PLPP7

Summary

PLPP7 (phospholipid phosphatase 7 (inactive), HGNC:28174) is a protein-coding gene on chromosome 9q34.13, encoding Inactive phospholipid phosphatase 7 (Q8NBV4). Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling.

Predicted to enable sphingosine-1-phosphate phosphatase activity. Predicted to act upstream of or within negative regulation of myotube differentiation. Predicted to be located in endoplasmic reticulum membrane and nucleus. Predicted to be active in membrane and nuclear envelope.

Source: NCBI Gene 84814 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 71 total
• MANE Select transcript: NM_032728

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28174
Approved symbol	PLPP7
Name	phospholipid phosphatase 7 (inactive)
Location	9q34.13
Locus type	gene with protein product
Status	Approved
Aliases	MGC12921, FLJ14662, NET39
Ensembl gene	ENSG00000160539
Ensembl biotype	protein_coding
OMIM	618743
Entrez	84814

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 nonsense_mediated_decay

ENST00000372261, ENST00000372264, ENST00000645295, ENST00000912088, ENST00000968390

RefSeq mRNA: 2 — MANE Select: NM_032728 NM_001411021, NM_032728

CCDS: CCDS6942, CCDS94515

Canonical transcript exons

ENST00000372264 — 2 exons

Exon	Start	End
ENSE00001457377	131307923	131309261
ENSE00001457379	131289723	131290448

Expression profiles

Bgee: expression breadth ubiquitous, 195 present calls, max score 97.42.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.4331 / max 156.2492, expressed in 1040 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99091	3.7662	1031
99093	0.5446	79
99092	0.0622	22
99094	0.0601	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	97.42	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.07	gold quality
gastrocnemius	UBERON:0001388	96.74	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.65	gold quality
tibialis anterior	UBERON:0001385	96.58	silver quality
left ventricle myocardium	UBERON:0006566	96.12	gold quality
quadriceps femoris	UBERON:0001377	95.89	gold quality
muscle of leg	UBERON:0001383	95.73	gold quality
vastus lateralis	UBERON:0001379	95.66	gold quality
skeletal muscle tissue	UBERON:0001134	95.46	gold quality
right atrium auricular region	UBERON:0006631	95.21	gold quality
heart left ventricle	UBERON:0002084	95.13	gold quality
cardiac atrium	UBERON:0002081	95.08	gold quality
cardiac ventricle	UBERON:0002082	94.93	gold quality
myocardium	UBERON:0002349	94.72	gold quality
deltoid	UBERON:0001476	94.66	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	93.85	gold quality
biceps brachii	UBERON:0001507	93.84	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	93.31	gold quality
muscle tissue	UBERON:0002385	92.61	gold quality
heart	UBERON:0000948	92.51	gold quality
heart right ventricle	UBERON:0002080	92.12	gold quality
body of tongue	UBERON:0011876	85.01	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.74	gold quality
right frontal lobe	UBERON:0002810	83.57	gold quality
Brodmann (1909) area 9	UBERON:0013540	83.08	gold quality
cerebellar hemisphere	UBERON:0002245	82.97	gold quality
cerebellar cortex	UBERON:0002129	82.93	gold quality
cerebellum	UBERON:0002037	82.29	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	82.19	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	365.61
E-ANND-3	no	2.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

31 targeting PLPP7, 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-4692	100.00	67.32	2066
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-370-5P	99.78	66.81	706
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-18A-3P	99.56	65.68	1092
HSA-MIR-6751-5P	99.56	64.99	1145
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-6803-5P	99.19	63.90	1026
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-4709-5P	98.51	67.25	1335
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-890	97.47	68.67	982
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
HSA-MIR-1237-5P	95.38	62.21	451
HSA-MIR-4488	95.38	62.00	443
HSA-MIR-4697-5P	95.38	61.72	457
HSA-MIR-7109-3P	94.23	67.19	743
HSA-MIR-4445-3P	93.28	66.18	106
HSA-MIR-548AL	93.28	65.60	109

Literature-anchored findings (GeneRIF, showing 2)

• NET39 is a muscle-enriched nuclear envelope transmembrane protein, which regulates initiation of myogenic differentiation via affecting mTOR-IGF-II pathway. (PMID:19704009)
• The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization. (PMID:33514739)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	plpp7a	ENSDARG00000103712
danio_rerio	PLPP7	ENSDARG00000109568
mus_musculus	Plpp7	ENSMUSG00000051373
rattus_norvegicus	Plpp7	ENSRNOG00000010068
drosophila_melanogaster	CG31717	FBGN0051717
caenorhabditis_elegans		WBGENE00020486

Paralogs (3): SGPP1 (ENSG00000126821), SGPP2 (ENSG00000163082), PLPP6 (ENSG00000205808)

Protein

Protein identifiers

Inactive phospholipid phosphatase 7 — Q8NBV4 (reviewed: Q8NBV4)

Alternative names: Phosphatidic acid phosphatase type 2 domain-containing protein 3

All UniProt accessions (4): Q8NBV4, A0A2R8Y4I9, A0A384NPM3, X6R886

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role as negative regulator of myoblast differentiation, in part through effects on MTOR signaling. Has no detectable enzymatic activity.

Subunit / interactions. Homo and heterooligomer. Interacts with MTOR; controls MTOR-dependent IGF2 expression during myoblast differentiation.

Subcellular location. Nucleus envelope. Endoplasmic reticulum membrane. Membrane.

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

RefSeq proteins (2): NP_001397950, NP_116117* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000326	PAP2/HPO	Domain
IPR036938	PAP2/HPO_sf	Homologous_superfamily

Pfam: PF01569

UniProt features (17 total): topological domain 5, transmembrane region 4, region of interest 2, modified residue 2, sequence variant 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NBV4-F1	80.10	0.60

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): 43, 62

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 68 (showing top): GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, GCANCTGNY_MYOD_Q6, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_MYOTUBE_DIFFERENTIATION, CAGCTG_AP4_Q5, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, GOBP_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, OCT1_03, HEN1_01, HP1SITEFACTOR_Q6, GOBP_REGULATION_OF_MYOTUBE_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS, GOBP_MYOTUBE_DIFFERENTIATION

GO Biological Process (1): negative regulation of myotube differentiation (GO:0010832)

GO Molecular Function (1): sphingosine-1-phosphate phosphatase activity (GO:0042392)

GO Cellular Component (5): nuclear envelope (GO:0005635), endoplasmic reticulum membrane (GO:0005789), membrane (GO:0016020), nucleus (GO:0005634), endoplasmic reticulum (GO:0005783)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
endomembrane system	2
intracellular membrane-bounded organelle	2
regulation of myotube differentiation	1
myotube differentiation	1
negative regulation of striated muscle cell differentiation	1
lipid phosphatase activity	1
nucleus	1
organelle envelope	1
organelle membrane	1
nuclear outer membrane-endoplasmic reticulum membrane network	1
endoplasmic reticulum subcompartment	1
cellular anatomical structure	1
cytoplasm	1

Protein interactions and networks

STRING

478 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PLPP7	TMEM38A	Q9H6F2	707
PLPP7	TMEM120A	Q9BXJ8	642
PLPP7	EMD	P50402	578
PLPP7	LEMD2	Q8NC56	572
PLPP7	PLPP4	Q5VZY2	541
PLPP7	MYORG	Q6NSJ0	533
PLPP7	TMEM201	Q5SNT2	525
PLPP7	PLPP5	Q8NEB5	515
PLPP7	OSBPL2	Q9H1P3	509
PLPP7	DEGS2	Q6QHC5	497
PLPP7	LEMD3	Q9Y2U8	484
PLPP7	TMEM214	Q6NUQ4	480
PLPP7	TM7SF2	O76062	476
PLPP7	WFS1	O76024	475
PLPP7	TMEM209	Q96SK2	453

IntAct

2 interactions, top by confidence:

A	B	Type	Score
PLPP7	SMO	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (1): PPAPDC3 (Two-hybrid)

ESM2 similar proteins: A1L272, A2RV80, A4IF30, A6QL92, A6QPI1, O02777, O80605, P17200, P20272, P21554, P47746, P51810, P56971, P70259, Q1LZI2, Q2V4F9, Q3TDN0, Q3UGM2, Q4R794, Q5F383, Q5FVJ3, Q5IS73, Q5R4D7, Q5R6J3, Q5RD30, Q66H88, Q6P0E8, Q6P499, Q6R5J2, Q71SP5, Q8BGN5, Q8BZK4, Q8CBH5, Q8IY50, Q8NA31, Q8NBV4, Q8R314, Q8RWF4, Q8WV83, Q91WB2

Diamond homologs: O34349, Q58DI5, Q5TZ07, Q66H88, Q6P0E8, Q8IY26, Q8NBV4, Q9D4F2, B2RLI7, P9WI52, P9WI53, Q1MA49, Q2K2U9, Q57819, Q5FVJ3, Q91WB2, P80143, Q9SUW4

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

440 predictions. Top by Δscore:

Variant	Effect	Δscore
9:131290447:GG:G	donor_gain	1.0000
9:131290448:GG:G	donor_gain	1.0000
9:131292956:G:GT	donor_gain	1.0000
9:131307918:A:AG	acceptor_gain	1.0000
9:131307919:ACAG:A	acceptor_loss	1.0000
9:131307921:A:AC	acceptor_loss	1.0000
9:131307921:A:AG	acceptor_gain	1.0000
9:131307922:G:GA	acceptor_gain	1.0000
9:131307922:GC:G	acceptor_gain	1.0000
9:131307922:GCCC:G	acceptor_gain	1.0000
9:131307922:GCCCT:G	acceptor_gain	1.0000
9:131290424:G:GT	donor_gain	0.9900
9:131290449:G:A	donor_loss	0.9900
9:131290449:G:GG	donor_gain	0.9900
9:131290450:TGAG:T	donor_loss	0.9900
9:131290451:G:GC	donor_loss	0.9900
9:131292962:A:AG	donor_gain	0.9900
9:131307920:C:G	acceptor_gain	0.9900
9:131307922:GCC:G	acceptor_gain	0.9900
9:131307919:A:G	acceptor_gain	0.9800
9:131290452:A:AC	donor_loss	0.9700
9:131290446:TGG:T	donor_gain	0.9600
9:131290447:GGG:G	donor_gain	0.9600
9:131292855:A:G	donor_gain	0.9600
9:131290445:CTGG:C	donor_gain	0.9500
9:131292956:GAA:G	donor_gain	0.9500
9:131290398:TG:T	donor_gain	0.9400
9:131290428:TGCTC:T	donor_gain	0.9400
9:131290444:CCTGG:C	donor_gain	0.9400
9:131291242:G:GT	donor_gain	0.9400

AlphaMissense

1742 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:131290239:C:A	A81D	1.000
9:131290275:C:T	S93F	1.000
9:131290370:T:A	W125R	1.000
9:131290370:T:C	W125R	1.000
9:131290440:T:C	L148P	1.000
9:131308132:T:A	W221R	1.000
9:131308132:T:C	W221R	1.000
9:131308211:G:A	G247D	1.000
9:131290256:G:C	A87P	0.999
9:131290262:G:C	D89H	0.999
9:131290262:G:T	D89Y	0.999
9:131290263:A:C	D89A	0.999
9:131290263:A:T	D89V	0.999
9:131290274:T:C	S93P	0.999
9:131290275:C:A	S93Y	0.999
9:131290353:C:A	T119K	0.999
9:131290356:G:A	G120D	0.999
9:131290379:G:C	G128R	0.999
9:131290380:G:A	G128D	0.999
9:131290391:T:C	C132R	0.999
9:131290395:T:C	L133P	0.999
9:131290438:T:A	N147K	0.999
9:131290438:T:G	N147K	0.999
9:131307926:T:C	L152P	0.999
9:131307934:G:C	D155H	0.999
9:131308040:C:A	P190Q	0.999
9:131308054:A:C	S195R	0.999
9:131308056:C:A	S195R	0.999
9:131308056:C:G	S195R	0.999
9:131308058:G:C	R196P	0.999

dbSNP variants (sampled 300 via entrez): RS1000035008 (9:131305919 G>A,T), RS1000086827 (9:131306186 G>A), RS1000437345 (9:131295992 T>C), RS1000529509 (9:131301763 C>T), RS1000542952 (9:131306164 G>A), RS1000583298 (9:131302099 G>A), RS1000686786 (9:131300559 G>A,C), RS1000737514 (9:131296913 G>A,C), RS1000806908 (9:131295772 T>C), RS1000846446 (9:131291301 A>ACATG), RS1001085160 (9:131304924 C>G,T), RS1001223555 (9:131293125 A>G), RS1001642155 (9:131305849 G>A), RS1001777465 (9:131300241 C>T), RS1001961621 (9:131290021 C>G)

Disease associations

OMIM: gene MIM:618743 | disease phenotypes: MIM:236670, MIM:609308, MIM:613155

GenCC curated gene-disease

Mondo (3): muscular dystrophy-dystroglycanopathy, type A (MONDO:0000171), autosomal recessive limb-girdle muscular dystrophy type 2K (MONDO:0012248), muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1 (MONDO:0013159)

Orphanet (2): POMT1-related limb-girdle muscular dystrophy R11 (Orphanet:86812), Walker-Warburg syndrome (Orphanet:899)

HPO phenotypes

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

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST010320_136	PR interval	5.000000e-12
GCST010321_18	PR interval	6.000000e-13
GCST010796_894	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_895	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-11
GCST010796_896	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-12
GCST010796_897	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-09
GCST010796_898	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-12

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058494	Walker-Warburg Syndrome	C10.500.507.450.499.249.500; C11.270.881; C16.131.666.507.450.499.249.500; C16.320.577.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases methylation, affects cotreatment, decreases expression	5
Cadmium	decreases reaction, increases abundance, increases palmitoylation, decreases expression	2
aristolochic acid I	increases expression	1
FR900359	increases phosphorylation	1
propionaldehyde	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
butyraldehyde	decreases expression	1
2-bromopalmitate	decreases reaction, increases abundance, increases palmitoylation	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
dorsomorphin	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Caffeine	decreases phosphorylation	1
Diethylhexyl Phthalate	decreases expression	1
Endosulfan	decreases expression	1
Silicon Dioxide	decreases expression	1
Triclosan	decreases expression	1
1-Methyl-4-phenylpyridinium	increases expression	1
Cadmium Chloride	decreases reaction, increases abundance, increases palmitoylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04001595	Not specified	UNKNOWN	Global FKRP Registry
NCT05989620	Not specified	RECRUITING	Long-Term Development of Muscular Dystrophy Outcome Assessments