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ALG6
ALG6 alpha-1,3-glucosyltransferase
The *ALG6* gene provides instructions for an enzyme essential for glycosylation, a process that attaches sugar molecules to proteins and fats, playing a vital role in cellular function. The *ALG6* gene is responsible for producing alpha-1,3-glucosyltransferase, an enzyme critical for the glycosylation pathway.
ALG6 is located on the short (p) arm of chromosome 1, at band 1p31.3. Arm ratio per GRCh38 - banding schematic.
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Overview
The *ALG6* gene, also known as asparagine-linked glycosylation 6, encodes an enzyme involved in the complex biological process of glycosylation. Glycosylation is crucial for the proper structure and function of many proteins and lipids within the body.
Disruptions in the *ALG6* gene's function can lead to specific inherited conditions, primarily affecting development and neurological health. Understanding this gene is important for diagnosing and managing these rare disorders.
What the gene does
The *ALG6* gene provides instructions for making the enzyme alpha-1,3-glucosyltransferase. This enzyme plays a key role in the glycosylation pathway, a process where sugar molecules (oligosaccharides) are attached to proteins and fats. Glycosylation is a stepwise process; the *ALG6* enzyme specifically adds a glucose molecule to a growing oligosaccharide chain.
Once the correct sequence and number of sugar molecules are linked together, the completed oligosaccharide can then be attached to target proteins or lipids. This modification is essential for proteins to achieve their final functional forms and perform their varied roles within cells, influencing aspects like cell-to-cell communication, immune response, and structural integrity.
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Chromosome location
The *ALG6* gene is located on the short (p) arm of chromosome 1 at position 31.3 (1p31.3). This specific chromosomal address helps geneticists pinpoint its location within the human genome.
Protein structure
Domain architecture has not been experimentally characterised in detail for this protein.
Key variants
Genetic variations within the *ALG6* gene can affect the enzyme's activity, potentially leading to health conditions. These variants include changes that may reduce or eliminate the enzyme's function, impacting the crucial glycosylation process. The clinical significance of any identified variant is typically assessed by healthcare professionals.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.1000delinsGG | p.Leu334fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.100_101del | p.Met34fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.114T>G | p.Tyr38Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.1246_1250del | p.Leu416fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-related disorder |
c.12G>A | p.Trp4Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.1326+1G>A | - | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.136G>T | p.Glu46Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.226dup | p.Thr76fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.658A>T | p.Lys220Ter | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
c.663dup | p.Gly222fs | Pathogenic/Likely pathogenic | ★★☆☆ | ALG6-congenital disorder of glycosylation 1C |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Variants in the *ALG6* gene are associated with ALG6-congenital disorder of glycosylation (ALG6-CDG), also known as congenital disorder of glycosylation type Ic. This condition is an autosomal recessive disorder, meaning an individual must inherit two copies of a pathogenic variant (one from each parent) to develop the condition. It typically involves developmental delay, vision problems, and seizures.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic ALG6 variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The *ALG6* gene is included in several NHS England Genomic Medicine Service approved panels. It is listed with a 'green' status for Congenital disorders of glycosylation, DDG2P, Early onset or syndromic epilepsy, Foetal anomalies (R21), Intellectual disability, Likely inborn error of metabolism (R98), and Undiagnosed metabolic disorders, indicating it is considered clinically actionable for these conditions.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the main function of the ALG6 gene?
The *ALG6* gene provides instructions for an enzyme called alpha-1,3-glucosyltransferase, which is crucial for glycosylation. This process involves adding sugar molecules to proteins and fats, enabling them to function correctly in the body.
What health conditions are associated with variants in the ALG6 gene?
Variants in the *ALG6* gene are associated with ALG6-congenital disorder of glycosylation (ALG6-CDG), also known as congenital disorder of glycosylation type Ic. This condition can lead to developmental delay, vision problems, and seizures.
How is ALG6-CDG inherited?
ALG6-congenital disorder of glycosylation is an autosomal recessive condition. This means that an individual must inherit a pathogenic variant from each parent to be affected by the disorder.
References
- Westphal V, Xiao M, Kwok PY. Identification of a frequent variant in ALG6, the cause of Congenital Disorder of Glycosylation-Ic. Human mutation. 2003. PMID: 14517965
- Grünewald S, Imbach T, Huijben K. Clinical and biochemical characteristics of congenital disorder of glycosylation type Ic, the first recognized endoplasmic reticulum defect in N-glycan synthesis. Annals of neurology. 2000. PMID: 10852543
- Imbach T, Burda P, Kuhnert P. A mutation in the human ortholog of the Saccharomyces cerevisiae ALG6 gene causes carbohydrate-deficient glycoprotein syndrome type-Ic. Proceedings of the National Academy of Sciences of the United States of America. 1999. PMID: 10359825
- Adam MP, Bick S, Mirzaa GM. Congenital Disorders of N-Linked Glycosylation and Multiple Pathway Overview – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY. 1993. PMID: 20301507