PLPPR4

Chr 1

phospholipid phosphatase related 4

Also known as: LPPR4, LPR4, PHP1, PRG-1, PRG1

NCBI Gene: 9890UniProt: Q7Z2D5

The protein encoded by this gene belongs to the lipid phosphate phosphatase (LPP) family. LPPs catalyze the dephosphorylation of a number of bioactive lipid mediators that regulate a variety of cell functions. This protein is specifically expressed in neurons. It is located in the membranes of outgrowing axons and has been shown to be important for axonal outgrowth during development and regenerative sprouting. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

0
Active trials
79
ClinVar variants
8
Pathogenic / LP
2.9
Missense Z
0.37
LOEUF
8
Pubs (2 yr)
Clinical Summary— PLPPR4
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
8 Pathogenic / Likely Pathogenic· 69 VUS of 79 total submissions
Some data sources returned errors (1)

ensembl: TimeoutError: The operation was aborted due to timeout

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.37LOEUF
pLI 0.861
Z-score 4.08
OE 0.18 (0.09–0.37)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.88Z-score
OE missense 0.61 (0.55–0.68)
266 obs / 435.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.18 (0.09–0.37)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.61 (0.55–0.68)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.00
0≤1.21.6
LoF obs/exp: 5 / 28.5Missense obs/exp: 266 / 435.0Syn Z: -0.03

ClinVar Variant Classifications

79 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic7
Likely Pathogenic1
VUS69
Likely Benign1
Benign1
7
Pathogenic
1
Likely Pathogenic
69
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
7
0
7
Likely Pathogenic
0
0
1
0
1
VUS
0
57
12
0
69
Likely Benign
0
0
0
1
1
Benign
0
0
0
1
1
Total05720279

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

PLPPR4 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Cell type-specific and subcellular expression of phospholipid phosphatase-related proteins to modulate lyso-phosphatidic acid synaptic signaling in the developing and adult CNS.
Polyzou A et al.·J Neurochem
2024
Prognostic value and molecular mechanism of photodynamic therapy and apoptosis related gene FGFR1 in bladder cancer.
Wang L et al.·Front Oncol
2025Functional
MiR-18a-LncRNA NONRATG-022419 pairs targeted PRG-1 regulates diabetic induced cognitive impairment by regulating NGF BDNF-Trkb signaling pathway.
Xiang Q et al.·Proteome Sci
2025
Neuroplasticity-Related Genes Correlate with Individual Differences in Distinct Phases of Oxycodone Self-Administration in Male Rats.
Vassoler FM et al.·Neuropharmacology
2024
Mechanism of Mongolian mind-body interactive therapy in regulating essential hypertension through HTR2B: A metabolome- and transcriptome-based study.
Fang J et al.·Heliyon
2024Functional
Dephosphorylation-related signature predicts the prognosis of papillary renal cell carcinoma.
Feng J et al.·Transl Cancer Res
2024
Pioglitazone mitigates high-fat diet-induced cardiac lipotoxicity and vulnerable arrhythmias by reducing excess lipid intermediates.
Yeh YH et al.·Biomed Pharmacother
2025
Top 7 full-text resultsSearch PubTator3 ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients