NAPEPLD

N-acyl phosphatidylethanolamine phospholipase D, the group of Metallo-beta-lactamase fold containing family

Basic information

Region (hg38): 7:103099775-103149560

Links

ENSG00000161048 ∙ NCBI:222236 ∙ OMIM:612334 ∙ HGNC:21683 ∙ Uniprot:Q6IQ20 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NAPEPLD gene.

• Inborn genetic diseases (16 variants)
• not provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NAPEPLD gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous					2	2
missense			16			16
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	16	0	2

Variants in NAPEPLD

This is a list of pathogenic ClinVar variants found in the NAPEPLD region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
7-103103443-C-T		not specified	Uncertain significance (Dec 28, 2022)
7-103103467-C-T		not specified	Uncertain significance (Aug 04, 2021)
7-103103494-C-G		not specified	Uncertain significance (Oct 06, 2021)
7-103115100-G-A		not specified	Uncertain significance (May 25, 2022)
7-103115123-G-C		not specified	Uncertain significance (Sep 27, 2022)
7-103115174-C-G		not specified	Uncertain significance (Mar 01, 2023)
7-103119619-G-C		not specified	Uncertain significance (Jul 09, 2021)
7-103119622-C-G		not specified	Uncertain significance (Dec 07, 2021)
7-103119674-C-T		not specified	Uncertain significance (Jan 12, 2024)
7-103119704-C-T		not specified	Uncertain significance (Feb 22, 2023)
7-103119720-T-C			Benign (May 09, 2018)
7-103119754-C-A		not specified	Uncertain significance (Jan 02, 2024)
7-103119815-C-T		not specified	Uncertain significance (Dec 16, 2021)
7-103119863-T-C		not specified	Uncertain significance (Dec 11, 2023)
7-103119880-A-G		not specified	Uncertain significance (Apr 24, 2023)
7-103119937-T-C		not specified	Uncertain significance (Oct 02, 2023)
7-103119955-T-C		not specified	Uncertain significance (Nov 27, 2023)
7-103120104-T-G		not specified	Uncertain significance (Nov 23, 2021)
7-103120111-A-G		not specified	Uncertain significance (Jan 25, 2023)
7-103120117-G-A		not specified	Uncertain significance (May 25, 2022)
7-103120152-T-G		not specified	Uncertain significance (Nov 30, 2022)
7-103120175-G-A		not specified	Uncertain significance (Oct 10, 2023)
7-103128493-C-G		not specified	Uncertain significance (Dec 08, 2023)
7-103128574-G-A		not specified	Uncertain significance (Dec 27, 2023)
7-103128629-G-A			Benign (May 09, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NAPEPLD	protein_coding	protein_coding	ENST00000417955	4	49785

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000294	0.939	125704	0	42	125746	0.000167

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.312	203	216	0.940	0.0000114	2620
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000264	0.000264
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.00	0.00
European (Non-Finnish)	0.000221	0.000220
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000980	0.0000980
Other	0.000655	0.000652

dbNSFP

Source: dbNSFP

• 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}.
• Pathway: Retrograde endocannabinoid signaling - Homo sapiens (human);Cannabinoid receptor signaling;Signaling by GPCR;Disease;Signal Transduction;The canonical retinoid cycle in rods (twilight vision);Biosynthesis of A2E, implicated in retinal degradation;G alpha (i) signalling events;Retinoid cycle disease events;Diseases associated with visual transduction;Visual phototransduction;GPCR downstream signalling;Diseases of signal transduction (Consensus)

Recessive Scores

• pRec: 0.185

Intolerance Scores

• loftool: 0.474
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.157
• hipred: N
• hipred_score: 0.378
• ghis: 0.582

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.230

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Napepld
• Phenotype: homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: retinoid metabolic process;temperature homeostasis;aging;phospholipid catabolic process;response to isolation stress;host-mediated regulation of intestinal microbiota composition;positive regulation of inflammatory response;N-acylethanolamine metabolic process;N-acylphosphatidylethanolamine metabolic process;positive regulation of brown fat cell differentiation;negative regulation of eating behavior
• Cellular component: Golgi membrane;nuclear envelope;nucleoplasm;early endosome;Golgi apparatus;cytosol;early endosome membrane;photoreceptor outer segment membrane;membrane-bounded organelle;extracellular exosome
• Molecular function: zinc ion binding;identical protein binding;N-acylphosphatidylethanolamine-specific phospholipase D activity;N-acetylphosphatidylethanolamine-hydrolysing phospholipas activity