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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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NAGA
alpha-N-acetylgalactosaminidase
Chromosome 22 Β· 22q13.2
NCBI Gene: 4668Ensembl: ENSG00000198951.13HGNC: HGNC:7631UniProt: P17050
53PubMed Papers
22Diseases
0Drugs
42Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
extracellular exosomecarbohydrate catabolic processprotein homodimerization activityglycolipid catabolic processalpha-N-acetylgalactosaminidase deficiency type 2alpha-N-acetylgalactosaminidase deficiency type 1alpha-N-acetylgalactosaminidase deficiencyalpha-N-acetylgalactosaminidase deficiency type 3
✦AI Summary

NAGA (alpha-N-acetylgalactosaminidase) is a lysosomal exoglycosidase that removes terminal alpha-N-acetylgalactosamine residues from glycolipids and glycopeptides, playing a critical role in glycolipid catabolism 1. The enzyme functions as a homodimer and operates through a carbohydrate catabolic pathway involving glycoside hydrolysis [GO Annotations]. NAGA shares structural similarity with alpha-galactosidase A (Ξ±-GAL A), including dual active sites capable of binding diverse substrates such as alpha-D-galactose and N-acetyl-D-galactosamine 2. Pathogenic mutations in NAGA cause Schindler disease and Kanzaki disease, rare lysosomal storage disorders characterized by progressive glycolipid accumulation in tissues. Clinically, NAGA has emerged as a promising therapeutic target for Fabry disease; modified NAGA variants demonstrate efficacy as enzyme replacement therapy candidates, suppressing globotriaosylceramide and globotriaosylsphingosine accumulation while avoiding antidrug antibody formation that limits conventional alpha-galactosidase A therapy 1. These properties position NAGA as both a biomarker for storage diseases and a potential therapeutic protein for glycosphingolipidoses.

Sources cited
1
Modified NAGA suppresses glycolipid accumulation and avoids antidrug antibody formation; demonstrates efficacy in animal models of Fabry disease
PMID: 40446427
2
NAGA-related enzyme (GANA-1) possesses dual active sites and can bind multiple substrates including alpha-galactose and N-acetyl-D-galactosamine
PMID: 35694994
⚠Limited data available β€” This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜22
alpha-N-acetylgalactosaminidase deficiency type 2Open Targets
0.80Strong
alpha-N-acetylgalactosaminidase deficiency type 1Open Targets
0.76Strong
alpha-N-acetylgalactosaminidase deficiencyOpen Targets
0.71Strong
alpha-N-acetylgalactosaminidase deficiency type 3Open Targets
0.45Moderate
genetic disorderOpen Targets
0.41Moderate
SeizureOpen Targets
0.37Weak
neurodegenerative diseaseOpen Targets
0.35Weak
Intellectual disabilityOpen Targets
0.16Weak
intelligenceOpen Targets
0.12Weak
arthrogryposis multiplex congenitaOpen Targets
0.12Weak
fetal akinesia deformation sequenceOpen Targets
0.12Weak
fetal akinesia deformation sequence 1Open Targets
0.12Weak
schizophreniaOpen Targets
0.06Suggestive
isolated asymptomatic elevation of creatine phosphokinaseOpen Targets
0.06Suggestive
bipolar disorderOpen Targets
0.06Suggestive
autism spectrum disorderOpen Targets
0.05Suggestive
obsessive-compulsive disorderOpen Targets
0.05Suggestive
pentosuriaOpen Targets
0.04Suggestive
major depressive disorderOpen Targets
0.04Suggestive
attention deficit hyperactivity disorderOpen Targets
0.04Suggestive
Kanzaki diseaseUniProt
Schindler diseaseUniProt
Pathogenic Variants42
NM_000262.3(NAGA):c.759+1_759+8delLikely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 2|Alpha-N-acetylgalactosaminidase deficiency type 1|Alpha-N-acetylgalactosaminidase deficiency type 2;Alpha-N-acetylgalactosaminidase deficiency type 1|Malignant tumor of esophagus
β˜…β˜…β˜†β˜†2025
NM_000262.3(NAGA):c.324+1G>ALikely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1|Alpha-N-acetylgalactosaminidase deficiency type 1;Alpha-N-acetylgalactosaminidase deficiency type 2|Alpha-N-acetylgalactosaminidase deficiency type 1;Alpha-N-acetylgalactosaminidase deficiency type 3;Alpha-N-acetylgalactosaminidase deficiency type 2
β˜…β˜…β˜†β˜†2025
NM_000262.3(NAGA):c.874C>T (p.Gln292Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1|Alpha-N-acetylgalactosaminidase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 292
NM_000262.3(NAGA):c.443G>A (p.Trp148Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1|Alpha-N-acetylgalactosaminidase deficiency
β˜…β˜…β˜†β˜†2025β†’ Residue 148
NM_000262.3(NAGA):c.157C>T (p.Gln53Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1|Alpha-N-acetylgalactosaminidase deficiency type 1;Alpha-N-acetylgalactosaminidase deficiency type 2
β˜…β˜…β˜†β˜†2024β†’ Residue 53
NM_000262.3(NAGA):c.913del (p.Ile305fs)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2026β†’ Residue 305
NM_000262.3(NAGA):c.324del (p.Asp107_Tyr108insTer)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2025β†’ Residue 107
NM_000262.3(NAGA):c.957+2T>CLikely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2025
NM_000262.3(NAGA):c.40C>T (p.Gln14Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency
β˜…β˜†β˜†β˜†2025β†’ Residue 14
NM_000262.3(NAGA):c.667del (p.Trp223fs)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 223
NM_000262.3(NAGA):c.325-1G>CLikely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024
NM_000262.3(NAGA):c.838C>T (p.Leu280Phe)Likely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 280
NM_000262.3(NAGA):c.985C>T (p.Arg329Trp)Likely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 2|Alpha-N-acetylgalactosaminidase deficiency
β˜…β˜†β˜†β˜†2024β†’ Residue 329
NM_000262.3(NAGA):c.190C>T (p.Gln64Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 64
NM_000262.3(NAGA):c.1101+1G>ALikely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 2;Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024
NM_000262.3(NAGA):c.567G>A (p.Trp189Ter)Likely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 2;Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 189
NM_000262.3(NAGA):c.639dup (p.Asn214Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 214
NM_000262.3(NAGA):c.1113dup (p.Tyr372fs)Likely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 2;Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 372
NM_000262.3(NAGA):c.319_322dup (p.Tyr108Ter)Pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2024β†’ Residue 108
NM_000262.3(NAGA):c.324+1G>CLikely pathogenic
Alpha-N-acetylgalactosaminidase deficiency type 1
β˜…β˜†β˜†β˜†2023
View on ClinVar β†—
Related Genes
HEXAProtein interaction94%HEXBProtein interaction94%B3GALT5Protein interaction91%B3GALNT1Protein interaction91%GBGT1Protein interaction90%MAN2B1Protein interaction74%
Tissue Expression6 tissues
Lung
100%
Liver
97%
Heart
69%
Ovary
69%
Bone Marrow
67%
Brain
45%
Gene Interaction Network
Click a node to explore
NAGAHEXAHEXBB3GALT5B3GALNT1GBGT1MAN2B1
PROTEIN STRUCTURE
Preparing viewer…
PDB4DO4 Β· 1.40 Γ… Β· X-ray
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.12LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.87 [0.69–1.12]
RankingsWhere NAGA stands among ~20K protein-coding genes
  • #8,461of 20,598
    Most Researched53
  • #1,493of 5,498
    Most Pathogenic Variants42
  • #11,554of 17,882
    Most Constrained (LOEUF)1.12
Genes detectedNAGA
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
PMID: 30855889
1.00
2
PMID: 29494084
0.90
3
PMID: 30571000
0.80
4
[Schindler-disease/Kanzaki disease].
PMID: 11528921
Ryoikibetsu Shokogun Shirizu Β· 2001
0.70
5
Enzyme replacement therapy using a modified Ξ±-N-acetylgalactosaminidase to suppress progressive glycolipid accumulation and escape from antidrug antibody formation in young human NAGA-transgenic/Gla-knockout mice.
PMID: 40446427
Mol Genet Metab Β· 2025
0.60