ALG14: A Key Gene in Congenital Disorders of Glycosylation
Comprehensive genomic and functional analysis of ALG14, a UDP-N-acetylglucosamine transferase subunit involved in N-linked glycosylation.
Gene Information Card
| Symbol | ALG14 |
|---|---|
| Full Name | ALG14 UDP-N-acetylglucosaminyltransferase subunit |
| Gene Type | Protein coding |
| Chromosomal Location | 1p21.3 |
| NCBI Gene ID | 199857 ncbi.nlm.nih.gov/gene/199857 |
| Ensembl ID | ENSG00000172348 |
| UniProt ID | Q96F25 |
| OMIM ID | 612866 |
| HGNC ID | 28287 |
| Aliases | DKFZp686B2427, FLJ14753, MGC138290, MGC138291 |
Description
ALG14 encodes a subunit of the UDP-N-acetylglucosamine transferase complex, which catalyzes the first step of N-linked glycosylation in the endoplasmic reticulum. This gene is essential for the biosynthesis of lipid-linked oligosaccharides. Mutations in ALG14 cause congenital disorder of glycosylation type I (CDG-I), a multisystem disorder characterized by neurological impairment, developmental delay, and dysmorphic features.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation type I (CDG-I) | Loss-of-function mutations in ALG14 impair the addition of N-acetylglucosamine to dolichol phosphate, disrupting N-glycan assembly. | ClinVar, OMIM |
| Myasthenic syndrome, congenital, 20 (CMS20) | ALG14 mutations lead to defective glycosylation of acetylcholine receptor subunits, causing neuromuscular transmission defects. | ClinVar, OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Liver | 8.3 | Low |
| Heart | 7.1 | Low |
| Kidney | 6.9 | Low |
| Testis | 15.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Moderate expression |
| HeLa | 8.5 | Moderate expression |
| K562 | 6.2 | Low expression |
| HepG2 | 7.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.194G>A (p.Arg65His) | Missense | Rare | Loss of function; associated with CDG-I |
| c.1A>G (p.Met1Val) | Start loss | Rare | Loss of function; associated with CMS20 |
| c.437G>A (p.Arg146Gln) | Missense | Rare | Loss of function; reported in CDG-I |
Mutation functional classification
Loss of Function (LOF)
Most ALG14 mutations are loss-of-function, leading to reduced or absent UDP-N-acetylglucosamine transferase activity.
Gain of Function (GOF)
No gain-of-function mutations reported.
Dominant Negative (DN)
No dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GO:0006486 - protein glycosylation | • GO:0006490 - oligosaccharide-lipid intermediate assembly |
| • GO:0004576 - dolichyl-diphosphooligosaccharide-protein glycotransferase activity | • GO:0005789 - endoplasmic reticulum membrane |
| • GO:0016021 - integral component of membrane |
Pathways
• N-glycan biosynthesis (Reactome: R-HSA-446203)
• Congenital disorders of glycosylation (KEGG: hsa00510)
Protein Summary
ALG14 is a 150-amino acid protein that localizes to the endoplasmic reticulum membrane. It functions as a subunit of the UDP-N-acetylglucosamine transferase complex (ALG13/ALG14), which catalyzes the transfer of N-acetylglucosamine from UDP-GlcNAc to dolichol phosphate. This step is critical for the initiation of N-linked glycosylation. The protein contains a single transmembrane domain and interacts with ALG13.
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