PLA2G15
protein-codingphospholipase A2 group XV, the group of Phospholipases
Gene summary
Lysophospholipases are enzymes that act on biological membranes to regulate the multifunctional lysophospholipids. The protein encoded by this gene hydrolyzes lysophosphatidylcholine to glycerophosphorylcholine and a free fatty acid. This enzyme is present in the plasma and thought to be associated with high-density lipoprotein. A later paper contradicts the function of this gene. It demonstrates that this gene encodes a lysosomal enzyme instead of a lysophospholipase and has both calcium-independent phospholipase A2 and transacylase activities. [provided by RefSeq, Jul 2008]
- LYPLA3
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~15.8 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 PLA2G15 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_012320.4. 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 | 0 | |||||
| missense | 65 | 1 | 66 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 0 | 0 | 67 | 1 | 0 | 68 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_036452.1 | 6 | MANE Select | |
| Ensembl | ENSP00000219345.5 | 6 | MANE Select | |
| RefSeq | NP_001350480.1 | 6 | Standard | |
| Ensembl | ENSP00000394197.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Glycerophospholipid metabolism - Homo sapiens (human)
- Lysosome - Homo sapiens (human)
- Phospholipid Biosynthesis
- Metabolism of lipids
- Metabolism
Biological Process
- phospholipid metabolic process
- glycerophospholipid metabolic process
- ceramide metabolic process
- fatty acid catabolic process
- phosphatidylcholine catabolic process
Molecular Function
- lysophospholipase activity
- phospholipid binding
- O-acyltransferase activity
- calcium-independent phospholipase A2 activity
Cellular Component
- extracellular region
- extracellular space
- nucleoplasm
- lysosome
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000219345
- Coding exons
- 6
- Length
- 15755
- Individuals with no LoFs
- 125713
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 20
- Defined
- 125733
- p
- 0.0000795
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.751 | 226 | 260 | 0.869 | 0.0000161 | 2642 |
| Missense (PolyPhen) | 105 | 119.93 | 0.87549 | 1285 | ||
| Synonymous | 1.13 | 95 | 110 | 0.863 | 0.00000666 | 856 |
| Loss of Function | 3.04 | 4 | 17.9 | 0.224 | 8.47e-7 | 194 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.00012 | 0.000058 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00013 | 0.00013 | rare |
| South Asian | 0.000033 | 0.000033 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Has transacylase and calcium-independent phospholipase A2 activity (PubMed:20410020, PubMed:23958596). Catalyzes the formation of 1-O-acyl-N-acetylsphingosine and the concomitant release of a lyso-phospholipid (PubMed:11790796, PubMed:25727495). Has high activity with 1-palmitoyl-2-oleoyl-sn-glycero-3- phosphocholine (POPC) and 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), catalyzing the transfer of oleic acid to N-acetyl- sphingosine. Required for normal phospholipid degradation in alveolar and peritoneal macrophages and in spleen (By similarity). May have weak lysophospholipase activity (PubMed:10092508). {ECO:0000250|UniProtKB:Q8VEB4, ECO:0000269|PubMed:10092508, ECO:0000269|PubMed:11790796, ECO:0000269|PubMed:20410020, ECO:0000269|PubMed:23958596, ECO:0000269|PubMed:25727495}.;
Recessive Scores
- pRec
- 0.159
Intolerance Scores
- LoFtool
- 0.143
- RVIS EVS
- -0.34
- RVIS percentile EVS
- 30.56
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.993
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |