ALG8
Alpha-1,3-Glucosyltransferase: Key Role in N-Glycan Biosynthesis and Congenital Disorders of Glycosylation
Gene Information Card
| Symbol | ALG8 |
|---|---|
| Full Name | ALG8 alpha-1,3-glucosyltransferase |
| Gene Type | Protein coding |
| Chromosomal Location | 11q14.1 |
| NCBI Gene ID | 79053 ncbi.nlm.nih.gov/gene/79053 |
| Ensembl ID | ENSG00000149021 |
| UniProt ID | Q9BVK2 |
| OMIM ID | 608103 |
| HGNC ID | 23161 |
| Aliases | CDG-Ih, DKFZp434B0331, MGC138290, MGC138291 |
Description
The ALG8 gene encodes alpha-1,3-glucosyltransferase, an enzyme localized to the endoplasmic reticulum that catalyzes the addition of the third glucose residue to the dolichol-linked oligosaccharide precursor during N-linked protein glycosylation. This step is critical for proper glycan transfer to nascent proteins. Mutations in ALG8 cause congenital disorder of glycosylation type Ih (CDG-Ih), a multisystem disorder characterized by developmental delay, hypotonia, seizures, and coagulopathy.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Congenital disorder of glycosylation type Ih (CDG-Ih) | Loss-of-function mutations in ALG8 impair the addition of the third glucose to the lipid-linked oligosaccharide, leading to incomplete glycan assembly and defective N-glycosylation of proteins. This results in misfolded proteins and ER stress. | OMIM #608104; ClinVar; multiple case reports (e.g., Chantret et al., 2003; Thiel et al., 2003) |
| ALG8-CDG (CDG-Ih) with liver involvement | Deficient glycosylation of serum proteins and hepatic enzymes causes hepatomegaly, elevated transaminases, and coagulopathy. | ClinVar; case studies (e.g., Morava et al., 2008) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.5 | Medium |
| Pancreas | 10.2 | Medium |
| Kidney | 8.9 | Medium |
| Brain | 6.3 | Low |
| Heart | 5.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 14.8 | Hepatocellular carcinoma cell line; high expression |
| HEK 293 | 9.5 | Embryonic kidney cells; moderate expression |
| K-562 | 7.2 | Leukemia cell line; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1076G>A (p.Arg359His) | Missense | Reported in CDG-Ih patients | Loss of function; reduced enzyme activity |
| c.1090C>T (p.Arg364Trp) | Missense | Reported in CDG-Ih patients | Loss of function; impaired glycosylation |
| c.1A>G (p.Met1Val) | Start loss | Rare | Complete loss of protein expression |
Mutation functional classification
Loss of Function (LOF)
Most ALG8 mutations are loss-of-function, leading to reduced or absent alpha-1,3-glucosyltransferase activity, defective N-glycan assembly, and CDG-Ih phenotype.
Gain of Function (GOF)
No gain-of-function mutations reported in ALG8.
Dominant Negative (DN)
No dominant-negative mutations reported; ALG8-CDG follows autosomal recessive inheritance.
View complete mutation data：
Gene Ontology (GO)
| • GO:0006487 – protein N-linked glycosylation | • GO:0006488 – dolichol-linked oligosaccharide biosynthetic process |
| • GO:0004578 – dolichyl-diphosphooligosaccharide-protein glycotransferase activity | • GO:0016757 – transferase activity |
| • transferring glycosyl groups | • GO:0005789 – endoplasmic reticulum membrane |
Pathways
• N-glycan biosynthesis (Reactome: R-HSA-446203)
• Asparagine N-linked glycosylation (Reactome: R-HSA-446193)
• Congenital disorders of glycosylation (KEGG: hsa00510)
Protein Summary
ALG8 encodes a 526-amino acid transmembrane protein localized to the endoplasmic reticulum membrane. It functions as an alpha-1,3-glucosyltransferase that adds the third glucose residue to the dolichol-P-P-oligosaccharide precursor (Glc3Man9GlcNAc2-PP-dolichol). This step is essential for the proper transfer of the glycan to asparagine residues of nascent polypeptides. The protein contains a C-terminal transmembrane domain and a luminal catalytic domain. Deficiency leads to accumulation of truncated oligosaccharides and congenital disorder of glycosylation type Ih.
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