NAGA Gene

Name	N-acetylgalactosaminidase, alpha-
Description	NAGA encodes the lysosomal enzyme alpha-N-acetylgalactosaminidase, which cleaves alpha-N-acetylgalactosaminyl moieties from glycoconjugates. Mutations in NAGA have been identified as the cause of Schindler disease types I and II (type II also known as Kanzaki disease). [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nAlpha‐N‐acetylgalactosaminidase (NAGA) is a lysosomal exoglycosidase that hydrolyzes terminal α‑N‑acetylgalactosamine residues from glycoproteins and glycolipids. Detailed structural studies have revealed its active‐site architecture and substrate‐binding properties, and missense mutations in NAGA have been shown to impair protein folding and stability. Such defects underlie lysosomal storage disorders—including forms of Schindler and Kanzaki diseases—in which diminished NAGA activity leads to substrate accumulation and a broad spectrum of clinical manifestations."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its classical metabolic role, NAGA has emerged as a modulator in tumor biology and immune regulation. Studies in cancer cell lines have shown that tumor‐derived NAGA can deglycosylate key serum proteins—altering the function of vitamin D binding protein and impairing the generation of macrophage-activating factors—thereby contributing to immunosuppression. Increased NAGA activity in advanced melanoma and changes in its expression are associated with alterations in apoptotic and migratory properties of tumor cells, suggesting that NAGA influences tumor progression and metastasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nTherapeutic strategies have exploited NAGA’s biochemical characteristics through protein engineering. Modified forms of NAGA—with altered substrate specificity resembling that of α‑galactosidase A—have been developed as potential enzyme replacement therapies for disorders such as Fabry disease, demonstrating effective clearance of accumulated glycolipids in preclinical models. Moreover, genetic studies have linked increased NAGA expression to neurodevelopmental processes and schizophrenia risk, and efforts to measure its blood levels underscore its emerging role as a biomarker in neurodevelopmental research."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takuro Kanekura, Hitoshi Sakuraba, Fumiko Matsuzawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Three dimensional structural studies of alpha-N-acetylgalactosaminidase (alpha-NAGA) in alpha-NAGA deficiency (Kanzaki disease): different gene mutations cause peculiar structural changes in alpha-NAGAs resulting in different substrate specificities and clinical phenotypes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Dermatol Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jdermsci.2004.09.005"}], "href": "https://doi.org/10.1016/j.jdermsci.2004.09.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15619430"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15619430"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "A Chabás, J Duque, L Gort "}, {"type": "b", "children": [{"type": "t", "text": "A new infantile case of alpha-N-acetylgalactosaminidase deficiency. Cardiomyopathy as a presenting symptom."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Inherit Metab Dis (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10545-006-0470-1"}], "href": "https://doi.org/10.1007/s10545-006-0470-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17171432"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17171432"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Nathaniel E Clark, Scott C Garman "}, {"type": "b", "children": [{"type": "t", "text": "The 1.9 a structure of human alpha-N-acetylgalactosaminidase: The molecular basis of Schindler and Kanzaki diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Biol (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jmb.2009.08.021"}], "href": "https://doi.org/10.1016/j.jmb.2009.08.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19683538"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19683538"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Fedah E Mohamed, Mohammad Al Sorkhy, Mohammad A Ghattas, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A Novel Homozygous Missense Variant in the NAGA Gene with Extreme Intrafamilial Phenotypic Heterogeneity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Mol Neurosci (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12031-019-01398-6"}], "href": "https://doi.org/10.1007/s12031-019-01398-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31468281"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31468281"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Saharuddin B Mohamad, Hideko Nagasawa, Yoshihiro Uto, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tumor cell alpha-N-acetylgalactosaminidase activity and its involvement in GcMAF-related macrophage activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Comp Biochem Physiol A Mol Integr Physiol (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s1095-6433(01)00522-0"}], "href": "https://doi.org/10.1016/s1095-6433(01"}, {"type": "t", "text": "00522-0) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12062184"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12062184"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Marilena Greco, Marianna De Mitri, Fernanda Chiriacò, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Serum proteomic profile of cutaneous malignant melanoma and relation to cancer progression: association to tumor derived alpha-N-acetylgalactosaminidase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2009.04.001"}], "href": "https://doi.org/10.1016/j.canlet.2009.04.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19394758"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19394758"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Mahbube Jafari, Nasibeh Rahimi, Mohammad-Saeid Jami, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of α-N-acetylgalactosaminidase in the gastric cancer cells amplified cell death and attenuated migration, while the multidrug resistance remained unchanged."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Biol Int (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/cbin.11727"}], "href": "https://doi.org/10.1002/cbin.11727"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34816536"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34816536"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Youichi Tajima, Ikuo Kawashima, Takahiro Tsukimura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Use of a modified alpha-N-acetylgalactosaminidase in the development of enzyme replacement therapy for Fabry disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.09.016"}], "href": "https://doi.org/10.1016/j.ajhg.2009.09.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19853240"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19853240"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Ivan B Tomasic, Matthew C Metcalf, Abigail I Guce, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interconversion of the specificities of human lysosomal enzymes associated with Fabry and Schindler diseases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.118588"}], "href": "https://doi.org/10.1074/jbc.M110.118588"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20444686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20444686"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yifan Li, Changguo Ma, Wenqiang Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A missense variant in NDUFA6 confers schizophrenia risk by affecting YY1 binding and NAGA expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Psychiatry (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41380-021-01125-x"}], "href": "https://doi.org/10.1038/s41380-021-01125-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33931730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33931730"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Seda Yılmaz, Pınar Öner "}, {"type": "b", "children": [{"type": "t", "text": "Could low α-N-acetylgalactosaminidase plasma concentration cause schizophrenia?"}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "World J Biol Psychiatry (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/15622975.2022.2070667"}], "href": "https://doi.org/10.1080/15622975.2022.2070667"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35521802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35521802"}]}]}]}
Synonyms	D22S674, GALB
Proteins	NAGAB_HUMAN
NCBI Gene ID	4668
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

NAGA has 5,861 functional associations with biological entities spanning 9 categories (molecular profile, organism, disease, phenotype or trait, chemical, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 117 datasets.

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

If available, associations are ranked by standardized value

Harmonizome 3.0

NAGA Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of NAGA 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 NAGA gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of NAGA 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 NAGA 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 NAGA 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 NAGA 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 NAGA 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 NAGA gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of NAGA 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 NAGA gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with NAGA protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with NAGA 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 NAGA gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of NAGA 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 NAGA gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with NAGA gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of NAGA gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing NAGA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing NAGA protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with NAGA 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 NAGA 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 NAGA gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with NAGA gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with NAGA gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with NAGA gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of NAGA 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 NAGA gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving NAGA gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving NAGA gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with NAGA gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with NAGA 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 NAGA 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 NAGA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with NAGA gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for NAGA protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at NAGA 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 NAGA gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of NAGA 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 NAGA 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 NAGA gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.