NAPEPLD
protein-codingN-acyl phosphatidylethanolamine phospholipase D, the group of Metallo-beta-lactamase fold containing family
Gene summary
NAPEPLD is a phospholipase D type enzyme that catalyzes the release of N-acylethanolamine (NAE) from N-acyl-phosphatidylethanolamine (NAPE) in the second step of the biosynthesis of N-acylethanolamine (Okamoto et al., 2004 [PubMed 14634025]).[supplied by OMIM, Oct 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~49.8 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 NAPEPLD variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001122838.3. 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 | 2 | 2 | ||||
| missense | 1 | 58 | 2 | 61 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 2 | 2 | ||||
| Total | 1 | 0 | 61 | 2 | 2 | 66 |
Highest pathogenic variant AF is 0.000006867585
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001116310.1 | 4 | MANE Select | |
| Ensembl | ENSP00000419188.1 | 4 | MANE Select | |
| RefSeq | NP_001373105.1 | 4 | Standard | |
| RefSeq | NP_001373106.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Retrograde endocannabinoid signaling - Homo sapiens (human)
- Cannabinoid receptor signaling
- Signaling by GPCR
- Disease
- Signal Transduction
Biological Process
- retinoid metabolic process
- temperature homeostasis
- aging
- phospholipid catabolic process
- response to isolation stress
Molecular Function
- zinc ion binding
- identical protein binding
- N-acylphosphatidylethanolamine-specific phospholipase D activity
- N-acetylphosphatidylethanolamine-hydrolysing phospholipas activity
Cellular Component
- Golgi membrane
- nuclear envelope
- nucleoplasm
- early endosome
- Golgi apparatus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000417955
- Coding exons
- 4
- Length
- 49785
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 42
- Defined
- 125746
- p
- 0.000167
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.312 | 203 | 216 | 0.940 | 0.0000114 | 2620 |
| Missense (PolyPhen) | 56 | 64.607 | 0.86677 | 735 | ||
| Synonymous | 0.359 | 72 | 76.0 | 0.948 | 0.00000426 | 722 |
| Loss of Function | 1.73 | 10 | 17.9 | 0.558 | 0.00000100 | 192 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00026 | 0.00026 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00022 | 0.00022 | rare |
| South Asian | 0.000098 | 0.000098 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Hydrolyzes N-acyl-phosphatidylethanolamines (NAPEs) to produce N-acylethanolamines (NAEs) and phosphatidic acid (PubMed:25684574, PubMed:14634025, PubMed:16527816). Responsible for the generation of these bioactive fatty acid ethanolamides (FAEs), including anandamide (N-arachidonoylethanolamine), the ligand of cannabinoid and vanilloid receptors (PubMed:14634025). As a regulator of lipid metabolism in the adipose tissue, mediates the crosstalk between adipocytes, gut microbiota and immune cells to control body temperature and weight. In particular, regulates energy homeostasis by promoting cold-induced brown or beige adipocyte differentiation program to generate heat from fatty acids and glucose (By similarity). {ECO:0000250|UniProtKB:Q8BH82, ECO:0000269|PubMed:14634025, ECO:0000269|PubMed:16527816, ECO:0000269|PubMed:25684574}.;
Recessive Scores
- pRec
- 0.185
Intolerance Scores
- LoFtool
- 0.474
- RVIS EVS
- 0
- RVIS percentile EVS
- 53.73
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.230
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |