by Δscore:

Variant	Effect	Δscore
1:98893105:C:CC	acceptor_gain	1.0000
1:98918665:T:TA	donor_gain	1.0000
1:98953068:A:AC	donor_gain	1.0000
1:98953069:C:CC	donor_gain	1.0000
1:98953069:CGG:C	donor_gain	1.0000
1:98953069:CGGT:C	donor_gain	1.0000
1:98953083:G:C	donor_gain	1.0000
1:98954785:G:C	donor_gain	1.0000
1:98956607:A:AC	donor_gain	1.0000
1:98956608:C:CC	donor_gain	1.0000
1:98956742:C:CC	acceptor_gain	1.0000
1:98956743:T:C	acceptor_gain	1.0000
1:98956743:T:TC	acceptor_gain	1.0000
1:99004429:GCTT:G	donor_loss	1.0000
1:99004430:CTTAC:C	donor_loss	1.0000
1:99004431:TTA:T	donor_loss	1.0000
1:99004432:TACCA:T	donor_loss	1.0000
1:99004433:A:AC	donor_gain	1.0000
1:99004434:C:CC	donor_gain	1.0000
1:99004434:C:G	donor_loss	1.0000
1:99004434:CCA:C	donor_gain	1.0000
1:98893100:TGGTT:T	acceptor_gain	0.9900
1:98893101:GGTT:G	acceptor_gain	0.9900
1:98893102:GTT:G	acceptor_gain	0.9900
1:98893102:GTTCT:G	acceptor_loss	0.9900
1:98893103:TT:T	acceptor_gain	0.9900
1:98893103:TTCT:T	acceptor_loss	0.9900
1:98893104:TCTG:T	acceptor_loss	0.9900
1:98893105:C:T	acceptor_loss	0.9900
1:98893106:T:G	acceptor_loss	0.9900

AlphaMissense

2094 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:98921904:C:T	G259E	0.999
1:98921905:C:G	G259R	0.999
1:98921905:C:T	G259R	0.999
1:98921916:C:T	G255D	0.999
1:98921917:C:G	G255R	0.999
1:98921943:C:G	R246P	0.999
1:98953094:A:C	S199R	0.999
1:98953094:A:T	S199R	0.999
1:98953096:T:G	S199R	0.999
1:98953116:G:T	P192Q	0.999
1:98953118:A:C	F191L	0.999
1:98953118:A:T	F191L	0.999
1:98953120:A:G	F191L	0.999
1:98953128:C:G	R188P	0.999
1:98953160:A:C	C177W	0.999
1:98953161:C:G	C177S	0.999
1:98953161:C:T	C177Y	0.999
1:98953162:A:T	C177S	0.999
1:98953226:A:C	C155W	0.999
1:98953227:C:G	C155S	0.999
1:98953227:C:T	C155Y	0.999
1:98953228:A:G	C155R	0.999
1:98953228:A:T	C155S	0.999
1:98953238:G:C	F151L	0.999
1:98953238:G:T	F151L	0.999
1:98953239:A:C	F151C	0.999
1:98953239:A:G	F151S	0.999
1:98953240:A:G	F151L	0.999
1:98953257:C:A	G145V	0.999
1:98953257:C:T	G145E	0.999

dbSNP variants (sampled 300 via entrez): RS1000057987 (1:98990185 A>G), RS1000065571 (1:98983889 T>C), RS1000084363 (1:98898740 G>C), RS1000129181 (1:98916034 A>G), RS1000178274 (1:98995641 C>A), RS1000196208 (1:99000775 T>C), RS1000235908 (1:98946703 T>C), RS1000242941 (1:98904866 G>A,T), RS1000293164 (1:98995911 C>A), RS1000332661 (1:98953388 TGTGTGTGA>T), RS1000373260 (1:98982156 C>A,T), RS1000398700 (1:98940650 G>A), RS1000421159 (1:99002681 T>C), RS1000452163 (1:99002969 C>A,T), RS1000458436 (1:98946879 A>T)

Disease associations

OMIM: gene MIM:617287 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

11 associations (top):

Study	Trait	p-value
GCST001713_30	Dental caries	1.000000e-06
GCST001762_269	Obesity-related traits	5.000000e-07
GCST001762_88	Obesity-related traits	9.000000e-06
GCST001786_10	Dental caries	2.000000e-06
GCST002471_1	Blood pressure (anthropometric measures interaction)	2.000000e-06
GCST003469_3	Response to cognitive-behavioural therapy in anxiety disorder	9.000000e-06
GCST003542_177	Night sleep phenotypes	8.000000e-07
GCST004705_1	Blood pressure	3.000000e-06
GCST007327_28	Smoking status (ever vs never smokers)	3.000000e-08
GCST008359_4	Response to cognitive-behavioural therapy in anxiety disorder	2.000000e-06
GCST008667_12	Smoking status (heavy vs never)	3.000000e-08

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0003940	physical activity
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0006336	diastolic blood pressure
EFO:0007820	cognitive behavioural therapy
EFO:0006335	systolic blood pressure
EFO:0004318	smoking behavior
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

22 total (human), top 22 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	increases expression, affects cotreatment	2
aristolochic acid I	decreases expression	1
propionaldehyde	increases methylation	1
bisphenol A	affects cotreatment, increases methylation	1
nonanal	increases methylation	1
n-hexanal	increases methylation	1
arsenite	affects binding, increases reaction	1
butyraldehyde	increases methylation	1
caprylic aldehyde	increases methylation	1
beta-methylcholine	affects expression	1
pentanal	increases methylation	1
heptanal	increases methylation	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
NSC 689534	affects binding, decreases expression	1
Arsenic Trioxide	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Atrazine	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carbamazepine	affects expression	1
Copper	affects binding, decreases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SV79	HAP1 LPPR5 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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