NAGPA

Chr 16

N-acetylglucosamine-1-phosphodiester alpha-N-acetylglucosaminidase

Also known as: APAA, UCE

NCBI Gene: 51172ENSG00000103174UniProt: Q9UK23OMIM: 607985

This enzyme catalyzes the second step in forming mannose 6-phosphate targeting signals on lysosomal enzymes by removing N-acetylglucosamine residues from specific sugar moieties. Mutations cause developmental stuttering, with inheritance pattern not clearly established from available data. The gene shows minimal constraint against loss-of-function variants (pLI near zero, LOEUF 1.32), suggesting tolerance to reduced gene dosage.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 1.32
Clinical Summary— NAGPA
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
2 unique Pathogenic / Likely Pathogenic· 69 VUS of 100 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.32LOEUF
pLI 0.000
Z-score 0.43
OE 0.90 (0.63–1.32)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-1.37Z-score
OE missense 1.22 (1.12–1.33)
377 obs / 309.3 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.90 (0.63–1.32)
0≤0.351.4
Missense OE1.22 (1.12–1.33)
0≤0.61.4
Synonymous OE1.39
0≤1.21.6
LoF obs/exp: 19 / 21.2Missense obs/exp: 377 / 309.3Syn Z: -3.61

ClinVar Variant Classifications

100 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic2
VUS69
Likely Benign1
2
Pathogenic
69
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
2
0
2
Likely Pathogenic
0
0
0
0
0
VUS
0
67
2
0
69
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total0684072

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

View in ClinVar →

Protein Context — Lollipop Plot

NAGPA · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients