NAAA

protein-coding

N-acylethanolamine acid amidase

Gene summary

Enables DNA-binding transcription factor binding activity and hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides. Involved in several processes, including N-acylethanolamine metabolic process; N-acylphosphatidylethanolamine metabolic process; and sphingosine metabolic process. Located in lysosome and membrane. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

ASAHL

MANE transcript

NM_014435.4

Inheritance

—

ClinVar variants

U:57B:11

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.82

Max pathogenic AF

—

Genomic locus

chr4:75,910,655-75,941,013

External References & Databases

Ensembl (ENSG00000138744)

Transcript & Mutation Effects

hg38 • Region Span ~30.4 kb

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GenCC 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 NAAA variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 54

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_014435.4. 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			4 clinvar	3 clinvar	1 clinvar	8
missense			51 clinvar	7 clinvar		58
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	57	10	1	68

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 48 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_014435.4	RefSeq	NP_055250.2	10	MANE Select
ENST00000286733.9	Ensembl	ENSP00000286733.4	10	MANE Select
NM_001042402.2	RefSeq	NP_001035861.1	9	Standard
NM_001363719.2	RefSeq	NP_001350648.1	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Neuronal System
Neurotransmitter release cycle
Transmission across Chemical Synapses

Biological Process

lipid metabolic process
neurotransmitter secretion
biological_process

Molecular Function

transcription factor binding
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds

Cellular Component

cytoplasm
lysosomal lumen
extracellular exosome
presynapse

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000286733
Coding exons: 10
Length: 30396
Individuals with no LoFs: 124034
Homozygous LoFs: 10
Heterozygous LoFs: 751
Defined: 124795
p: 0.00305

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.825	174	207	0.839	0.0000112	2290
Missense (PolyPhen)		54	65.484	0.82463		719
Synonymous	1.14	73	86.5	0.843	0.00000482	734
Loss of Function	0.754	17	20.7	0.821	0.00000107	221

Population LoF Frequency

Population	CAF	p-value	Status
African	0.040	0.040	notable
Latino/Admixed American	0.0027	0.0027	notable
Ashkenazi Jewish	0.000099	0.000099	rare
East Asian	0.00028	0.00028	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00031	0.00031	rare
South Asian	0.00043	0.00042	rare
Other	0.0010	0.00099	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Degrades bioactive fatty acid amides to their corresponding acids, with the following preference: N- palmitoylethanolamine > N-myristoylethanolamine > N- lauroylethanolamine = N-stearoylethanolamine > N- arachidonoylethanolamine > N-oleoylethanolamine. Also exhibits weak hydrolytic activity against the ceramides N- lauroylsphingosine and N-palmitoylsphingosine. {ECO:0000269|PubMed:15655246}.;

Recessive Scores

pRec: 0.219

Intolerance Scores

LoFtool: 0.851
RVIS EVS: 1.75
RVIS percentile EVS: 96.67

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.0352

Gene Damage Prediction

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