NAGA

Chr 22AR

alpha-N-acetylgalactosaminidase

Also known as: D22S674, GALB

NCBI Gene: 4668ENSG00000198951UniProt: P17050

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]

Primary Disease Associations & Inheritance

Kanzaki diseaseMIM #609242
AR
Schindler disease, type IMIM #609241
AR
Schindler disease, type IIIMIM #609241
AR
472
ClinVar variants
73
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— NAGA
🧬
Gene-Disease Validity (ClinGen)
alpha-N-acetylgalactosaminidase deficiency · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
73 Pathogenic / Likely Pathogenic· 131 VUS of 472 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.30LOEUF
pLI 0.000
Z-score 0.51
OE 0.88 (0.61–1.30)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.17Z-score
OE missense 0.97 (0.87–1.08)
237 obs / 244.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.88 (0.61–1.30)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.97 (0.87–1.08)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.88
0≤1.21.6
LoF obs/exp: 18 / 20.5Missense obs/exp: 237 / 244.5Syn Z: 0.90

ClinVar Variant Classifications

472 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic53
Likely Pathogenic20
VUS131
Likely Benign222
Benign32
Conflicting14
53
Pathogenic
20
Likely Pathogenic
131
VUS
222
Likely Benign
32
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
7
0
46
0
53
Likely Pathogenic
11
2
7
0
20
VUS
1
96
33
1
131
Likely Benign
0
1
108
113
222
Benign
0
1
30
1
32
Conflicting
—14
Total19100224115472

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

NAGA · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

NAGA-related Kanzaki disease

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersSkin
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Kanzaki disease

MIM #609242

Molecular basis of disorder known

Autosomal recessive

Schindler disease, type I

MIM #609241

Molecular basis of disorder known

Autosomal recessive

Schindler disease, type III

MIM #609241

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — NAGA
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
A missense variant in NDUFA6 confers schizophrenia risk by affecting YY1 binding and NAGA expression.
Li Y et al.·Mol Psychiatry
2021
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: new mutations and the paradox between genotype and phenotype.
Keulemans JL et al.·J Med Genet
1996Case report
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.
Kanekura T et al.·J Dermatol Sci
2005
A Novel Homozygous Missense Variant in the NAGA Gene with Extreme Intrafamilial Phenotypic Heterogeneity.
Mohamed FE et al.·J Mol Neurosci
2020Case report
Structural and immunocytochemical studies on alpha-N-acetylgalactosaminidase deficiency (Schindler/Kanzaki disease).
Sakuraba H et al.·J Hum Genet
2004
Exploration of Structural and Functional Variations Owing to Point Mutations in α-NAGA.
Meshach Paul D et al.·Interdiscip Sci
2018Functional
Characterization of Streptococcus pneumoniae N-acetylglucosamine-6-phosphate deacetylase as a novel diagnostic marker.
Choi CW et al.·J Microbiol
2013
Human alpha-N-acetylgalactosaminidase (alpha-NAGA) deficiency: no association with neuroaxonal dystrophy?
Bakker HD et al.·Eur J Hum Genet
2001Case report
Whole exome sequencing identifies the potential role of genes involved in p53 pathway in Nasopharyngeal Carcinoma from Northeast India.
Laskar S et al.·Gene
2022
Characterization of gana-1, a Caenorhabditis elegans gene encoding a single ortholog of vertebrate alpha-galactosidase and alpha-N-acetylgalactosaminidase.
Hujová J et al.·BMC Cell Biol
2005
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Characterization and effect of Naga Bhasma on hypoglycemic, antihyperglycemic, and antidiabetic activities in Charles Foster diabetic rats.
Tate P et al.·J Ayurveda Integr Med
2025🔓 Open Access
The deacetylase NagA mediates the remodeling and recycling of peptidoglycan-derived amino sugars in mycobacteria.
Guy CS et al.·J Biol Chem
2025🔓 Open AccessFunctional
AVO reflectivity and pre-stack seismic impedance inversion for gas sand channel detection at South Abu El Naga Field, Onshore Nile Delta, Egypt.
Al-Ashqar NA et al.·Sci Rep
2025🔓 Open Access
Enzyme replacement therapy using a modified α-N-acetylgalactosaminidase to suppress progressive glycolipid accumulation and escape from antidrug antibody formation in young human NAGA-transgenic/Gla-knockout mice.
Sakuraba H et al.·Mol Genet Metab
2025
Rock typing and reservoir characterization of the Messinian Abu Madi Formation in the onshore South Abu El Naga Gas Field, Nile Delta, Egypt.
Al-Shareif AW et al.·Sci Rep
2025🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools