NEU3

Chr 11

neuraminidase 3

Also known as: SIAL3

NCBI Gene: 10825 ENSG00000162139 UniProt: Q9UQ49 OMIM: 604617

NEU3 encodes a plasma membrane-localized sialidase that cleaves sialic acid residues from gangliosides and other glycolipids, regulating membrane ganglioside content and cellular signaling pathways including EGFR signaling. Mutations cause autosomal recessive spastic paraplegia with intellectual disability and seizures, typically presenting in early childhood. The gene shows low constraint to loss-of-function variation (LOEUF 1.34), consistent with recessive inheritance requiring biallelic mutations for disease manifestation.

OMIM ResearchSummary from RefSeq, UniProt

This gene product belongs to a family of glycohydrolytic enzymes which remove sialic acid residues from glycoproteins and glycolipids. It is localized in the plasma membrane, and its activity is specific for gangliosides. It may play a role in modulating the ganglioside content of the lipid bilayer. [provided by RefSeq, Jul 2008]

OMIM ResearchGenerating clinical summary…

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.34

LOEUF

Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.34LOEUF

pLI 0.000

Z-score 0.56

OE 0.85 (0.55–1.34)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

0.10Z-score

OE missense 0.98 (0.89–1.09)

256 obs / 260.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.85 (0.55–1.34)

0≤0.351.4

Missense OE?0.98 (0.89–1.09)

0≤0.61.4

Synonymous OE?1.02

0≤1.21.6

LoF obs/exp: 13 / 15.4Missense obs/exp: 256 / 260.4Syn Z: -0.15

Background carrier burden — how many people carry a rare variant somewhere in NEU3?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 75

732 rare PASS variants

Rare truncating (LoF)

1 in 570

120 rare PASS variants

Rare synonymous (reference)

1 in 270

240 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for NEU3. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 120	1 in 760
South Asian	~43k	1 in 60	1 in 730
Remaining (unassigned)	~30k	1 in 55	1 in 370
European (Finnish)	~27k	1 in 240	≈ 1 in 6,500
Admixed American	~22k	1 in 74	1 in 900
African / African American	~21k	1 in 60	1 in 450
East Asian	~20k	1 in 76	1 in 430
Ashkenazi Jewish	~13k	1 in 240	≈ 1 in 6,300
Middle Eastern	~2,884	1 in 73	1 in 220

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓