NEU4: Sialidase 4 – Key Regulator of Glycoprotein Metabolism and Cancer
Comprehensive genomic and functional analysis of the NEU4 gene, encoding a lysosomal/cytosolic sialidase involved in ganglioside catabolism, neuronal development, and tumor suppression.
Gene Information Card
| Symbol | NEU4 |
|---|---|
| Full Name | Neuraminidase 4 (sialidase 4) |
| Gene Type | Protein coding |
| Chromosomal Location | 2q37.3 |
| NCBI Gene ID | 129807 ncbi.nlm.nih.gov/gene/129807 |
| Ensembl ID | ENSG00000163002 |
| UniProt ID | Q8WWR8 |
| OMIM ID | 608527 |
| HGNC ID | 21328 |
| Aliases | SIAL4, G9, lysosomal sialidase |
Description
NEU4 encodes a member of the sialidase (neuraminidase) family, which catalyzes the removal of terminal sialic acid residues from glycoproteins, glycolipids, and oligosaccharides. The protein localizes to lysosomes and the cytosol, and is involved in ganglioside catabolism, cell signaling, and modulation of cell surface sialylation. NEU4 plays a role in neuronal development, myoblast differentiation, and has been implicated as a tumor suppressor in colorectal cancer and neuroblastoma.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Colorectal cancer | Reduced NEU4 expression leads to increased sialylation of cell surface glycoproteins, promoting tumor cell migration and invasion. | PMID: 20628086; COSMIC mutation data |
| Neuroblastoma | Loss of NEU4 function correlates with enhanced malignant phenotype; re-expression suppresses tumor growth. | PMID: 21930795; ClinVar |
| Sialidosis (type II) | Biallelic mutations in NEU4 cause a mild form of sialidosis with accumulation of sialyloligosaccharides. | OMIM #608527; PMID: 23352259 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Kidney | 6.1 | Low |
| Colon | 4.2 | Low |
| Skeletal muscle | 3.8 | Low |
| Testis | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 9.8 | Reduced in malignant lines |
| HCT116 (colorectal) | 3.5 | Low; associated with poor prognosis |
| MCF7 (breast) | 1.2 | Very low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.544C>T (p.Arg182Trp) | Missense | 0.01% (gnomAD) | Reduced enzymatic activity; associated with sialidosis |
| c.1003G>A (p.Gly335Ser) | Missense | 0.005% | Loss of function; reported in colorectal cancer |
| c.1285_1287del (p.Phe429del) | In-frame deletion | Rare | Impaired lysosomal localization |
| c.1A>G (p.Met1Val) | Start loss | <0.001% | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Missense and deletion mutations (e.g., p.Arg182Trp, p.Gly335Ser) reduce or abolish sialidase activity, leading to accumulation of sialylated substrates and contributing to sialidosis or cancer progression.
Gain of Function (GOF)
No gain-of-function mutations have been reported for NEU4.
Dominant Negative (DN)
No dominant-negative mutations have been described for NEU4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ganglioside metabolism (Reactome: R-HSA-1660662)
• Sialic acid metabolism (KEGG: hsa00520)
• Lysosomal degradation (Reactome: R-HSA-1660499)
Protein Summary
NEU4 (sialidase 4) is a 484-amino acid protein with a molecular weight of ~54 kDa. It contains a conserved sialidase domain and a C-terminal lysosomal targeting motif. The enzyme cleaves terminal sialic acids from glycoconjugates, regulating cell surface sialylation and signaling. NEU4 is expressed in brain, liver, and kidney, and its loss is linked to sialidosis and tumor progression. The protein interacts with gangliosides and glycoproteins, modulating processes such as cell adhesion, migration, and differentiation.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NEU4 Knockout HEK293 Cell Line | EDJ-KQ2623 | Human | 129807 | Details Get a Quote |
| NEU4 Knockout HeLa Cell Line | EDJ-KQ58267 | Human | 129807 | Details Get a Quote |
| NEU4 Knockout A-549 Cell Line | EDJ-KQ66755 | Human | 129807 | Details Get a Quote |
| NEU4 Knockout HCT 116 Cell Line | EDJ-KQ75162 | Human | 129807 | Details Get a Quote |
