ALG2

ALG2

ALG2 is a gene that encodes a protein involved in the process of glycosylation, specifically in the synthesis of N-linked glycoproteins. This gene is part of the ALG (asparagine-linked glycosylation) family, which plays a crucial role in the early steps of the endoplasmic reticulum-based glycosylation pathway.

Function

The ALG2 gene encodes an enzyme known as alpha-1,3/1,6-mannosyltransferase. This enzyme is responsible for adding mannose residues to the growing oligosaccharide chain during the synthesis of N-linked glycoproteins. The process of N-linked glycosylation is essential for proper protein folding, stability, and function.

Pathway

ALG2 is involved in the dolichol-linked oligosaccharide biosynthesis pathway. This pathway is critical for the assembly of the lipid-linked oligosaccharide precursor, which is subsequently transferred to nascent proteins in the endoplasmic reticulum. The ALG2 enzyme specifically catalyzes the addition of mannose residues to the dolichol-linked oligosaccharide, a key step in the formation of the core glycan structure.

Clinical Significance

Mutations in the ALG2 gene can lead to a rare genetic disorder known as Congenital Disorders of Glycosylation (CDG). CDG is a group of inherited metabolic disorders that affect the glycosylation of proteins and lipids. ALG2-CDG, also known as CDG-Ii, is characterized by a wide range of symptoms, including developmental delay, hypotonia, and coagulation disorders.

Symptoms

Patients with ALG2-CDG may present with:

• Developmental delay
• Intellectual disability
• Hypotonia
• Coagulation abnormalities
• Liver dysfunction
• Gastrointestinal issues

Diagnosis

Diagnosis of ALG2-CDG involves a combination of clinical evaluation, biochemical testing, and genetic analysis. Biochemical tests may reveal abnormal glycosylation patterns, while genetic testing can identify mutations in the ALG2 gene.

Treatment

Currently, there is no cure for ALG2-CDG. Treatment is symptomatic and supportive, focusing on managing the individual symptoms and improving the quality of life for affected individuals. This may include physical therapy, nutritional support, and management of coagulation disorders.

Research

Ongoing research is focused on understanding the molecular mechanisms of ALG2 function and its role in glycosylation. Studies are also exploring potential therapeutic approaches, including gene therapy and enzyme replacement therapy, to address the underlying cause of ALG2-CDG.

See Also

• Glycosylation
• Congenital Disorders of Glycosylation
• Endoplasmic Reticulum

External Links

• [GeneCards: ALG2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ALG2)
• [OMIM Entry: ALG2](https://www.omim.org/entry/607905)