GNE Gene: Bifunctional UDP-GlcNAc 2-Epimerase/ManNAc Kinase
Genetic variants in GNE cause hereditary inclusion body myopathy (HIBM), sialuria, and related neuromuscular disorders.
Gene Information Card
| Symbol | GNE |
|---|---|
| Full Name | Glucosamine (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 10020 ncbi.nlm.nih.gov/gene/10020 |
| Ensembl ID | ENSG00000159921 |
| UniProt ID | Q9Y223 |
| OMIM ID | 603824 |
| HGNC ID | 23657 |
| Aliases | UAE1, GNE10, IBM2, UDP-GlcNAc 2-epimerase/ManNAc kinase |
Description
The GNE gene encodes a bifunctional enzyme that catalyzes the first two committed steps in sialic acid biosynthesis: the epimerization of UDP-N-acetylglucosamine to N-acetylmannosamine (ManNAc) and the subsequent phosphorylation of ManNAc to ManNAc-6-phosphate. This enzyme is rate-limiting for sialic acid production, which is essential for cell surface sialylation. Mutations in GNE lead to a spectrum of disorders, including hereditary inclusion body myopathy (also known as GNE myopathy) and sialuria, with distinct inheritance patterns and molecular mechanisms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hereditary inclusion body myopathy (HIBM) / GNE myopathy | Autosomal recessive mutations cause reduced enzyme activity, leading to hyposialylation of muscle glycoproteins and progressive muscle weakness. | OMIM #605820; ClinVar; multiple publications |
| Sialuria | Autosomal dominant mutations in the allosteric site cause loss of feedback inhibition by CMP-sialic acid, leading to excessive sialic acid production and accumulation. | OMIM #269921; ClinVar |
| Nonaka myopathy (distal myopathy with rimmed vacuoles) | Allelic to HIBM; same GNE mutations cause distal muscle weakness with rimmed vacuoles. | OMIM #605820; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 10.2 | Medium |
| Skeletal Muscle | 8.5 | Medium |
| Kidney | 7.8 | Medium |
| Brain | 6.3 | Low |
| Heart | 5.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 (liver) | 12.1 | High expression |
| A549 (lung) | 8.4 | Medium |
| MCF7 (breast) | 6.2 | Low |
| K562 (leukemia) | 5.0 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| p.Met712Thr (c.2135T>C) | Missense | Common in Japanese HIBM patients | Reduced kinase activity; associated with GNE myopathy |
| p.Val727Met (c.2179G>A) | Missense | Common in Middle Eastern HIBM patients | Reduced epimerase activity; GNE myopathy |
| p.Arg263Gln (c.788G>A) | Missense | Sialuria (dominant) | Loss of feedback inhibition; increased sialic acid production |
| p.Arg266Trp (c.796C>T) | Missense | Sialuria (dominant) | Loss of feedback inhibition; increased sialic acid production |
Mutation functional classification
Loss of Function (LOF)
Recessive mutations in GNE reduce enzyme activity, impairing sialic acid biosynthesis and leading to hyposialylation, which is the primary cause of GNE myopathy.
Gain of Function (GOF)
Dominant mutations in the allosteric site (e.g., Arg263Gln) result in a gain of function by abolishing feedback inhibition, causing excessive sialic acid production in sialuria.
Dominant Negative (DN)
Not typically described for GNE; dominant effects are mainly due to gain-of-function in sialuria, not dominant-negative mechanisms.
View complete mutation data：
Gene Ontology (GO)
| • UDP-N-acetylglucosamine 2-epimerase activity | • N-acetylmannosamine kinase activity |
| • ATP binding | • sialic acid biosynthetic process |
| • carbohydrate phosphorylation | • response to nutrient levels |
Pathways
• Amino sugar and nucleotide sugar metabolism (KEGG: hsa00520)
• Sialic acid biosynthesis (Reactome: R-HSA-4085001)
Protein Summary
The GNE protein is a bifunctional enzyme with an N-terminal epimerase domain and a C-terminal kinase domain. It forms a homodimer and is localized in the cytoplasm. The epimerase domain converts UDP-GlcNAc to ManNAc, and the kinase domain phosphorylates ManNAc to ManNAc-6-phosphate. The enzyme is feedback-inhibited by CMP-sialic acid, the end product of the pathway. Mutations affecting the allosteric site disrupt this regulation, leading to sialuria, while mutations reducing catalytic activity cause GNE myopathy. The protein is ubiquitously expressed but shows higher levels in liver and muscle.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GNE Knockout HEK293 Cell Line | EDJ-KQ6868 | Human | 10020 | Details Get a Quote |
| GNE Knockout HCT 116 Cell Line | EDJ-KQ30076 | Human | 10020 | Details Get a Quote |
| GNE Knockout A-549 Cell Line | EDJ-KQ31449 | Human | 10020 | Details Get a Quote |
| GNE Knockout HeLa Cell Line | EDJ-KQ31451 | Human | 10020 | Details Get a Quote |
