NAAA Gene

Name	N-acylethanolamine acid amidase
Description	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, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nN‐acylethanolamine acid amidase (NAAA) is a lysosomal enzyme responsible for hydrolyzing bioactive N‐acylethanolamines—such as anandamide and N‑palmitoylethanolamine—to regulate their local concentrations and, hence, modulate inflammatory and pain‐related signaling. Biochemical studies have demonstrated that NAAA is synthesized as a glycosylated precursor (zymogen) that, under acidic conditions, undergoes a self‐catalyzed proteolytic cleavage into active α‑ and β‑subunits. This cleavage, together with site‐specific N‑glycosylation at several asparagine residues, is critical for the enzyme’s structural stability and full catalytic activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its core enzymatic function, NAAA expression exhibits notable heterogeneity in different cell types. In studies of prostate tissue, NAAA was found to be expressed at relatively high levels in prostate cancer cells, with differences in mRNA splicing yielding both full‐length, catalytically active isoforms and C‑terminally truncated, inactive precursors. Moreover, the enzyme displays a distinct pH-dependent activity profile and partial extracellular secretion, underscoring its potential utility as a tissue biomarker to distinguish aggressive from non-aggressive forms of prostate cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its metabolic functions, aberrant NAAA expression and genetic variations in or near the NAAA gene have been linked to broader aspects of disease. Associations have been identified between NAAA nucleotide sequence variants and conditions such as anorexia nervosa, while bioinformatic analyses reveal correlations between NAAA expression levels, tumor microenvironment modulation, and immune cell infiltration (particularly tumor-associated macrophages). These findings suggest that NAAA not only contributes to lipid signaling regulation but also plays an emerging role in tumor immunity and inflammatory disorders—including autoimmune thyroid disease—thereby representing a potential prognostic biomarker and therapeutic target in cancer immunotherapy."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Li-Ying Zhao, Kazuhito Tsuboi, Yasuo Okamoto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Proteolytic activation and glycosylation of N-acylethanolamine-hydrolyzing acid amidase, a lysosomal enzyme involved in the endocannabinoid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2007.10.002"}], "href": "https://doi.org/10.1016/j.bbalip.2007.10.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17980170"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17980170"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jay M West, Nikolai Zvonok, Kyle M Whitten, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mass spectrometric characterization of human N-acylethanolamine-hydrolyzing acid amidase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Proteome Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/pr200735a"}], "href": "https://doi.org/10.1021/pr200735a"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22040171"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22040171"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Jun Wang, Li-Ying Zhao, Toru Uyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Expression and secretion of N-acylethanolamine-hydrolysing acid amidase in human prostate cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biochem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/jb/mvn122"}], "href": "https://doi.org/10.1093/jb/mvn122"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18806270"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18806270"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Yansheng Liu, Jing Chen, Atul Sethi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycoproteomic analysis of prostate cancer tissues by SWATH mass spectrometry discovers N-acylethanolamine acid amidase and protein tyrosine kinase 7 as signatures for tumor aggressiveness."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Proteomics (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/mcp.M114.038273"}], "href": "https://doi.org/10.1074/mcp.M114.038273"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24741114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24741114"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Yuma Sakura, Kazuhito Tsuboi, Toru Uyama, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A quantitative study on splice variants of N-acylethanolamine acid amidase in human prostate cancer cells and other cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2016.09.018"}], "href": "https://doi.org/10.1016/j.bbalip.2016.09.018"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27693242"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27693242"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Timo Dirk Müller, Kathrin Reichwald, Günter Brönner, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lack of association of genetic variants in genes of the endocannabinoid system with anorexia nervosa."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Child Adolesc Psychiatry Ment Health (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1753-2000-2-33"}], "href": "https://doi.org/10.1186/1753-2000-2-33"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19014633"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19014633"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Dachao Mo, Junjiu Li, Liang Peng, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Polymorphisms on 4q21.1 Contributed to the Risk of Hashimoto's Thyroiditis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genet Test Mol Biomarkers (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1089/gtmb.2019.0125"}], "href": "https://doi.org/10.1089/gtmb.2019.0125"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31750736"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31750736"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Da Huang, Jiayu Shen, Lingyun Zhai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Insights Into the Prognostic Value and Immunological Role of NAAA in Pan-Cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Front Immunol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/fimmu.2021.812713"}], "href": "https://doi.org/10.3389/fimmu.2021.812713"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35069601"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35069601"}]}]}]}
Synonyms	PLT, ASAHL
Proteins	NAAA_HUMAN
NCBI Gene ID	27163
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NAAA has 7,068 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 115 datasets.

Click the + buttons to view associations for NAAA from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

NAAA Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by NAAA gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NAAA gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of NAAA gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of NAAA gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NAAA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of NAAA gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NAAA gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of NAAA gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NAAA gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of NAAA gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of NAAA gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NAAA gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of NAAA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NAAA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NAAA gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NAAA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NAAA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of NAAA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of NAAA gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NAAA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NAAA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NAAA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NAAA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with NAAA protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of NAAA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NAAA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NAAA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NAAA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NAAA protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by NAAA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DGIdb Drug Targets 2026	interacting drugs for NAAA protein from the DGIdb Drug Targets 2026 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NAAA gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with NAAA gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with NAAA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NAAA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NAAA gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of NAAA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NAAA gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing NAAA from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of NAAA gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.