NEU1

Chr 6AR

neuraminidase 1

Also known as: NANH, NEU, SIAL1

NCBI Gene: 4758ENSG00000204386UniProt: Q99519

The protein encoded by this gene is a lysosomal enzyme that cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter is also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis, a lysosomal storage disease that can be type 1 (cherry red spot-myoclonus syndrome or normosomatic type), which is late-onset, or type 2 (the dysmorphic type), which occurs at an earlier age with increased severity. [provided by RefSeq, Jul 2008]

Primary Disease Associations & Inheritance

Sialidosis, type IMIM #256550
AR
Sialidosis, type IIMIM #256550
AR
360
ClinVar variants
75
Pathogenic / LP
0.00
pLI score
1
Active trials
Clinical Summary— NEU1
🧬
Gene-Disease Validity (ClinGen)
sialidosis · 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
75 Pathogenic / Likely Pathogenic· 98 VUS of 360 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.84LOEUF
pLI 0.000
Z-score 2.11
OE 0.49 (0.30–0.84)
Tolerant

Typical tolerance to LoF variation

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.
1.42Z-score
OE missense 0.75 (0.66–0.84)
187 obs / 250.3 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.0.49 (0.30–0.84)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.75 (0.66–0.84)
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.0.81
0≤1.21.6
LoF obs/exp: 10 / 20.2Missense obs/exp: 187 / 250.3Syn Z: 1.52

ClinVar Variant Classifications

360 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic48
Likely Pathogenic27
VUS98
Likely Benign159
Benign5
Conflicting23
48
Pathogenic
27
Likely Pathogenic
98
VUS
159
Likely Benign
5
Benign
23
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
12
18
0
48
Likely Pathogenic
6
17
4
0
27
VUS
1
79
17
1
98
Likely Benign
0
14
44
101
159
Benign
0
1
4
0
5
Conflicting
—23
Total2512387102360

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

View in ClinVar →

Protein Context — Lollipop Plot

NEU1 · protein map & ClinVar variants

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

Gene2Phenotype Curations

NEU1-related sialidosis

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. DisordersEyeSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
NEURAMINIDASE 1; NEU1
MIM #608272 · *

Sialidosis, type I

MIM #256550

Molecular basis of disorder known

Autosomal recessive

Sialidosis, type II

MIM #256550

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Sialidoses.
Franceschetti S et al.·Epileptic Disord
2016Review
Genetic Insights and Clinical Implications of NEU1 Mutations in Sialidosis.
Peng ML et al.·Genes (Basel)
2025Review
Perampanel as precision therapy in rare genetic epilepsies.
Nissenkorn A et al.·Epilepsia
2023
Clinical and electrophysiological characteristics of a type 1 sialidosis patient with a novel deletion mutation in NEU1 gene.
Fan SP et al.·J Formos Med Assoc
2020Review
Proteogenomic analysis of the CALGB 40601 (Alliance) HER2+ breast cancer neoadjuvant trial reveals resistance biomarkers.
Jaehnig EJ et al.·Cell Rep Med
2025Clinical trial
Establishment and characterization of Neu1-knockout zebrafish and its abnormal clinical phenotypes.
Okada K et al.·Biochem J
2020Functional
Progressive myoclonic ataxia as an initial symptom of typical type I sialidosis with NEU1 mutation.
Lin J et al.·Ann Clin Transl Neurol
2024
Oseltamivir enhances 5-FU sensitivity in esophageal squamous carcinoma with high SPNS1.
Yang X et al.·Biomed Pharmacother
2024
Molecular pathology of NEU1 gene in sialidosis.
Seyrantepe V et al.·Hum Mutat
2003Review
Expanding sialidosis spectrum by genome-wide screening: NEU1 mutations in adult-onset myoclonus.
Canafoglia L et al.·Neurology
2014Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Alterations in secondary lipids are associated with neuroinflammation in the brain of Neu1-deficient mice.
Ada E et al.·Cell Tissue Res
2026
Fibroblast-derived NEU1 as a therapeutic target for improving cortical bone integrity and fracture healing.
Wu Y et al.·Theranostics
2026🔓 Open Access
Epididymal epithelial cells facilitate NEU1 loading to modulate sperm α-2,6 sialylation, enhance maturation and motility.
Yi S et al.·Cell Mol Life Sci
2025🔓 Open Access
Prognostic Value and Mechanism of Antibody-Dependent Cellular Cytotoxicity-Related Gene, NEU1, in Oral Squamous Cell Carcinoma.
Zhao W et al.·Cell Biochem Funct
2025Functional
A network pharmacology and in silico approach to target NEU1-mediated microglial activation in neuroinflammation: Validation in an LPS-induced mouse model.
Alzarea SI et al.·Comput Biol Med
2025Functional
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Observational Study

The Natural History of Sialidosis Type I

RECRUITING
NCT06316752National Taiwan University HospitalStarted 2022-03-15
Observational study

External Resources

Links to major genomics databases and tools