PLPPR4
protein-codingphospholipid phosphatase related 4, the group of Phospholipid phosphatase related
Gene summary
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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~45.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PLPPR4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014839.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 2 | |||
| missense | 60 | 60 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 62 | 1 | 1 | 64 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055654.3 | 7 | MANE Select | |
| Ensembl | ENSP00000359204.4 | 7 | MANE Select | |
| RefSeq | NP_001159724.2 | 6 | Standard | |
| Ensembl | ENSP00000394913.2 | 6 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Signaling by GPCR
- Signal Transduction
- Lysosphingolipid and LPA receptors
- Class A/1 (Rhodopsin-like receptors)
- GPCR ligand binding
Biological Process
- phospholipid metabolic process
- axonogenesis
- phospholipid dephosphorylation
- inner ear development
Molecular Function
- phosphatidate phosphatase activity
- phosphatase activity
- lipid phosphatase activity
Cellular Component
- plasma membrane
- integral component of plasma membrane
- glutamatergic synapse
- integral component of postsynaptic density membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370185
- Coding exons
- 7
- Length
- 45638
- Individuals with no LoFs
- 125613
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 7
- Defined
- 125620
- p
- 0.0000279
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.88 | 266 | 435 | 0.612 | 0.0000232 | 4977 |
| Missense (PolyPhen) | 64 | 159.62 | 0.40095 | 1810 | ||
| Synonymous | -0.0328 | 167 | 166 | 1.00 | 0.00000905 | 1541 |
| Loss of Function | 4.08 | 5 | 28.5 | 0.176 | 0.00000178 | 323 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00018 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000036 | 0.000035 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes lysophosphatidic acid (LPA). Facilitates axonal outgrowth during development and regenerative sprouting. In the outgrowing axons acts as an ecto-enzyme and attenuates phospholipid-induced axon collapse in neurons and facilitates outgrowth in the hippocampus. {ECO:0000269|PubMed:12730698}.;
Intolerance Scores
- RVIS EVS
- -0.38
- RVIS percentile EVS
- 27.69
Essentials
- Essential (gene trap)
- N