NEU1

Chr 6AR

neuraminidase 1

Also known as: NANH, NEU, SIAL1

NCBI Gene: 4758 ENSG00000204386 UniProt: Q99519 OMIM: 608272

The encoded protein is a lysosomal neuraminidase that cleaves terminal sialic acid residues from glycoproteins and glycolipids as part of a multienzyme complex with beta-galactosidase and cathepsin A. Mutations cause sialidosis, an autosomal recessive lysosomal storage disease with two forms: type I (late-onset cherry red spot-myoclonus syndrome) and type II (early-onset dysmorphic type with increased severity). The gene shows low constraint to loss-of-function variation, consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

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]

OMIM ResearchGenerating clinical summary…

LOFmechanismARLOEUF 0.842 OMIM phenotypes

Clinical Summary— NEU1

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Gene-Disease Validity (ClinGen)

sialidosis · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

67 unique Pathogenic / Likely Pathogenic· 96 VUS of 356 total submissions

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.84LOEUF

pLI 0.000

Z-score 2.11

OE 0.49 (0.30–0.84)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.42Z-score

OE missense 0.75 (0.66–0.84)

187 obs / 250.3 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.49 (0.30–0.84)

0≤0.351.4

Missense OE?0.75 (0.66–0.84)

0≤0.61.4

Synonymous OE?0.81

0≤1.21.6

LoF obs/exp: 10 / 20.2Missense obs/exp: 187 / 250.3Syn Z: 1.52

ClinVar Variant Classifications

356 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic42

Likely Pathogenic25

VUS96

Likely Benign158

Benign5

Conflicting23

Pathogenic

Likely Pathogenic

VUS

158

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	30	12	0	0	42
Likely Pathogenic	8	17	0	0	25
VUS	1	81	13	1	96
Likely Benign	0	14	43	101	158
Benign	0	1	4	0	5
Conflicting	—				23
Total	39	125	60	102	349

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

View in ClinVar →

8 pathogenic / likely-pathogenic (of 13) ClinVar copy-number / structural variants overlap NEU1 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →